Contact Dermatitis

Jellyfish stings are one of the most common marine injuries, with an estimated 150 million stings occurring annually worldwide.¹ Most jellyfish stings result in painful localized skin reactions that are self-limited and can be treated with conservative measures including hot water immersion and topical anesthetics. Life-threatening systemic reactions (eg, anaphylaxis, Irukandji syndrome) can occur with some species.^2-4 Mainstream media reports do not reflect the true incidence and variability of jellyfish-related injuries that are commonly encountered in the clinic.³

Characteristics of Jellyfish

There are roughly 10,000 known species of jellyfish, with approximately 100 of them posing danger to humans.⁵ Jellyfish belong to the phylum Cnidaria, which is comprised of 5 classes of both free-floating and sessile animals: Staurozoa (stauromedusae), Hydrozoa (hydroids, fire corals, and Portuguese man-of-war), Scyphozoa (true jellyfish), Anthozoa (corals and sea anemones), and Cubozoa (box jellyfish and Irukandji jellyfish).^1,2,6 Jellyfish typically have several tentacles suspended from a free-floating gelatinous body or bell; these tentacles are covered with thousands of cells unique to Cnidaria called nematocytes or cnidocytes containing specialized stinging organelles known as nematocysts. When triggered by physical (eg, human or foreign-body contact) or chemical stimuli, each nematocyst ejects a hollow filament or barb externally, releasing venom into the victim.^7,8

The scyphozoan, hydrozoan, and cubozoan life cycles generally consist of a bottom-dwelling, sessile polyp form that produces multiple free-swimming ephyrae through an asexual reproductive process called strobilation. These ephyrae grow into the fully mature medusae, recognizable as jellyfish (Figure 1).⁵ Additionally, jellyfish populations experience cycles of temporal and spatial population abundance and crashes known as jellyfish blooms. In 2017, Kaffenberger et al⁹ reviewed the shifting landscape of skin diseases in North America attributable to major changes in climate and weather patterns, including the rise in jellyfish blooms and envenomation outbreaks worldwide (eg, Physalia physalis [Portuguese man-of-war][Figure 2] along the southeastern US coastline, Porpita pacifica off Japanese beaches). Some research suggests jellyfish surges relate to climate change and human interactions with jellyfish habitats by way of eutrophication and fishing (removing predators of jellyfish).^9,10

Clinical Presentation

Jellyfish injuries can vary greatly in clinical symptoms, but they do follow some basic patterns. The severity of pain and symptoms is related to the jellyfish species, the number of stinging cells (nematocysts) that are triggered, and the potency of the venom that is absorbed by the victim.^11-13 Most stings are minor, and patients experience immediate localized pain with serpiginous raised erythematous or urticarial lesions following the distribution of tentacle contact; these lesions have been described as tentaclelike and resembling a string of beads (Figure 3).¹² Pain usually lasts a couple hours, while the skin lesions can last hours to days and can even recur years later. This pattern fits that of the well-known hydrozoans P physalis and Physalia utriculus (bluebottle), which are endemic to the Atlantic and Indo-Pacific Oceans, respectively. The scyphozoan jellyfish causing similar presentations include Pelagia noctiluca (Mauve stinger), Aurelia aurita (Moon jellyfish), and Cyanea species. The cubozoan Chironex fleckeri (Australian box jellyfish or sea wasp) also causes tentaclelike stings but is widely considered the most dangerous jellyfish, as its venom is known to cause cardiac or respiratory arrest.^4,11 More than 100 fatalities have been reported following severe envenomations from C fleckeri in Australian and Indo-Pacific waters.⁶

Stings from another box jellyfish species, Carukia barnesi, cause a unique presentation known as Irukandji syndrome. Carukia barnesi is a small box jellyfish with a bell measuring roughly 2 cm in diameter. It has nematocysts on both its bell and tentacles. It inhabits deeper waters and typically stings divers but also can wash ashore and injure beach tourists. Although Irukandji syndrome usually is associated with C barnesi, which is endemic to Northern Australian beaches, other jellyfish species including P physalis rarely have been linked to this potentially fatal syndrome.^6,11 Unlike the immediate cutaneous and systemic findings described in C fleckeri encounters, symptoms of Irukandji-like stings can be delayed by up to 30 minutes. Patients may present with severe generalized pain (lower back, chest, headache), signs of excess catecholamine release (tachycardia, hypertension, anxiety, diaphoresis, agitation), or cardiopulmonary decompensation (arrhythmia, cardiac arrest, pulmonary edema).^6,11,14.15 Anaphylactic reactions also have been reported in those sensitized by prior stings.¹⁶

Management

Prevention of drowning is key in all marine injuries. Rescuers should remove the individual from the water, establish the ABCs—airway, breathing, and circulation—and seek acute medical attention. If immediate resuscitation is not required, douse the wound as soon as possible with a solution that halts further nematocyst discharge, which may contain alcohol, vinegar, or bicarbonate, depending on the prevalent species. General guidance is available to providers through evidence-based, point-of-care databases including UpToDate and DynaMed, as well as through the American Heart Association (AHA) or a country’s equivalent council on emergency care if residing outside the United States. Pressure immobilization bandages as a means of decreasing venom redistribution is no longer recommended by the AHA because animal studies have shown increased nematocyst discharge after pressure application.¹⁷ As such, touching or applying pressure to the affected area is not recommended until after a proper rinse solution has been applied. Tentacles may be removed mechanically with gloved hands or sand and seawater with minimal compression or agitation.

When acetic acid is appropriate, such as for cubozoan stings, commercially available vinegar (5% acetic acid in the United States) is preferred.^16,17 Tap water can cause discharge of nematocysts, and seawater is preferred when no other solution is available.¹⁸ Most marine venoms are heat labile. Immersion in hot water can produce pain relief, but ice can be just as efficacious and is preferred by some patients. Prior reports of patients stung by Physalia species demonstrated greater pain relief with hot water immersion compared to ice pack application.^18,19

In the setting of anaphylaxis, patients should receive epinephrine and be transported to a hospital with appropriate hemodynamic monitoring and supportive care. If the species of jellyfish has been identified, species-specific antivenin also may be available in certain regions (eg, C fleckeri antivenin manufactured in Australia), but it is unclear if it improves outcomes when compared with supportive care alone.^6,16

Conclusion

Following jellyfish stings, most skin lesions will spontaneously resolve. Patients likely will present days to weeks following the inciting event with mild cutaneous symptoms that are amenable to topical corticosteroids. Recurrent dermatitis following a jellyfish sting is uncommon and is thought to be due to an immunologic mechanism consistent with type IV hypersensitivity reactions. Patients may require multiple courses of treatment before complete resolution.²⁰

Patient education regarding marine envenomation and mechanical barriers such as wetsuits or stinger suits can reduce the risk for injury from jellyfish stings. Sting-inhibiting lotions also are commercially available, though more research is needed.²¹ Many beaches that are known to harbor the dangerous box jellyfish provide stinger nets to direct travelers to safer waters. Complete avoidance during jellyfish season is recommended in highly endemic areas.¹

Jellyfish stings are one of the most common marine injuries, with an estimated 150 million stings occurring annually worldwide.¹ Most jellyfish stings result in painful localized skin reactions that are self-limited and can be treated with conservative measures including hot water immersion and topical anesthetics. Life-threatening systemic reactions (eg, anaphylaxis, Irukandji syndrome) can occur with some species.^2-4 Mainstream media reports do not reflect the true incidence and variability of jellyfish-related injuries that are commonly encountered in the clinic.³

Characteristics of Jellyfish

There are roughly 10,000 known species of jellyfish, with approximately 100 of them posing danger to humans.⁵ Jellyfish belong to the phylum Cnidaria, which is comprised of 5 classes of both free-floating and sessile animals: Staurozoa (stauromedusae), Hydrozoa (hydroids, fire corals, and Portuguese man-of-war), Scyphozoa (true jellyfish), Anthozoa (corals and sea anemones), and Cubozoa (box jellyfish and Irukandji jellyfish).^1,2,6 Jellyfish typically have several tentacles suspended from a free-floating gelatinous body or bell; these tentacles are covered with thousands of cells unique to Cnidaria called nematocytes or cnidocytes containing specialized stinging organelles known as nematocysts. When triggered by physical (eg, human or foreign-body contact) or chemical stimuli, each nematocyst ejects a hollow filament or barb externally, releasing venom into the victim.^7,8

The scyphozoan, hydrozoan, and cubozoan life cycles generally consist of a bottom-dwelling, sessile polyp form that produces multiple free-swimming ephyrae through an asexual reproductive process called strobilation. These ephyrae grow into the fully mature medusae, recognizable as jellyfish (Figure 1).⁵ Additionally, jellyfish populations experience cycles of temporal and spatial population abundance and crashes known as jellyfish blooms. In 2017, Kaffenberger et al⁹ reviewed the shifting landscape of skin diseases in North America attributable to major changes in climate and weather patterns, including the rise in jellyfish blooms and envenomation outbreaks worldwide (eg, Physalia physalis [Portuguese man-of-war][Figure 2] along the southeastern US coastline, Porpita pacifica off Japanese beaches). Some research suggests jellyfish surges relate to climate change and human interactions with jellyfish habitats by way of eutrophication and fishing (removing predators of jellyfish).^9,10

Clinical Presentation

Jellyfish injuries can vary greatly in clinical symptoms, but they do follow some basic patterns. The severity of pain and symptoms is related to the jellyfish species, the number of stinging cells (nematocysts) that are triggered, and the potency of the venom that is absorbed by the victim.^11-13 Most stings are minor, and patients experience immediate localized pain with serpiginous raised erythematous or urticarial lesions following the distribution of tentacle contact; these lesions have been described as tentaclelike and resembling a string of beads (Figure 3).¹² Pain usually lasts a couple hours, while the skin lesions can last hours to days and can even recur years later. This pattern fits that of the well-known hydrozoans P physalis and Physalia utriculus (bluebottle), which are endemic to the Atlantic and Indo-Pacific Oceans, respectively. The scyphozoan jellyfish causing similar presentations include Pelagia noctiluca (Mauve stinger), Aurelia aurita (Moon jellyfish), and Cyanea species. The cubozoan Chironex fleckeri (Australian box jellyfish or sea wasp) also causes tentaclelike stings but is widely considered the most dangerous jellyfish, as its venom is known to cause cardiac or respiratory arrest.^4,11 More than 100 fatalities have been reported following severe envenomations from C fleckeri in Australian and Indo-Pacific waters.⁶

Stings from another box jellyfish species, Carukia barnesi, cause a unique presentation known as Irukandji syndrome. Carukia barnesi is a small box jellyfish with a bell measuring roughly 2 cm in diameter. It has nematocysts on both its bell and tentacles. It inhabits deeper waters and typically stings divers but also can wash ashore and injure beach tourists. Although Irukandji syndrome usually is associated with C barnesi, which is endemic to Northern Australian beaches, other jellyfish species including P physalis rarely have been linked to this potentially fatal syndrome.^6,11 Unlike the immediate cutaneous and systemic findings described in C fleckeri encounters, symptoms of Irukandji-like stings can be delayed by up to 30 minutes. Patients may present with severe generalized pain (lower back, chest, headache), signs of excess catecholamine release (tachycardia, hypertension, anxiety, diaphoresis, agitation), or cardiopulmonary decompensation (arrhythmia, cardiac arrest, pulmonary edema).^6,11,14.15 Anaphylactic reactions also have been reported in those sensitized by prior stings.¹⁶

Management

Prevention of drowning is key in all marine injuries. Rescuers should remove the individual from the water, establish the ABCs—airway, breathing, and circulation—and seek acute medical attention. If immediate resuscitation is not required, douse the wound as soon as possible with a solution that halts further nematocyst discharge, which may contain alcohol, vinegar, or bicarbonate, depending on the prevalent species. General guidance is available to providers through evidence-based, point-of-care databases including UpToDate and DynaMed, as well as through the American Heart Association (AHA) or a country’s equivalent council on emergency care if residing outside the United States. Pressure immobilization bandages as a means of decreasing venom redistribution is no longer recommended by the AHA because animal studies have shown increased nematocyst discharge after pressure application.¹⁷ As such, touching or applying pressure to the affected area is not recommended until after a proper rinse solution has been applied. Tentacles may be removed mechanically with gloved hands or sand and seawater with minimal compression or agitation.

When acetic acid is appropriate, such as for cubozoan stings, commercially available vinegar (5% acetic acid in the United States) is preferred.^16,17 Tap water can cause discharge of nematocysts, and seawater is preferred when no other solution is available.¹⁸ Most marine venoms are heat labile. Immersion in hot water can produce pain relief, but ice can be just as efficacious and is preferred by some patients. Prior reports of patients stung by Physalia species demonstrated greater pain relief with hot water immersion compared to ice pack application.^18,19

In the setting of anaphylaxis, patients should receive epinephrine and be transported to a hospital with appropriate hemodynamic monitoring and supportive care. If the species of jellyfish has been identified, species-specific antivenin also may be available in certain regions (eg, C fleckeri antivenin manufactured in Australia), but it is unclear if it improves outcomes when compared with supportive care alone.^6,16

Conclusion

Following jellyfish stings, most skin lesions will spontaneously resolve. Patients likely will present days to weeks following the inciting event with mild cutaneous symptoms that are amenable to topical corticosteroids. Recurrent dermatitis following a jellyfish sting is uncommon and is thought to be due to an immunologic mechanism consistent with type IV hypersensitivity reactions. Patients may require multiple courses of treatment before complete resolution.²⁰

Patient education regarding marine envenomation and mechanical barriers such as wetsuits or stinger suits can reduce the risk for injury from jellyfish stings. Sting-inhibiting lotions also are commercially available, though more research is needed.²¹ Many beaches that are known to harbor the dangerous box jellyfish provide stinger nets to direct travelers to safer waters. Complete avoidance during jellyfish season is recommended in highly endemic areas.¹

Jellyfish stings are one of the most common marine injuries, with an estimated 150 million stings occurring annually worldwide.¹ Most jellyfish stings result in painful localized skin reactions that are self-limited and can be treated with conservative measures including hot water immersion and topical anesthetics. Life-threatening systemic reactions (eg, anaphylaxis, Irukandji syndrome) can occur with some species.^2-4 Mainstream media reports do not reflect the true incidence and variability of jellyfish-related injuries that are commonly encountered in the clinic.³

Characteristics of Jellyfish

There are roughly 10,000 known species of jellyfish, with approximately 100 of them posing danger to humans.⁵ Jellyfish belong to the phylum Cnidaria, which is comprised of 5 classes of both free-floating and sessile animals: Staurozoa (stauromedusae), Hydrozoa (hydroids, fire corals, and Portuguese man-of-war), Scyphozoa (true jellyfish), Anthozoa (corals and sea anemones), and Cubozoa (box jellyfish and Irukandji jellyfish).^1,2,6 Jellyfish typically have several tentacles suspended from a free-floating gelatinous body or bell; these tentacles are covered with thousands of cells unique to Cnidaria called nematocytes or cnidocytes containing specialized stinging organelles known as nematocysts. When triggered by physical (eg, human or foreign-body contact) or chemical stimuli, each nematocyst ejects a hollow filament or barb externally, releasing venom into the victim.^7,8

The scyphozoan, hydrozoan, and cubozoan life cycles generally consist of a bottom-dwelling, sessile polyp form that produces multiple free-swimming ephyrae through an asexual reproductive process called strobilation. These ephyrae grow into the fully mature medusae, recognizable as jellyfish (Figure 1).⁵ Additionally, jellyfish populations experience cycles of temporal and spatial population abundance and crashes known as jellyfish blooms. In 2017, Kaffenberger et al⁹ reviewed the shifting landscape of skin diseases in North America attributable to major changes in climate and weather patterns, including the rise in jellyfish blooms and envenomation outbreaks worldwide (eg, Physalia physalis [Portuguese man-of-war][Figure 2] along the southeastern US coastline, Porpita pacifica off Japanese beaches). Some research suggests jellyfish surges relate to climate change and human interactions with jellyfish habitats by way of eutrophication and fishing (removing predators of jellyfish).^9,10

Clinical Presentation

Jellyfish injuries can vary greatly in clinical symptoms, but they do follow some basic patterns. The severity of pain and symptoms is related to the jellyfish species, the number of stinging cells (nematocysts) that are triggered, and the potency of the venom that is absorbed by the victim.^11-13 Most stings are minor, and patients experience immediate localized pain with serpiginous raised erythematous or urticarial lesions following the distribution of tentacle contact; these lesions have been described as tentaclelike and resembling a string of beads (Figure 3).¹² Pain usually lasts a couple hours, while the skin lesions can last hours to days and can even recur years later. This pattern fits that of the well-known hydrozoans P physalis and Physalia utriculus (bluebottle), which are endemic to the Atlantic and Indo-Pacific Oceans, respectively. The scyphozoan jellyfish causing similar presentations include Pelagia noctiluca (Mauve stinger), Aurelia aurita (Moon jellyfish), and Cyanea species. The cubozoan Chironex fleckeri (Australian box jellyfish or sea wasp) also causes tentaclelike stings but is widely considered the most dangerous jellyfish, as its venom is known to cause cardiac or respiratory arrest.^4,11 More than 100 fatalities have been reported following severe envenomations from C fleckeri in Australian and Indo-Pacific waters.⁶

Stings from another box jellyfish species, Carukia barnesi, cause a unique presentation known as Irukandji syndrome. Carukia barnesi is a small box jellyfish with a bell measuring roughly 2 cm in diameter. It has nematocysts on both its bell and tentacles. It inhabits deeper waters and typically stings divers but also can wash ashore and injure beach tourists. Although Irukandji syndrome usually is associated with C barnesi, which is endemic to Northern Australian beaches, other jellyfish species including P physalis rarely have been linked to this potentially fatal syndrome.^6,11 Unlike the immediate cutaneous and systemic findings described in C fleckeri encounters, symptoms of Irukandji-like stings can be delayed by up to 30 minutes. Patients may present with severe generalized pain (lower back, chest, headache), signs of excess catecholamine release (tachycardia, hypertension, anxiety, diaphoresis, agitation), or cardiopulmonary decompensation (arrhythmia, cardiac arrest, pulmonary edema).^6,11,14.15 Anaphylactic reactions also have been reported in those sensitized by prior stings.¹⁶

Management

Prevention of drowning is key in all marine injuries. Rescuers should remove the individual from the water, establish the ABCs—airway, breathing, and circulation—and seek acute medical attention. If immediate resuscitation is not required, douse the wound as soon as possible with a solution that halts further nematocyst discharge, which may contain alcohol, vinegar, or bicarbonate, depending on the prevalent species. General guidance is available to providers through evidence-based, point-of-care databases including UpToDate and DynaMed, as well as through the American Heart Association (AHA) or a country’s equivalent council on emergency care if residing outside the United States. Pressure immobilization bandages as a means of decreasing venom redistribution is no longer recommended by the AHA because animal studies have shown increased nematocyst discharge after pressure application.¹⁷ As such, touching or applying pressure to the affected area is not recommended until after a proper rinse solution has been applied. Tentacles may be removed mechanically with gloved hands or sand and seawater with minimal compression or agitation.

When acetic acid is appropriate, such as for cubozoan stings, commercially available vinegar (5% acetic acid in the United States) is preferred.^16,17 Tap water can cause discharge of nematocysts, and seawater is preferred when no other solution is available.¹⁸ Most marine venoms are heat labile. Immersion in hot water can produce pain relief, but ice can be just as efficacious and is preferred by some patients. Prior reports of patients stung by Physalia species demonstrated greater pain relief with hot water immersion compared to ice pack application.^18,19

In the setting of anaphylaxis, patients should receive epinephrine and be transported to a hospital with appropriate hemodynamic monitoring and supportive care. If the species of jellyfish has been identified, species-specific antivenin also may be available in certain regions (eg, C fleckeri antivenin manufactured in Australia), but it is unclear if it improves outcomes when compared with supportive care alone.^6,16

Conclusion

Following jellyfish stings, most skin lesions will spontaneously resolve. Patients likely will present days to weeks following the inciting event with mild cutaneous symptoms that are amenable to topical corticosteroids. Recurrent dermatitis following a jellyfish sting is uncommon and is thought to be due to an immunologic mechanism consistent with type IV hypersensitivity reactions. Patients may require multiple courses of treatment before complete resolution.²⁰

Patient education regarding marine envenomation and mechanical barriers such as wetsuits or stinger suits can reduce the risk for injury from jellyfish stings. Sting-inhibiting lotions also are commercially available, though more research is needed.²¹ Many beaches that are known to harbor the dangerous box jellyfish provide stinger nets to direct travelers to safer waters. Complete avoidance during jellyfish season is recommended in highly endemic areas.¹

Causes of Lepidopterism

Caterpillars are wormlike organisms that serve as the larval stage of moths and butterflies, which belong to the order Lepidoptera. There are almost 165,000 discovered species, with 13,000 found in the United States.^1,2 Roughly 150 species are known to have the potential to cause an adverse reaction in humans, with 50 of these in the United States.¹Lepidopterism describes systemic and cutaneous reactions to moths, butterflies, and caterpillars; erucism describes strictly cutaneous reactions.¹

Although the rate of lepidopterism is thought to be underreported because it often is self-limited and of a mild nature, a review found caterpillars to be the cause of roughly 2.2% of reported bites and stings annually.² Cases increase in number with seasonal increases in caterpillars, which vary by region and species. For example, the Megalopyge opercularis (southern flannel moth) caterpillar was noted to have 2 peaks in a Texas-based study: 12% of reported stings occurred in July; 59% from October through November.³ In general, the likelihood of exposure increases during warmer months, and exposure is more common in people who work outdoors in a rural area or in a suburban area where there are many caterpillar-infested trees.⁴

Most cases of lepidopterism are caused by caterpillars, not by adult butterflies and moths, because the former have many tubular, or porous, hairlike structures called setae that are embedded in the integument. Setae were once thought to be connected to poison-secreting glandular cells, but current belief is that venomous caterpillars lack specialized gland cells and instead produce venom through secretory epithelial cells located above the integument.¹ Venom accumulates in the hemolymph and is stored in the setae or other types of bristles, such as scoli (wartlike bumps that bear setae) or spines.⁵ With a large amount of chitin, bristles have a tendency to fracture and release venom upon contact.¹ It is thought that some species of caterpillars formulate venom by ingesting toxins or toxin precursors from plants; for example, the tiger moth (family Arctiidae) is known to produce venom containing biogenic amines, pyrrolizidine, alkaloids, and cardiac glycosides obtained through food sources.⁵

Even if a caterpillar does not produce venom, its setae might embed into skin or mucous membranes and cause an adverse irritant reaction.¹ Setae also might dislodge and be transported in the air to embed in objects—some remaining stable in the environment for longer than a year.² In contrast to setae, spines are permanently fixed into the integument; for that reason, only direct contact with the caterpillar can result in an adverse reaction. Although it is mostly caterpillars that contain setae and spines, certain species of moths also might contain these structures or might acquire them as they emerge from the cocoon, which often contains incorporated setae.²

Reactions in Humans

Lepidopterism encompasses 3 principal reactions in humans: sting reaction, hypersensitivity reaction, and lonomism (a hemorrhagic diathesis produced by Lonomia caterpillars). The type and severity of the reaction depends on (1) the species of caterpillar or moth and (2) the individual patient.² There are approximately 12 families of caterpillars, mainly of the moth variety, that can cause an adverse reaction in humans.¹ Tables 1 and 2 list examples of species that cause each type of reaction.⁶

Chemicals and toxins contained in the poison of setae and spines vary by species of caterpillar. Numerous kinds have been isolated from different venoms,^1,2 including several peptides, histamine, histamine-releasing substances, acetylcholine, phospholipase A, hyaluronidase, formic acid, proteins with trypsinlike activity, serine proteases such as kallikrein, and other enzymes with vasodegenerative and fibrinolytic properties

Stings: An Immediate Adverse Reaction—Depending on the venom, a sting might result in mild to severe burning pain, accompanied by welts, vesicles, and red papules or plaques.² Figure 1 demonstrates a particularly mild sting from a caterpillar of the family Automeris, examples of which are seen in Figures 2 and 3 and eFigure 1. Components of the venom determine the mechanism of the sting and the pain that accompanies it. For example, a recent study demonstrated that the venom of the Latoia consocia caterpillar induces pain through the ion-channel receptor known as transient receptor potential vanilloid 1, which integrates and sends painful stimuli from the peripheral nervous system to the central nervous system.⁷ It is thought that a variety of ion channels are targets of the venom of caterpillars.

One of the most characteristic sting patterns is that of the caterpillar of family Megalopygidae (flannel moth)(eFigures 2 and 3). The stings of these caterpillars create a unique tram-track pattern of hemorrhagic macules or papules (Figure 4).⁴ A study found that 90% of reported M opercularis envenomations consist primarily of cutaneous symptoms, with 84% of those symptoms being irritation or pain; 45% a puncture or wound; 29% erythema; and 15% edema.³ Systemic findings can include headache, fever, adenopathy, nausea, vomiting, abdominal pain, and chest pain.⁴ Symptoms normally are self-limited, though they can last minutes or hours.

Hypersensitivity Reaction—Studies demonstrate that the symptoms of this reaction are a mixture of type I hypersensitivity, type IV hypersensitivity, and a foreign-body response.² The specific hypersensitivity reaction depends on the venom and the exposed individual—most commonly including a combination of pruritic papules, urticarial wheals, flares, and dermatitis.² A reaction that is a result of direct contact with the caterpillar or moth will appear on exposed areas; however, because setae embed in linens and clothing, they might cause a reaction anywhere on the body. Although usually self-limited, a hypersensitivity reaction might develop within minutes and can last for days or weeks.

Stings and hypersensitivity reactions to caterpillars and moths tend to lead to a nonspecific histologic presentation characterized by epidermal edema and a superficial perivascular lymphocytic infiltrate, often with eosinophils.⁶ After approximately 1 week, a foreign-body response to setae can lead to tuberculoid granulomas accompanied by neutrophils in the dermis and occasionally in subcutaneous tissues (Figures 5 and 6).⁸ If setae have not yet been removed, they also might be visible in skin scrapings.

Additional complications can accompany the hypersensitivity reaction to setae or spines. Type I hypersensitivity reactions can lead to severe reactions on second contact due to previously sensitized IgE antibodies. Although the first reaction appears mild, second contact might result in angioedema, wheezing, dyspnea, or anaphylaxis, or a combination of these findings.⁹ In addition, some patients who come in contact with Dendrolimus caterpillars might develop a condition known as dendrolimiasis, characterized by dermatitis in addition to arthritis or chondritis.⁶ The arthritis is normally monoarticular and can result in complete destruction of the joint. Pararamose, a condition with a similar presentation, is caused by the Brazilian moth Premolis semirufa.⁶

Contact of setae or spines with mucous membranes or inhalation of setae also might result in edema, dysphagia, dyspnea, drooling, rhinitis, or conjunctivitis, or a combination of these findings.⁶ In addition, setae can embed in the eye and cause an inflammatory reaction—ophthalmia nodosa—most commonly caused by caterpillars of the pine processionary moth (Thaumetopoea pityocampa) and characterized by immediate chemosis, which can progress to liquefactive necrosis and hypopyon, later developing into a granulomatous foreign-body response.^2,10 The process is thought to be the result of a combination of the thaumetopoein toxin in the setae and an IgE-mediated response to other proteins.¹⁰

Due to their harpoon shape and forward-only motion, setae might migrate deeper, potentially even to the optic nerve.¹¹ Because migration might take years and the barbed shape of setae does not always allow removal, some patients require lifetime monitoring with slit-lamp examination.Chronic problems, such as cataracts and persistent posterior uveitis, have been reported.^10,11

Lonomism—One of the most serious (though rarest) reactions to caterpillars is lonomism, a condition caused by the caterpillars of Lonomia achelous and Lonomia obliqua moths. These caterpillars have a unique combination of toxins filling their branched spines, which ultimately leads to the same outcome: a hemorrhagic diathesis.

The toxin of L achelous comprises several proteases that degrade fibrin, fibrinogen, and factor XIII while activating prothrombin. In contrast, L obliqua poison causes a hemorrhagic diathesis by promoting a consumptive coagulopathy through enzymes that activate factor X and prothrombin.

With initial contact with either of these Lonomia caterpillars, the patient experiences severe pain accompanied by systemic symptoms, including headache, nausea, and vomiting. Shortly afterward, symptoms of a hemorrhagic diathesis manifest, including bleeding gums, hematuria, bleeding from prior wounds, and epistaxis.⁵ Serious complications of the hemorrhagic diathesis, such as hemorrhage of major organs, leads to death in 4% of patients.⁵ A reported case of a patient whose Lonomia caterpillar sting went unrecognized until a week after the accident ended with progression to stage V chronic renal disease.¹²

Recent research has focused on the specific mechanism of injury caused by Lonomia species. A study found that the venom of L obliqua causes cytoskeleton rearrangement and migration in vascular smooth muscle cells (VSMCs) by inducing formation of reactive oxygen species through activation of nicotinamide adenine dinucleotide phosphate oxidase.¹³ Thus, the venom directly contributes to the proinflammatory phenotype of endothelial cells seen following envenomation. The same study also demonstrated that elevated reactive oxygen species trigger extracellular signal-regulated kinase pathway activation in VSMCs, leading to cell proliferation, re-stenosis, and ischemia.¹³ This finding was confirmed by another study,¹⁴ which demonstrated an increase in Rac1, a signaling protein involved in the extracellular signal-regulated kinase pathway, in VSMCs upon exposure to L obliqua venom. These studies propose potential new targets for treatment to prevent vascular damage.

Reactions to Adult Organisms—Although it is more common for the caterpillar form of these organisms to cause an adverse reaction, the adult moth also might be capable of causing a similar reaction by retaining setae from the cocoon or by their own spines. The most notable example of this is female moths of the genus Hylesia, which possess spines attached to glands on the abdomen. The poison in these spines—a mixture of proteases and chitinase—causes a dermatitis known as Caripito itch—the name derived from a river port in Venezuela where this moth caused a memorable epidemic of moth-induced dermatitis.^7,15 Caripito itch is known for intense pruritus that most commonly lasts days or weeks, possibly longer than 1 year.

Diagnostic Difficulties

The challenge of diagnosing a caterpillar- or moth-induced reaction in humans arises from (1) the lack of clinical history (the caterpillar might not be seen at all by the patient or the examiner) and (2) the similarity of these reactions to those with more common triggers.

When setae remain embedded in the skin or mucous membranes, skin scrapings allow accelerated diagnosis. On a skin scraping prepared with 20% potassium hydroxide, setae appear as tapered and barbed hairlike structures, which allows them to be distinguished from other similar-appearing but differently shaped structures, such as glass fibers.

When setae do not remain embedded in the skin or when the cause of the reaction is due to spines, the physician is left with a nonspecific histologic picture and a large differential diagnosis to be narrowed down based on the history and occasionally the pattern of the skin lesion.

A challenge in sting diagnosis is differentiating a caterpillar or moth sting from that of another organism. In certain cases, such as those of the family Megalopygidae, specific patterns of stings might assist in making the diagnosis. Hypersensitivity reactions are associated with a wider differential diagnosis, including irritant or allergic dermatitis from other causes, scabies, eczema, lichen planus, lichen simplex chronicus, seborrheic dermatitis, and tinea corporis, to name a few.⁶ Skin scrapings can be examined for other features, such as burrows in the case of scabies, to further narrow the differential.

Stings and hypersensitivity reactions lacking a proper history and associated with more severe systemic symptoms have caused misdiagnosis or led to a workup for the wrong condition; for example, the picture of abdominal pain, nausea, vomiting, tachycardia, leukocytosis, hypokalemia, and metabolic acidosis can simulate appendicitis.¹⁶ Upon discovery of a puss caterpillar sting in a patient, her symptoms resolved after treatment with ondansetron, morphine, and intravenous fluids.¹⁶

In lonomism, the diagnosis must be established by laboratory measurement of the fibrinogen level, clotting factors, prothrombin time, and activated partial thromboplastin time.⁴ The differential diagnosis associated with lonomism includes disseminated intravascular coagulation (DIC), snakebite, and a hereditary bleeding disorder.⁴ The combination of laboratory tests and an extensive medical history allows a diagnosis. Absence of a personal or family history of bleeding excludes a diagnosis of hereditary bleeding disorder, whereas the absence of known causes of DIC or thrombocytopenia allows DIC to be excluded from the differential.

Treatment Options and Prevention

Treatment—The first step is to remove any embedded setae from the skin or mucous membranes. The stepwise recommendation is to remove any constricted clothing, detach setae with adhesive tape, wash with soap and water, and dry without touching the skin.¹ Any remaining setae can be removed with additional tape or forceps; setae tend to be fragile and are difficult to remove in their entirety.

Other than removal of the setae, skin reactions are treated symptomatically. Ice packs and isopropyl alcohol have been utilized to cool burning or stinging areas. Pain, pruritus, and inflammation have been alleviated with antihistamines and topical corticosteroids.¹ When pain is severe, oral codeine or local injection of anesthetic can be used. For severe and persistent skin lesions, a course of an oral glucocorticoid can be administered. Intramuscular triamcinolone acetonide has been shown to treat pain, dermatitis, and subcutaneous nodules otherwise refractory to treatment.⁸

Antivenin specific for L obliqua exists to treat lonomism and is therefore effective only when lonomism is caused by that species. Lonomism caused by L achelous is treated with cryoprecipitate, purified fibrinogen, and antifibrinolytic drugs, such as aprotinin.⁶ Whole blood and fresh-frozen plasma have been noted to make hemorrhage worse when utilized to treat lonomism. Because the mechanism of action of the venom of Lonomia species is based, in part, on inducing a proinflammatory profile in endothelial cells, studies have demonstrated that inhibition of kallikrein might prevent vascular injury and thus prevent serious adverse effects, such as renal failure.¹⁷

Prevention—People should wear proper protective clothing when outdoors in potentially infested areas. Measures should be taken to ensure that linens and clothing are not left outside in areas where setae might be carried on the wind. Infestation control is necessary if the population of caterpillars reaches a high enough level.

Conclusion

Several species of caterpillars and moths cause adverse reactions in humans: stings, hypersensitivity reactions, and lonomism. Although most reactions are self-limited, some might have more serious effects, including organ failure and death. Mechanisms of injury vary by species of caterpillar, moth, and butterfly; current research is focused on further defining venom components and signaling pathways to isolate potential targets to aid in the diagnosis and treatment of lepidopterism.

Causes of Lepidopterism

Caterpillars are wormlike organisms that serve as the larval stage of moths and butterflies, which belong to the order Lepidoptera. There are almost 165,000 discovered species, with 13,000 found in the United States.^1,2 Roughly 150 species are known to have the potential to cause an adverse reaction in humans, with 50 of these in the United States.¹Lepidopterism describes systemic and cutaneous reactions to moths, butterflies, and caterpillars; erucism describes strictly cutaneous reactions.¹

Although the rate of lepidopterism is thought to be underreported because it often is self-limited and of a mild nature, a review found caterpillars to be the cause of roughly 2.2% of reported bites and stings annually.² Cases increase in number with seasonal increases in caterpillars, which vary by region and species. For example, the Megalopyge opercularis (southern flannel moth) caterpillar was noted to have 2 peaks in a Texas-based study: 12% of reported stings occurred in July; 59% from October through November.³ In general, the likelihood of exposure increases during warmer months, and exposure is more common in people who work outdoors in a rural area or in a suburban area where there are many caterpillar-infested trees.⁴

Most cases of lepidopterism are caused by caterpillars, not by adult butterflies and moths, because the former have many tubular, or porous, hairlike structures called setae that are embedded in the integument. Setae were once thought to be connected to poison-secreting glandular cells, but current belief is that venomous caterpillars lack specialized gland cells and instead produce venom through secretory epithelial cells located above the integument.¹ Venom accumulates in the hemolymph and is stored in the setae or other types of bristles, such as scoli (wartlike bumps that bear setae) or spines.⁵ With a large amount of chitin, bristles have a tendency to fracture and release venom upon contact.¹ It is thought that some species of caterpillars formulate venom by ingesting toxins or toxin precursors from plants; for example, the tiger moth (family Arctiidae) is known to produce venom containing biogenic amines, pyrrolizidine, alkaloids, and cardiac glycosides obtained through food sources.⁵

Even if a caterpillar does not produce venom, its setae might embed into skin or mucous membranes and cause an adverse irritant reaction.¹ Setae also might dislodge and be transported in the air to embed in objects—some remaining stable in the environment for longer than a year.² In contrast to setae, spines are permanently fixed into the integument; for that reason, only direct contact with the caterpillar can result in an adverse reaction. Although it is mostly caterpillars that contain setae and spines, certain species of moths also might contain these structures or might acquire them as they emerge from the cocoon, which often contains incorporated setae.²

Reactions in Humans

Lepidopterism encompasses 3 principal reactions in humans: sting reaction, hypersensitivity reaction, and lonomism (a hemorrhagic diathesis produced by Lonomia caterpillars). The type and severity of the reaction depends on (1) the species of caterpillar or moth and (2) the individual patient.² There are approximately 12 families of caterpillars, mainly of the moth variety, that can cause an adverse reaction in humans.¹ Tables 1 and 2 list examples of species that cause each type of reaction.⁶

Chemicals and toxins contained in the poison of setae and spines vary by species of caterpillar. Numerous kinds have been isolated from different venoms,^1,2 including several peptides, histamine, histamine-releasing substances, acetylcholine, phospholipase A, hyaluronidase, formic acid, proteins with trypsinlike activity, serine proteases such as kallikrein, and other enzymes with vasodegenerative and fibrinolytic properties

Stings: An Immediate Adverse Reaction—Depending on the venom, a sting might result in mild to severe burning pain, accompanied by welts, vesicles, and red papules or plaques.² Figure 1 demonstrates a particularly mild sting from a caterpillar of the family Automeris, examples of which are seen in Figures 2 and 3 and eFigure 1. Components of the venom determine the mechanism of the sting and the pain that accompanies it. For example, a recent study demonstrated that the venom of the Latoia consocia caterpillar induces pain through the ion-channel receptor known as transient receptor potential vanilloid 1, which integrates and sends painful stimuli from the peripheral nervous system to the central nervous system.⁷ It is thought that a variety of ion channels are targets of the venom of caterpillars.

One of the most characteristic sting patterns is that of the caterpillar of family Megalopygidae (flannel moth)(eFigures 2 and 3). The stings of these caterpillars create a unique tram-track pattern of hemorrhagic macules or papules (Figure 4).⁴ A study found that 90% of reported M opercularis envenomations consist primarily of cutaneous symptoms, with 84% of those symptoms being irritation or pain; 45% a puncture or wound; 29% erythema; and 15% edema.³ Systemic findings can include headache, fever, adenopathy, nausea, vomiting, abdominal pain, and chest pain.⁴ Symptoms normally are self-limited, though they can last minutes or hours.

Hypersensitivity Reaction—Studies demonstrate that the symptoms of this reaction are a mixture of type I hypersensitivity, type IV hypersensitivity, and a foreign-body response.² The specific hypersensitivity reaction depends on the venom and the exposed individual—most commonly including a combination of pruritic papules, urticarial wheals, flares, and dermatitis.² A reaction that is a result of direct contact with the caterpillar or moth will appear on exposed areas; however, because setae embed in linens and clothing, they might cause a reaction anywhere on the body. Although usually self-limited, a hypersensitivity reaction might develop within minutes and can last for days or weeks.

Stings and hypersensitivity reactions to caterpillars and moths tend to lead to a nonspecific histologic presentation characterized by epidermal edema and a superficial perivascular lymphocytic infiltrate, often with eosinophils.⁶ After approximately 1 week, a foreign-body response to setae can lead to tuberculoid granulomas accompanied by neutrophils in the dermis and occasionally in subcutaneous tissues (Figures 5 and 6).⁸ If setae have not yet been removed, they also might be visible in skin scrapings.

Additional complications can accompany the hypersensitivity reaction to setae or spines. Type I hypersensitivity reactions can lead to severe reactions on second contact due to previously sensitized IgE antibodies. Although the first reaction appears mild, second contact might result in angioedema, wheezing, dyspnea, or anaphylaxis, or a combination of these findings.⁹ In addition, some patients who come in contact with Dendrolimus caterpillars might develop a condition known as dendrolimiasis, characterized by dermatitis in addition to arthritis or chondritis.⁶ The arthritis is normally monoarticular and can result in complete destruction of the joint. Pararamose, a condition with a similar presentation, is caused by the Brazilian moth Premolis semirufa.⁶

Contact of setae or spines with mucous membranes or inhalation of setae also might result in edema, dysphagia, dyspnea, drooling, rhinitis, or conjunctivitis, or a combination of these findings.⁶ In addition, setae can embed in the eye and cause an inflammatory reaction—ophthalmia nodosa—most commonly caused by caterpillars of the pine processionary moth (Thaumetopoea pityocampa) and characterized by immediate chemosis, which can progress to liquefactive necrosis and hypopyon, later developing into a granulomatous foreign-body response.^2,10 The process is thought to be the result of a combination of the thaumetopoein toxin in the setae and an IgE-mediated response to other proteins.¹⁰

Due to their harpoon shape and forward-only motion, setae might migrate deeper, potentially even to the optic nerve.¹¹ Because migration might take years and the barbed shape of setae does not always allow removal, some patients require lifetime monitoring with slit-lamp examination.Chronic problems, such as cataracts and persistent posterior uveitis, have been reported.^10,11

Lonomism—One of the most serious (though rarest) reactions to caterpillars is lonomism, a condition caused by the caterpillars of Lonomia achelous and Lonomia obliqua moths. These caterpillars have a unique combination of toxins filling their branched spines, which ultimately leads to the same outcome: a hemorrhagic diathesis.

The toxin of L achelous comprises several proteases that degrade fibrin, fibrinogen, and factor XIII while activating prothrombin. In contrast, L obliqua poison causes a hemorrhagic diathesis by promoting a consumptive coagulopathy through enzymes that activate factor X and prothrombin.

With initial contact with either of these Lonomia caterpillars, the patient experiences severe pain accompanied by systemic symptoms, including headache, nausea, and vomiting. Shortly afterward, symptoms of a hemorrhagic diathesis manifest, including bleeding gums, hematuria, bleeding from prior wounds, and epistaxis.⁵ Serious complications of the hemorrhagic diathesis, such as hemorrhage of major organs, leads to death in 4% of patients.⁵ A reported case of a patient whose Lonomia caterpillar sting went unrecognized until a week after the accident ended with progression to stage V chronic renal disease.¹²

Recent research has focused on the specific mechanism of injury caused by Lonomia species. A study found that the venom of L obliqua causes cytoskeleton rearrangement and migration in vascular smooth muscle cells (VSMCs) by inducing formation of reactive oxygen species through activation of nicotinamide adenine dinucleotide phosphate oxidase.¹³ Thus, the venom directly contributes to the proinflammatory phenotype of endothelial cells seen following envenomation. The same study also demonstrated that elevated reactive oxygen species trigger extracellular signal-regulated kinase pathway activation in VSMCs, leading to cell proliferation, re-stenosis, and ischemia.¹³ This finding was confirmed by another study,¹⁴ which demonstrated an increase in Rac1, a signaling protein involved in the extracellular signal-regulated kinase pathway, in VSMCs upon exposure to L obliqua venom. These studies propose potential new targets for treatment to prevent vascular damage.

Reactions to Adult Organisms—Although it is more common for the caterpillar form of these organisms to cause an adverse reaction, the adult moth also might be capable of causing a similar reaction by retaining setae from the cocoon or by their own spines. The most notable example of this is female moths of the genus Hylesia, which possess spines attached to glands on the abdomen. The poison in these spines—a mixture of proteases and chitinase—causes a dermatitis known as Caripito itch—the name derived from a river port in Venezuela where this moth caused a memorable epidemic of moth-induced dermatitis.^7,15 Caripito itch is known for intense pruritus that most commonly lasts days or weeks, possibly longer than 1 year.

Diagnostic Difficulties

The challenge of diagnosing a caterpillar- or moth-induced reaction in humans arises from (1) the lack of clinical history (the caterpillar might not be seen at all by the patient or the examiner) and (2) the similarity of these reactions to those with more common triggers.

When setae remain embedded in the skin or mucous membranes, skin scrapings allow accelerated diagnosis. On a skin scraping prepared with 20% potassium hydroxide, setae appear as tapered and barbed hairlike structures, which allows them to be distinguished from other similar-appearing but differently shaped structures, such as glass fibers.

When setae do not remain embedded in the skin or when the cause of the reaction is due to spines, the physician is left with a nonspecific histologic picture and a large differential diagnosis to be narrowed down based on the history and occasionally the pattern of the skin lesion.

A challenge in sting diagnosis is differentiating a caterpillar or moth sting from that of another organism. In certain cases, such as those of the family Megalopygidae, specific patterns of stings might assist in making the diagnosis. Hypersensitivity reactions are associated with a wider differential diagnosis, including irritant or allergic dermatitis from other causes, scabies, eczema, lichen planus, lichen simplex chronicus, seborrheic dermatitis, and tinea corporis, to name a few.⁶ Skin scrapings can be examined for other features, such as burrows in the case of scabies, to further narrow the differential.

Stings and hypersensitivity reactions lacking a proper history and associated with more severe systemic symptoms have caused misdiagnosis or led to a workup for the wrong condition; for example, the picture of abdominal pain, nausea, vomiting, tachycardia, leukocytosis, hypokalemia, and metabolic acidosis can simulate appendicitis.¹⁶ Upon discovery of a puss caterpillar sting in a patient, her symptoms resolved after treatment with ondansetron, morphine, and intravenous fluids.¹⁶

In lonomism, the diagnosis must be established by laboratory measurement of the fibrinogen level, clotting factors, prothrombin time, and activated partial thromboplastin time.⁴ The differential diagnosis associated with lonomism includes disseminated intravascular coagulation (DIC), snakebite, and a hereditary bleeding disorder.⁴ The combination of laboratory tests and an extensive medical history allows a diagnosis. Absence of a personal or family history of bleeding excludes a diagnosis of hereditary bleeding disorder, whereas the absence of known causes of DIC or thrombocytopenia allows DIC to be excluded from the differential.

Treatment Options and Prevention

Treatment—The first step is to remove any embedded setae from the skin or mucous membranes. The stepwise recommendation is to remove any constricted clothing, detach setae with adhesive tape, wash with soap and water, and dry without touching the skin.¹ Any remaining setae can be removed with additional tape or forceps; setae tend to be fragile and are difficult to remove in their entirety.

Other than removal of the setae, skin reactions are treated symptomatically. Ice packs and isopropyl alcohol have been utilized to cool burning or stinging areas. Pain, pruritus, and inflammation have been alleviated with antihistamines and topical corticosteroids.¹ When pain is severe, oral codeine or local injection of anesthetic can be used. For severe and persistent skin lesions, a course of an oral glucocorticoid can be administered. Intramuscular triamcinolone acetonide has been shown to treat pain, dermatitis, and subcutaneous nodules otherwise refractory to treatment.⁸

Antivenin specific for L obliqua exists to treat lonomism and is therefore effective only when lonomism is caused by that species. Lonomism caused by L achelous is treated with cryoprecipitate, purified fibrinogen, and antifibrinolytic drugs, such as aprotinin.⁶ Whole blood and fresh-frozen plasma have been noted to make hemorrhage worse when utilized to treat lonomism. Because the mechanism of action of the venom of Lonomia species is based, in part, on inducing a proinflammatory profile in endothelial cells, studies have demonstrated that inhibition of kallikrein might prevent vascular injury and thus prevent serious adverse effects, such as renal failure.¹⁷

Prevention—People should wear proper protective clothing when outdoors in potentially infested areas. Measures should be taken to ensure that linens and clothing are not left outside in areas where setae might be carried on the wind. Infestation control is necessary if the population of caterpillars reaches a high enough level.

Conclusion

Several species of caterpillars and moths cause adverse reactions in humans: stings, hypersensitivity reactions, and lonomism. Although most reactions are self-limited, some might have more serious effects, including organ failure and death. Mechanisms of injury vary by species of caterpillar, moth, and butterfly; current research is focused on further defining venom components and signaling pathways to isolate potential targets to aid in the diagnosis and treatment of lepidopterism.

Causes of Lepidopterism

Caterpillars are wormlike organisms that serve as the larval stage of moths and butterflies, which belong to the order Lepidoptera. There are almost 165,000 discovered species, with 13,000 found in the United States.^1,2 Roughly 150 species are known to have the potential to cause an adverse reaction in humans, with 50 of these in the United States.¹Lepidopterism describes systemic and cutaneous reactions to moths, butterflies, and caterpillars; erucism describes strictly cutaneous reactions.¹

Although the rate of lepidopterism is thought to be underreported because it often is self-limited and of a mild nature, a review found caterpillars to be the cause of roughly 2.2% of reported bites and stings annually.² Cases increase in number with seasonal increases in caterpillars, which vary by region and species. For example, the Megalopyge opercularis (southern flannel moth) caterpillar was noted to have 2 peaks in a Texas-based study: 12% of reported stings occurred in July; 59% from October through November.³ In general, the likelihood of exposure increases during warmer months, and exposure is more common in people who work outdoors in a rural area or in a suburban area where there are many caterpillar-infested trees.⁴

Most cases of lepidopterism are caused by caterpillars, not by adult butterflies and moths, because the former have many tubular, or porous, hairlike structures called setae that are embedded in the integument. Setae were once thought to be connected to poison-secreting glandular cells, but current belief is that venomous caterpillars lack specialized gland cells and instead produce venom through secretory epithelial cells located above the integument.¹ Venom accumulates in the hemolymph and is stored in the setae or other types of bristles, such as scoli (wartlike bumps that bear setae) or spines.⁵ With a large amount of chitin, bristles have a tendency to fracture and release venom upon contact.¹ It is thought that some species of caterpillars formulate venom by ingesting toxins or toxin precursors from plants; for example, the tiger moth (family Arctiidae) is known to produce venom containing biogenic amines, pyrrolizidine, alkaloids, and cardiac glycosides obtained through food sources.⁵

Even if a caterpillar does not produce venom, its setae might embed into skin or mucous membranes and cause an adverse irritant reaction.¹ Setae also might dislodge and be transported in the air to embed in objects—some remaining stable in the environment for longer than a year.² In contrast to setae, spines are permanently fixed into the integument; for that reason, only direct contact with the caterpillar can result in an adverse reaction. Although it is mostly caterpillars that contain setae and spines, certain species of moths also might contain these structures or might acquire them as they emerge from the cocoon, which often contains incorporated setae.²

Reactions in Humans

Lepidopterism encompasses 3 principal reactions in humans: sting reaction, hypersensitivity reaction, and lonomism (a hemorrhagic diathesis produced by Lonomia caterpillars). The type and severity of the reaction depends on (1) the species of caterpillar or moth and (2) the individual patient.² There are approximately 12 families of caterpillars, mainly of the moth variety, that can cause an adverse reaction in humans.¹ Tables 1 and 2 list examples of species that cause each type of reaction.⁶

Chemicals and toxins contained in the poison of setae and spines vary by species of caterpillar. Numerous kinds have been isolated from different venoms,^1,2 including several peptides, histamine, histamine-releasing substances, acetylcholine, phospholipase A, hyaluronidase, formic acid, proteins with trypsinlike activity, serine proteases such as kallikrein, and other enzymes with vasodegenerative and fibrinolytic properties

Stings: An Immediate Adverse Reaction—Depending on the venom, a sting might result in mild to severe burning pain, accompanied by welts, vesicles, and red papules or plaques.² Figure 1 demonstrates a particularly mild sting from a caterpillar of the family Automeris, examples of which are seen in Figures 2 and 3 and eFigure 1. Components of the venom determine the mechanism of the sting and the pain that accompanies it. For example, a recent study demonstrated that the venom of the Latoia consocia caterpillar induces pain through the ion-channel receptor known as transient receptor potential vanilloid 1, which integrates and sends painful stimuli from the peripheral nervous system to the central nervous system.⁷ It is thought that a variety of ion channels are targets of the venom of caterpillars.

One of the most characteristic sting patterns is that of the caterpillar of family Megalopygidae (flannel moth)(eFigures 2 and 3). The stings of these caterpillars create a unique tram-track pattern of hemorrhagic macules or papules (Figure 4).⁴ A study found that 90% of reported M opercularis envenomations consist primarily of cutaneous symptoms, with 84% of those symptoms being irritation or pain; 45% a puncture or wound; 29% erythema; and 15% edema.³ Systemic findings can include headache, fever, adenopathy, nausea, vomiting, abdominal pain, and chest pain.⁴ Symptoms normally are self-limited, though they can last minutes or hours.

Hypersensitivity Reaction—Studies demonstrate that the symptoms of this reaction are a mixture of type I hypersensitivity, type IV hypersensitivity, and a foreign-body response.² The specific hypersensitivity reaction depends on the venom and the exposed individual—most commonly including a combination of pruritic papules, urticarial wheals, flares, and dermatitis.² A reaction that is a result of direct contact with the caterpillar or moth will appear on exposed areas; however, because setae embed in linens and clothing, they might cause a reaction anywhere on the body. Although usually self-limited, a hypersensitivity reaction might develop within minutes and can last for days or weeks.

Stings and hypersensitivity reactions to caterpillars and moths tend to lead to a nonspecific histologic presentation characterized by epidermal edema and a superficial perivascular lymphocytic infiltrate, often with eosinophils.⁶ After approximately 1 week, a foreign-body response to setae can lead to tuberculoid granulomas accompanied by neutrophils in the dermis and occasionally in subcutaneous tissues (Figures 5 and 6).⁸ If setae have not yet been removed, they also might be visible in skin scrapings.

Additional complications can accompany the hypersensitivity reaction to setae or spines. Type I hypersensitivity reactions can lead to severe reactions on second contact due to previously sensitized IgE antibodies. Although the first reaction appears mild, second contact might result in angioedema, wheezing, dyspnea, or anaphylaxis, or a combination of these findings.⁹ In addition, some patients who come in contact with Dendrolimus caterpillars might develop a condition known as dendrolimiasis, characterized by dermatitis in addition to arthritis or chondritis.⁶ The arthritis is normally monoarticular and can result in complete destruction of the joint. Pararamose, a condition with a similar presentation, is caused by the Brazilian moth Premolis semirufa.⁶

Contact of setae or spines with mucous membranes or inhalation of setae also might result in edema, dysphagia, dyspnea, drooling, rhinitis, or conjunctivitis, or a combination of these findings.⁶ In addition, setae can embed in the eye and cause an inflammatory reaction—ophthalmia nodosa—most commonly caused by caterpillars of the pine processionary moth (Thaumetopoea pityocampa) and characterized by immediate chemosis, which can progress to liquefactive necrosis and hypopyon, later developing into a granulomatous foreign-body response.^2,10 The process is thought to be the result of a combination of the thaumetopoein toxin in the setae and an IgE-mediated response to other proteins.¹⁰

Due to their harpoon shape and forward-only motion, setae might migrate deeper, potentially even to the optic nerve.¹¹ Because migration might take years and the barbed shape of setae does not always allow removal, some patients require lifetime monitoring with slit-lamp examination.Chronic problems, such as cataracts and persistent posterior uveitis, have been reported.^10,11

Lonomism—One of the most serious (though rarest) reactions to caterpillars is lonomism, a condition caused by the caterpillars of Lonomia achelous and Lonomia obliqua moths. These caterpillars have a unique combination of toxins filling their branched spines, which ultimately leads to the same outcome: a hemorrhagic diathesis.

The toxin of L achelous comprises several proteases that degrade fibrin, fibrinogen, and factor XIII while activating prothrombin. In contrast, L obliqua poison causes a hemorrhagic diathesis by promoting a consumptive coagulopathy through enzymes that activate factor X and prothrombin.

With initial contact with either of these Lonomia caterpillars, the patient experiences severe pain accompanied by systemic symptoms, including headache, nausea, and vomiting. Shortly afterward, symptoms of a hemorrhagic diathesis manifest, including bleeding gums, hematuria, bleeding from prior wounds, and epistaxis.⁵ Serious complications of the hemorrhagic diathesis, such as hemorrhage of major organs, leads to death in 4% of patients.⁵ A reported case of a patient whose Lonomia caterpillar sting went unrecognized until a week after the accident ended with progression to stage V chronic renal disease.¹²

Recent research has focused on the specific mechanism of injury caused by Lonomia species. A study found that the venom of L obliqua causes cytoskeleton rearrangement and migration in vascular smooth muscle cells (VSMCs) by inducing formation of reactive oxygen species through activation of nicotinamide adenine dinucleotide phosphate oxidase.¹³ Thus, the venom directly contributes to the proinflammatory phenotype of endothelial cells seen following envenomation. The same study also demonstrated that elevated reactive oxygen species trigger extracellular signal-regulated kinase pathway activation in VSMCs, leading to cell proliferation, re-stenosis, and ischemia.¹³ This finding was confirmed by another study,¹⁴ which demonstrated an increase in Rac1, a signaling protein involved in the extracellular signal-regulated kinase pathway, in VSMCs upon exposure to L obliqua venom. These studies propose potential new targets for treatment to prevent vascular damage.

Reactions to Adult Organisms—Although it is more common for the caterpillar form of these organisms to cause an adverse reaction, the adult moth also might be capable of causing a similar reaction by retaining setae from the cocoon or by their own spines. The most notable example of this is female moths of the genus Hylesia, which possess spines attached to glands on the abdomen. The poison in these spines—a mixture of proteases and chitinase—causes a dermatitis known as Caripito itch—the name derived from a river port in Venezuela where this moth caused a memorable epidemic of moth-induced dermatitis.^7,15 Caripito itch is known for intense pruritus that most commonly lasts days or weeks, possibly longer than 1 year.

Diagnostic Difficulties

The challenge of diagnosing a caterpillar- or moth-induced reaction in humans arises from (1) the lack of clinical history (the caterpillar might not be seen at all by the patient or the examiner) and (2) the similarity of these reactions to those with more common triggers.

When setae remain embedded in the skin or mucous membranes, skin scrapings allow accelerated diagnosis. On a skin scraping prepared with 20% potassium hydroxide, setae appear as tapered and barbed hairlike structures, which allows them to be distinguished from other similar-appearing but differently shaped structures, such as glass fibers.

When setae do not remain embedded in the skin or when the cause of the reaction is due to spines, the physician is left with a nonspecific histologic picture and a large differential diagnosis to be narrowed down based on the history and occasionally the pattern of the skin lesion.

A challenge in sting diagnosis is differentiating a caterpillar or moth sting from that of another organism. In certain cases, such as those of the family Megalopygidae, specific patterns of stings might assist in making the diagnosis. Hypersensitivity reactions are associated with a wider differential diagnosis, including irritant or allergic dermatitis from other causes, scabies, eczema, lichen planus, lichen simplex chronicus, seborrheic dermatitis, and tinea corporis, to name a few.⁶ Skin scrapings can be examined for other features, such as burrows in the case of scabies, to further narrow the differential.

Stings and hypersensitivity reactions lacking a proper history and associated with more severe systemic symptoms have caused misdiagnosis or led to a workup for the wrong condition; for example, the picture of abdominal pain, nausea, vomiting, tachycardia, leukocytosis, hypokalemia, and metabolic acidosis can simulate appendicitis.¹⁶ Upon discovery of a puss caterpillar sting in a patient, her symptoms resolved after treatment with ondansetron, morphine, and intravenous fluids.¹⁶

In lonomism, the diagnosis must be established by laboratory measurement of the fibrinogen level, clotting factors, prothrombin time, and activated partial thromboplastin time.⁴ The differential diagnosis associated with lonomism includes disseminated intravascular coagulation (DIC), snakebite, and a hereditary bleeding disorder.⁴ The combination of laboratory tests and an extensive medical history allows a diagnosis. Absence of a personal or family history of bleeding excludes a diagnosis of hereditary bleeding disorder, whereas the absence of known causes of DIC or thrombocytopenia allows DIC to be excluded from the differential.

Treatment Options and Prevention

Treatment—The first step is to remove any embedded setae from the skin or mucous membranes. The stepwise recommendation is to remove any constricted clothing, detach setae with adhesive tape, wash with soap and water, and dry without touching the skin.¹ Any remaining setae can be removed with additional tape or forceps; setae tend to be fragile and are difficult to remove in their entirety.

Other than removal of the setae, skin reactions are treated symptomatically. Ice packs and isopropyl alcohol have been utilized to cool burning or stinging areas. Pain, pruritus, and inflammation have been alleviated with antihistamines and topical corticosteroids.¹ When pain is severe, oral codeine or local injection of anesthetic can be used. For severe and persistent skin lesions, a course of an oral glucocorticoid can be administered. Intramuscular triamcinolone acetonide has been shown to treat pain, dermatitis, and subcutaneous nodules otherwise refractory to treatment.⁸

Antivenin specific for L obliqua exists to treat lonomism and is therefore effective only when lonomism is caused by that species. Lonomism caused by L achelous is treated with cryoprecipitate, purified fibrinogen, and antifibrinolytic drugs, such as aprotinin.⁶ Whole blood and fresh-frozen plasma have been noted to make hemorrhage worse when utilized to treat lonomism. Because the mechanism of action of the venom of Lonomia species is based, in part, on inducing a proinflammatory profile in endothelial cells, studies have demonstrated that inhibition of kallikrein might prevent vascular injury and thus prevent serious adverse effects, such as renal failure.¹⁷

Prevention—People should wear proper protective clothing when outdoors in potentially infested areas. Measures should be taken to ensure that linens and clothing are not left outside in areas where setae might be carried on the wind. Infestation control is necessary if the population of caterpillars reaches a high enough level.

Conclusion

Several species of caterpillars and moths cause adverse reactions in humans: stings, hypersensitivity reactions, and lonomism. Although most reactions are self-limited, some might have more serious effects, including organ failure and death. Mechanisms of injury vary by species of caterpillar, moth, and butterfly; current research is focused on further defining venom components and signaling pathways to isolate potential targets to aid in the diagnosis and treatment of lepidopterism.

Despite the clinical value of medical devices, there is a potential for these products to cause adverse skin reactions in some patients. Findings from a European retrospective study, published in the European Journal of Allergy and Clinical Immunology, show that nearly one-quarter of patients with suspected allergic contact dermatitis were referred for patch testing for contact allergies associated with medical devices, highlighting the possibility of a high prevalence of contact allergens in these devices.

“We found it important to publish these findings, because up until now no clear figures have been reported regarding this particular clinical problem,” said study author Olivier Aerts, MD, a researcher in the contact allergy unit at the University Hospital Antwerp, Belgium, in an interview with this news organization.

For the study, Dr. Aerts and colleagues conducted a retrospective analysis of medical device users with suspected allergic contact dermatitis. All patients had been patch tested at a tertiary European clinic between 2018 and 2020.

The cohort included patients who experienced suspected contact allergy from medical adhesives (n = 57), gloves (n = 38), topical and surface medical devices (n = 38), glucose sensors and insulin pumps (n = 74), and prostheses (n = 75). Other medical products associated with contact allergy in another 44 patients included surgical glues, face masks, compression stockings, condoms, and suture materials.

Overall, 326 patients had been patch-tested during the 30-month study period. Approximately 25.8% of all patients – including 299 adults and 27 children – were referred for contact allergy associated with medical devices.

Acrylates were the most frequently encountered contact allergens and were found in diabetes devices and medical adhesives. Potential skin sensitizers included colophonium-related substances, D-limonene, isothiazolinone derivatives, salicylates, and sulphites, all of which were identified across most products.

According to the investigators, many of the labels for the medical devices made no mention of the potential skin sensitizers, except in the cases of some topical and surface disinfectants. And many topical products are often marketed as medical devices rather than cosmetics, further complicating labeling issues, according to Dr. Aerts.

“What should be done to help any patient suffering from allergic contact due to medical devices is that these devices should be labeled with all their components, or at the very least with the potential skin sensitizers these may contain,” Dr. Aerts explained. He added that manufacturers should “establish more cooperation with physicians/dermatologists who evaluate such patients,” a cooperation that often exists with cosmetic companies.

Dr. Aerts noted that while it’s important for patch testers and dermatologists to be aware of the prevalence of allergic contact dermatitis in medical device users, companies producing these devices should also be aware of these potential issues. “Additionally, legislators/regulators should perhaps focus some more on the cutaneous side effects these products may provoke,” he said, “as this awareness may hopefully also serve as a stimulant to perform more clinical allergy research in this field.”

Leonard Bielory, MD, an allergist at Robert Wood Johnson University Hospital in Rahway, New Jersey, told this news organization that the findings are “alarming” and should heighten clinicians’ awareness of the possibility of allergic contact dermatitis among medical device users.

Dr. Bielory, who wasn’t involved in the research, noted that the findings from this study may not be entirely generalizable to the U.S., given the study was performed in Europe. “In contrast to other countries, the U.S. is very conscientious about allergic responses to items being used in hospitals,” he added, “or such that the issue here is that many of these things would be an adverse reaction, which you have to report.” He suggested that further research in this field is needed to determine the prevalence of possible skin sensitizers in products specifically developed and marketed in the U.S.

The study had no specific funding. Dr. Aerts and Dr. Bielory have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Despite the clinical value of medical devices, there is a potential for these products to cause adverse skin reactions in some patients. Findings from a European retrospective study, published in the European Journal of Allergy and Clinical Immunology, show that nearly one-quarter of patients with suspected allergic contact dermatitis were referred for patch testing for contact allergies associated with medical devices, highlighting the possibility of a high prevalence of contact allergens in these devices.

“We found it important to publish these findings, because up until now no clear figures have been reported regarding this particular clinical problem,” said study author Olivier Aerts, MD, a researcher in the contact allergy unit at the University Hospital Antwerp, Belgium, in an interview with this news organization.

For the study, Dr. Aerts and colleagues conducted a retrospective analysis of medical device users with suspected allergic contact dermatitis. All patients had been patch tested at a tertiary European clinic between 2018 and 2020.

The cohort included patients who experienced suspected contact allergy from medical adhesives (n = 57), gloves (n = 38), topical and surface medical devices (n = 38), glucose sensors and insulin pumps (n = 74), and prostheses (n = 75). Other medical products associated with contact allergy in another 44 patients included surgical glues, face masks, compression stockings, condoms, and suture materials.

Overall, 326 patients had been patch-tested during the 30-month study period. Approximately 25.8% of all patients – including 299 adults and 27 children – were referred for contact allergy associated with medical devices.

Acrylates were the most frequently encountered contact allergens and were found in diabetes devices and medical adhesives. Potential skin sensitizers included colophonium-related substances, D-limonene, isothiazolinone derivatives, salicylates, and sulphites, all of which were identified across most products.

According to the investigators, many of the labels for the medical devices made no mention of the potential skin sensitizers, except in the cases of some topical and surface disinfectants. And many topical products are often marketed as medical devices rather than cosmetics, further complicating labeling issues, according to Dr. Aerts.

“What should be done to help any patient suffering from allergic contact due to medical devices is that these devices should be labeled with all their components, or at the very least with the potential skin sensitizers these may contain,” Dr. Aerts explained. He added that manufacturers should “establish more cooperation with physicians/dermatologists who evaluate such patients,” a cooperation that often exists with cosmetic companies.

Dr. Aerts noted that while it’s important for patch testers and dermatologists to be aware of the prevalence of allergic contact dermatitis in medical device users, companies producing these devices should also be aware of these potential issues. “Additionally, legislators/regulators should perhaps focus some more on the cutaneous side effects these products may provoke,” he said, “as this awareness may hopefully also serve as a stimulant to perform more clinical allergy research in this field.”

Leonard Bielory, MD, an allergist at Robert Wood Johnson University Hospital in Rahway, New Jersey, told this news organization that the findings are “alarming” and should heighten clinicians’ awareness of the possibility of allergic contact dermatitis among medical device users.

Dr. Bielory, who wasn’t involved in the research, noted that the findings from this study may not be entirely generalizable to the U.S., given the study was performed in Europe. “In contrast to other countries, the U.S. is very conscientious about allergic responses to items being used in hospitals,” he added, “or such that the issue here is that many of these things would be an adverse reaction, which you have to report.” He suggested that further research in this field is needed to determine the prevalence of possible skin sensitizers in products specifically developed and marketed in the U.S.

The study had no specific funding. Dr. Aerts and Dr. Bielory have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Despite the clinical value of medical devices, there is a potential for these products to cause adverse skin reactions in some patients. Findings from a European retrospective study, published in the European Journal of Allergy and Clinical Immunology, show that nearly one-quarter of patients with suspected allergic contact dermatitis were referred for patch testing for contact allergies associated with medical devices, highlighting the possibility of a high prevalence of contact allergens in these devices.

“We found it important to publish these findings, because up until now no clear figures have been reported regarding this particular clinical problem,” said study author Olivier Aerts, MD, a researcher in the contact allergy unit at the University Hospital Antwerp, Belgium, in an interview with this news organization.

For the study, Dr. Aerts and colleagues conducted a retrospective analysis of medical device users with suspected allergic contact dermatitis. All patients had been patch tested at a tertiary European clinic between 2018 and 2020.

The cohort included patients who experienced suspected contact allergy from medical adhesives (n = 57), gloves (n = 38), topical and surface medical devices (n = 38), glucose sensors and insulin pumps (n = 74), and prostheses (n = 75). Other medical products associated with contact allergy in another 44 patients included surgical glues, face masks, compression stockings, condoms, and suture materials.

Overall, 326 patients had been patch-tested during the 30-month study period. Approximately 25.8% of all patients – including 299 adults and 27 children – were referred for contact allergy associated with medical devices.

Acrylates were the most frequently encountered contact allergens and were found in diabetes devices and medical adhesives. Potential skin sensitizers included colophonium-related substances, D-limonene, isothiazolinone derivatives, salicylates, and sulphites, all of which were identified across most products.

According to the investigators, many of the labels for the medical devices made no mention of the potential skin sensitizers, except in the cases of some topical and surface disinfectants. And many topical products are often marketed as medical devices rather than cosmetics, further complicating labeling issues, according to Dr. Aerts.

“What should be done to help any patient suffering from allergic contact due to medical devices is that these devices should be labeled with all their components, or at the very least with the potential skin sensitizers these may contain,” Dr. Aerts explained. He added that manufacturers should “establish more cooperation with physicians/dermatologists who evaluate such patients,” a cooperation that often exists with cosmetic companies.

Dr. Aerts noted that while it’s important for patch testers and dermatologists to be aware of the prevalence of allergic contact dermatitis in medical device users, companies producing these devices should also be aware of these potential issues. “Additionally, legislators/regulators should perhaps focus some more on the cutaneous side effects these products may provoke,” he said, “as this awareness may hopefully also serve as a stimulant to perform more clinical allergy research in this field.”

Leonard Bielory, MD, an allergist at Robert Wood Johnson University Hospital in Rahway, New Jersey, told this news organization that the findings are “alarming” and should heighten clinicians’ awareness of the possibility of allergic contact dermatitis among medical device users.

Dr. Bielory, who wasn’t involved in the research, noted that the findings from this study may not be entirely generalizable to the U.S., given the study was performed in Europe. “In contrast to other countries, the U.S. is very conscientious about allergic responses to items being used in hospitals,” he added, “or such that the issue here is that many of these things would be an adverse reaction, which you have to report.” He suggested that further research in this field is needed to determine the prevalence of possible skin sensitizers in products specifically developed and marketed in the U.S.

The study had no specific funding. Dr. Aerts and Dr. Bielory have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Topical medications frequently are prescribed in dermatology and provide the advantages of direct skin penetration and targeted application while typically sparing patients from systemic effects. Adverse cutaneous effects include allergic contact dermatitis (ACD), irritant contact dermatitis (ICD), photosensitivity, urticaria, hyperpigmentation or hypopigmentation, atrophy, periorificial dermatitis, and acneform eruptions. Allergic contact dermatitis can develop from the active drug or vehicle components.

Patients with medicament ACD often present with symptoms of pruritus and dermatitis at the site of topical application. They may express concern that the medication is no longer working or seems to be making things worse. Certain sites are more prone to developing medicament dermatitis, including the face, groin, and lower legs. Older adults may be more at risk. Other risk factors include pre-existing skin diseases such as stasis dermatitis, acne, psoriasis, atopic dermatitis, and genital dermatoses.¹ A review of 14,911 patch-tested patients from a single referral clinic revealed that 17.4% had iatrogenic contact dermatitis, with the most common culprits being topical antibiotics, antiseptics, and steroids.²

In this 2-part series, we will focus on the active drug as a source of ACD. Part 1 explores ACD associated with acne and rosacea medications, antimicrobials, antihistamines, and topical pain preparations.

Acne and Rosacea Medications

Retinoids—Topical retinoids are first-line acne treatments that help normalize skin keratinization. Irritant contact dermatitis from retinoids is a well-known and common side effect. Although far less common than ICD, ACD from topical retinoid use has been reported.^3,4 Reactions to tretinoin are most frequently reported in the literature compared to adapalene gel⁵ and tazarotene foam, which have lower potential for sensitization.⁶ Allergic contact dermatitis also has been reported from retinyl palmitate^7,8 in cosmetic creams and from occupational exposure in settings of industrial vitamin A production.⁹ Both ICD and ACD from topical retinoids can present with pruritus, erythema, and scaling. Given this clinical overlap between ACD and ICD, patch testing is crucial in differentiating the underlying etiology of the dermatitis.

Benzoyl Peroxide—Benzoyl peroxide (BP) is another popular topical acne treatment that targets Cutibacterium acnes, a bacterium often implicated in the pathogenesis of acne vulgaris. Similar to retinoids, ICD is more common than ACD. Several cases of ACD to BP have been reported.^10-14 Occasionally, honey-colored crusting associated with ACD to BP can mimic impetigo.¹⁰ Aside from use of BP as an acne treatment, other potential exposures to BP include bleached flour¹³ and orthopedic bone cement. Occupations at risk for potential BP exposure include dental technicians¹⁵ and those working in plastic manufacturing.

Brimonidine—Brimonidine tartrate is a selective α₂-adrenergic agonist initially used to treat open-angle glaucoma and also is used as a topical treatment for rosacea. Allergic reactions to brimonidine eye drops may present with periorbital hyperpigmentation and pruritic bullous lesions.¹⁶ Case reports of topical brimonidine ACD have demonstrated mixed patch test results, with positive patch tests to Mirvaso (Galderma) as is but negative patch tests to pure brimonidine tartrate 0.33%.^17,18 Ringuet and Houle¹⁹ reported the first known positive patch test reaction to pure topical brimonidine, testing with brimonidine tartrate 1% in petrolatum.^20,21 Clinicians should be attuned to ACD to topical brimonidine in patients previously treated for glaucoma, as prior use of ophthalmic preparations may result in sensitization.^18,20

Antimicrobials

Clindamycin—Clindamycin targets bacterial protein synthesis and is an effective adjunct in the treatment of acne. Despite its widespread and often long-term use, topical clindamycin is a weak sensitizer.²² To date, limited case reports on ACD to topical clindamycin exist.^23-28 Rare clinical patterns of ACD to clindamycin include mimickers of irritant retinoid dermatitis, erythema multiforme, or pustular rosacea.^25,26,29

Metronidazole—Metronidazole is a bactericidal agent that disrupts nucleic acid synthesis with additional anti-inflammatory properties used in the treatment of rosacea. Allergic contact dermatitis to topical metronidazole has been reported.^30-34 In 2006, Beutner at al³⁵ patch tested 215 patients using metronidazole gel 1%, which revealed no positive reactions to indicate contact sensitization. Similarly, Jappe et al³⁶ found no positive reactions to metronidazole 2% in petrolatum in their prospective analysis of 78 rosacea patients, further highlighting the exceptionally low incidence of ACD. Cross-reaction with isothiazolinone, which shares structurally similar properties to metronidazole, has been speculated.^31,34 One patient developed an acute reaction to metronidazole gel 0.75% within 24 hours of application, suggesting that isothiazolinone may act as a sensitizer, though this relationship has not been proven.³¹

Neomycin—Neomycin blocks bacterial protein synthesis and is available in both prescription and over-the-counter (OTC) formulations. It commonly is used to treat and prevent superficial wound infections as an OTC antibiotic and also has otic, ophthalmologic, gastroenterologic, urologic, and peritoneal formulations. It also can be used in the dental and veterinary fields and is present in some animal feeds and in trace amounts in some vaccines for humans. Neomycin is a common antibiotic contact allergen, and the most recently reported 2017-2018 North American Contact Dermatitis Group data cycle placed it at number 12 with 5.4% positivity.³⁷ Co-reactions with bacitracin can occur, substantially limiting OTC topical antibiotic options for allergic patients. A safe alternative for patients with neomycin (and bacitracin and polymyxin) contact allergy is prescription mupirocin.

Bacitracin—Bacitracin interferes with peptidoglycan and cell-wall synthesis to treat superficial cutaneous infections. Similar to neomycin, it also can be found in OTC antibiotic ointments as well as in antibacterial bandages. There are several case reports of patients with both type IV delayed hypersensitivity (contact dermatitis) and type I anaphylactic reactions to bacitracin^38-40; patch testers should be aware of this rare association. Bacitracin was positive in 5.5% of patch tested patients in the 2017-2018 North American Contact Dermatitis Group data cycle,³⁷ and as with neomycin, bacitracin also is commonly patch tested in most screening patch test series.

Polymyxin—Polymyxin is a polypeptide topical antibiotic that is used to treat superficial wound infections and can be used in combination with neomycin and/or bacitracin. Historically, it is a less common antibiotic allergen; however, it is now frequently included in comprehensive patch test series, as the frequency of positive reactions seems to be increasing, probably due to polysensitization with neomycin and bacitracin.

Nystatin—Nystatin is an antifungal that binds to ergosterol and disrupts the cell wall. Cases exist of ACD to topical nystatin as well as systemic ACD from oral exposure, though both are quite rare. Authors have surmised that the overall low rates of ACD may be due to poor skin absorption of nystatin, which also can confound patch testing.^41,42 For patients with suspected ACD to nystatin, repeat open application testing also can be performed to confirm allergy.

Imidazole Antifungals—Similar to nystatins, imidazole antifungals also work by disrupting the fungal cell wall. Imidazole antifungal preparations that have been reported to cause ACD include clotrimazole, miconazole, econazole, and isoconazole, and although cross-reactivity patterns have been described, they are not always reproducible with patch testing.⁴³ In one reported case, tioconazole found in an antifungal nail lacquer triggered ACD involving not only the fingers and toes but also the trunk.⁴⁴ Erythema multiforme–like reactions also have been described from topical use.⁴⁵ Commercial patch test preparations of the most common imidazole allergens do exist. Nonimidazole antifungals remain a safe option for allergic patients.

Antihistamines

Antihistamines, or H1-receptor antagonists, are marketed to be applied topically for relief of pruritus associated with allergic cutaneous reactions. Ironically, they are known to be potent sensitizers themselves. There are 6 main chemical classes of antihistamines: phenothiazines, ethylenediamines, ethanolamines, alkylamines, piperazines, and piperidines. Goossens and Linsen⁴⁶ patch tested 12,460 patients from 1978 to 1997 and found the most positive reactions to promethazine (phenothiazine)(n=12), followed by diphenhydramine (ethanolamine)(n=8) and clemizole (benzimidazole)(n=6). The authors also noted cross-reactions between diphenhydramine derivatives and between promethazine and chlorpromazine.⁴⁶

Doxepin is a tricyclic antidepressant with antihistamine activity and is a well-documented sensitizer.^47-52 Taylor et al⁴⁷ evaluated 97 patients with chronic dermatoses, and patch testing revealed 17 (17.5%) positive reactions to doxepin cream, 13 (76.5%) of which were positive reactions to both the commercial cream and the active ingredient. Patch testing using doxepin dilution as low as 0.5% in petrolatum is sufficient to provoke a strong (++) allergic reaction.^50,51 Early-onset ACD following the use of doxepin cream suggests the possibility of prior sensitization, perhaps with a structurally similar phenothiazine drug.⁵¹ A keen suspicion for ACD in patients using doxepin cream for longer than the recommended duration can help make the diagnosis.^49,52

Topical Analgesics

Nonsteroidal Anti-inflammatory Drugs—Ketoprofen is one of the most frequent culprits of photoallergic contact dermatitis. Pruritic, papulovesicular, and bullous lesions typically develop acutely weeks after exposure. Prolonged photosensitivity is common and can last years after discontinuation of the nonsteroidal anti-inflammatory drug.⁵³ Cases of cross-reactions and co-sensitization to structurally similar substances have been reported, including to benzophenone-related chemicals in sunscreen and aldehyde groups in fragrance mix.^53,54

Diclofenac gel generally is well tolerated in the topical treatment of joint pain and inflammation. In the setting of ACD, patients typically present with dermatitis localized to the area of application.⁵⁵ Immediate cessation and avoidance of topical diclofenac are crucial components of management. Although systemic contact dermatitis has been reported with oral diclofenac use,⁵⁶ a recent report suggested that oral diclofenac may be well tolerated for some patients with topical ACD.⁵⁷

Publications on bufexamac-induced ACD mainly consist of international reports, as this medication has been discontinued in the United States. Bufexamac is a highly sensitizing agent that can lead to severe polymorphic eruptions requiring treatment with prednisolone and even hospitalization.⁵⁸ In one Australian case report, a mother developed an edematous, erythematous, papulovesicular eruption on the breast while breastfeeding her baby, who was being treated with bufexamac cream 5% for infantile eczema.⁵⁹ Carprofen-induced photoallergic contact dermatitis is associated with occupational exposure in pharmaceutical workers.^60,61 A few case reports on other nonsteroidal anti-inflammatory drugs, including etofenamate and aceclofenac, have been published.^62,63

Compounded Medications—Compounded topical analgesics, which help to control pain via multiple combined effects, have gained increasing popularity in the management of chronic neuropathic pain disorders. Only a few recent retrospective studies assessing the efficacy and safety of these medications have mentioned suspected allergic cutaneous reactions.^62,63 In 2015, Turrentine et al⁶⁴ reported a case of ACD to cyclobenzaprine in a compound containing ketamine 10%, diclofenac 5%, baclofen 2%, bupivacaine 1%, cyclobenzaprine 2%, gabapentin 6%, ibuprofen 3%, and pentoxifylline 3% in a proprietary cream base. When patients present with suspected ACD to a compounded pain medication, obtaining individual components for patch testing is key to determining the allergic ingredient(s). We suspect that we will see a rise in reports of ACD as these topical compounds become readily adopted in clinical practices.

Patch Testing for Diagnosis

When patients present with symptoms concerning for ACD to medicaments, the astute clinician should promptly stop the suspected topical medication and consider patch testing. For common allergens such as neomycin, bacitracin, or ethylenediamine, commercial patch test preparations exist and should be used; however, for drugs that do not have a commercial patch test preparation, the patient’s product can be applied as is, keeping in mind that certain preparations (such as retinoids) can cause irritant patch test reactions, which may confound the reading. Alternatively, individual ingredients in the medication’s formulation can be requested from the manufacturer or a compounding pharmacy for targeted testing. Suggested concentrations for patch testing based on the literature and expert reference are listed in the Table. The authors (M.R., A.R.A.) frequently rely on an expert reference⁶⁶ to determine ideal concentrations for patch testing. Referral to a specialized patch test clinic may be appropriate.

Final Interpretation

Although their intent is to heal, topical medicaments also can be a source of ACD. The astute clinician should consider ACD when topicals either no longer seem to help the patient or trigger new-onset dermatitis. Patch testing directly with the culprit medicament, or individual medication ingredients when needed, can lead to the diagnosis, though caution is advised. Stay tuned for part 2 of this series in which we will discuss ACD to topical steroids, immunomodulators, and anesthetic medications.

Topical medications frequently are prescribed in dermatology and provide the advantages of direct skin penetration and targeted application while typically sparing patients from systemic effects. Adverse cutaneous effects include allergic contact dermatitis (ACD), irritant contact dermatitis (ICD), photosensitivity, urticaria, hyperpigmentation or hypopigmentation, atrophy, periorificial dermatitis, and acneform eruptions. Allergic contact dermatitis can develop from the active drug or vehicle components.

Patients with medicament ACD often present with symptoms of pruritus and dermatitis at the site of topical application. They may express concern that the medication is no longer working or seems to be making things worse. Certain sites are more prone to developing medicament dermatitis, including the face, groin, and lower legs. Older adults may be more at risk. Other risk factors include pre-existing skin diseases such as stasis dermatitis, acne, psoriasis, atopic dermatitis, and genital dermatoses.¹ A review of 14,911 patch-tested patients from a single referral clinic revealed that 17.4% had iatrogenic contact dermatitis, with the most common culprits being topical antibiotics, antiseptics, and steroids.²

In this 2-part series, we will focus on the active drug as a source of ACD. Part 1 explores ACD associated with acne and rosacea medications, antimicrobials, antihistamines, and topical pain preparations.

Acne and Rosacea Medications

Retinoids—Topical retinoids are first-line acne treatments that help normalize skin keratinization. Irritant contact dermatitis from retinoids is a well-known and common side effect. Although far less common than ICD, ACD from topical retinoid use has been reported.^3,4 Reactions to tretinoin are most frequently reported in the literature compared to adapalene gel⁵ and tazarotene foam, which have lower potential for sensitization.⁶ Allergic contact dermatitis also has been reported from retinyl palmitate^7,8 in cosmetic creams and from occupational exposure in settings of industrial vitamin A production.⁹ Both ICD and ACD from topical retinoids can present with pruritus, erythema, and scaling. Given this clinical overlap between ACD and ICD, patch testing is crucial in differentiating the underlying etiology of the dermatitis.

Benzoyl Peroxide—Benzoyl peroxide (BP) is another popular topical acne treatment that targets Cutibacterium acnes, a bacterium often implicated in the pathogenesis of acne vulgaris. Similar to retinoids, ICD is more common than ACD. Several cases of ACD to BP have been reported.^10-14 Occasionally, honey-colored crusting associated with ACD to BP can mimic impetigo.¹⁰ Aside from use of BP as an acne treatment, other potential exposures to BP include bleached flour¹³ and orthopedic bone cement. Occupations at risk for potential BP exposure include dental technicians¹⁵ and those working in plastic manufacturing.

Brimonidine—Brimonidine tartrate is a selective α₂-adrenergic agonist initially used to treat open-angle glaucoma and also is used as a topical treatment for rosacea. Allergic reactions to brimonidine eye drops may present with periorbital hyperpigmentation and pruritic bullous lesions.¹⁶ Case reports of topical brimonidine ACD have demonstrated mixed patch test results, with positive patch tests to Mirvaso (Galderma) as is but negative patch tests to pure brimonidine tartrate 0.33%.^17,18 Ringuet and Houle¹⁹ reported the first known positive patch test reaction to pure topical brimonidine, testing with brimonidine tartrate 1% in petrolatum.^20,21 Clinicians should be attuned to ACD to topical brimonidine in patients previously treated for glaucoma, as prior use of ophthalmic preparations may result in sensitization.^18,20

Antimicrobials

Clindamycin—Clindamycin targets bacterial protein synthesis and is an effective adjunct in the treatment of acne. Despite its widespread and often long-term use, topical clindamycin is a weak sensitizer.²² To date, limited case reports on ACD to topical clindamycin exist.^23-28 Rare clinical patterns of ACD to clindamycin include mimickers of irritant retinoid dermatitis, erythema multiforme, or pustular rosacea.^25,26,29

Metronidazole—Metronidazole is a bactericidal agent that disrupts nucleic acid synthesis with additional anti-inflammatory properties used in the treatment of rosacea. Allergic contact dermatitis to topical metronidazole has been reported.^30-34 In 2006, Beutner at al³⁵ patch tested 215 patients using metronidazole gel 1%, which revealed no positive reactions to indicate contact sensitization. Similarly, Jappe et al³⁶ found no positive reactions to metronidazole 2% in petrolatum in their prospective analysis of 78 rosacea patients, further highlighting the exceptionally low incidence of ACD. Cross-reaction with isothiazolinone, which shares structurally similar properties to metronidazole, has been speculated.^31,34 One patient developed an acute reaction to metronidazole gel 0.75% within 24 hours of application, suggesting that isothiazolinone may act as a sensitizer, though this relationship has not been proven.³¹

Neomycin—Neomycin blocks bacterial protein synthesis and is available in both prescription and over-the-counter (OTC) formulations. It commonly is used to treat and prevent superficial wound infections as an OTC antibiotic and also has otic, ophthalmologic, gastroenterologic, urologic, and peritoneal formulations. It also can be used in the dental and veterinary fields and is present in some animal feeds and in trace amounts in some vaccines for humans. Neomycin is a common antibiotic contact allergen, and the most recently reported 2017-2018 North American Contact Dermatitis Group data cycle placed it at number 12 with 5.4% positivity.³⁷ Co-reactions with bacitracin can occur, substantially limiting OTC topical antibiotic options for allergic patients. A safe alternative for patients with neomycin (and bacitracin and polymyxin) contact allergy is prescription mupirocin.

Bacitracin—Bacitracin interferes with peptidoglycan and cell-wall synthesis to treat superficial cutaneous infections. Similar to neomycin, it also can be found in OTC antibiotic ointments as well as in antibacterial bandages. There are several case reports of patients with both type IV delayed hypersensitivity (contact dermatitis) and type I anaphylactic reactions to bacitracin^38-40; patch testers should be aware of this rare association. Bacitracin was positive in 5.5% of patch tested patients in the 2017-2018 North American Contact Dermatitis Group data cycle,³⁷ and as with neomycin, bacitracin also is commonly patch tested in most screening patch test series.

Polymyxin—Polymyxin is a polypeptide topical antibiotic that is used to treat superficial wound infections and can be used in combination with neomycin and/or bacitracin. Historically, it is a less common antibiotic allergen; however, it is now frequently included in comprehensive patch test series, as the frequency of positive reactions seems to be increasing, probably due to polysensitization with neomycin and bacitracin.

Nystatin—Nystatin is an antifungal that binds to ergosterol and disrupts the cell wall. Cases exist of ACD to topical nystatin as well as systemic ACD from oral exposure, though both are quite rare. Authors have surmised that the overall low rates of ACD may be due to poor skin absorption of nystatin, which also can confound patch testing.^41,42 For patients with suspected ACD to nystatin, repeat open application testing also can be performed to confirm allergy.

Imidazole Antifungals—Similar to nystatins, imidazole antifungals also work by disrupting the fungal cell wall. Imidazole antifungal preparations that have been reported to cause ACD include clotrimazole, miconazole, econazole, and isoconazole, and although cross-reactivity patterns have been described, they are not always reproducible with patch testing.⁴³ In one reported case, tioconazole found in an antifungal nail lacquer triggered ACD involving not only the fingers and toes but also the trunk.⁴⁴ Erythema multiforme–like reactions also have been described from topical use.⁴⁵ Commercial patch test preparations of the most common imidazole allergens do exist. Nonimidazole antifungals remain a safe option for allergic patients.

Antihistamines

Antihistamines, or H1-receptor antagonists, are marketed to be applied topically for relief of pruritus associated with allergic cutaneous reactions. Ironically, they are known to be potent sensitizers themselves. There are 6 main chemical classes of antihistamines: phenothiazines, ethylenediamines, ethanolamines, alkylamines, piperazines, and piperidines. Goossens and Linsen⁴⁶ patch tested 12,460 patients from 1978 to 1997 and found the most positive reactions to promethazine (phenothiazine)(n=12), followed by diphenhydramine (ethanolamine)(n=8) and clemizole (benzimidazole)(n=6). The authors also noted cross-reactions between diphenhydramine derivatives and between promethazine and chlorpromazine.⁴⁶

Doxepin is a tricyclic antidepressant with antihistamine activity and is a well-documented sensitizer.^47-52 Taylor et al⁴⁷ evaluated 97 patients with chronic dermatoses, and patch testing revealed 17 (17.5%) positive reactions to doxepin cream, 13 (76.5%) of which were positive reactions to both the commercial cream and the active ingredient. Patch testing using doxepin dilution as low as 0.5% in petrolatum is sufficient to provoke a strong (++) allergic reaction.^50,51 Early-onset ACD following the use of doxepin cream suggests the possibility of prior sensitization, perhaps with a structurally similar phenothiazine drug.⁵¹ A keen suspicion for ACD in patients using doxepin cream for longer than the recommended duration can help make the diagnosis.^49,52

Topical Analgesics

Nonsteroidal Anti-inflammatory Drugs—Ketoprofen is one of the most frequent culprits of photoallergic contact dermatitis. Pruritic, papulovesicular, and bullous lesions typically develop acutely weeks after exposure. Prolonged photosensitivity is common and can last years after discontinuation of the nonsteroidal anti-inflammatory drug.⁵³ Cases of cross-reactions and co-sensitization to structurally similar substances have been reported, including to benzophenone-related chemicals in sunscreen and aldehyde groups in fragrance mix.^53,54

Diclofenac gel generally is well tolerated in the topical treatment of joint pain and inflammation. In the setting of ACD, patients typically present with dermatitis localized to the area of application.⁵⁵ Immediate cessation and avoidance of topical diclofenac are crucial components of management. Although systemic contact dermatitis has been reported with oral diclofenac use,⁵⁶ a recent report suggested that oral diclofenac may be well tolerated for some patients with topical ACD.⁵⁷

Publications on bufexamac-induced ACD mainly consist of international reports, as this medication has been discontinued in the United States. Bufexamac is a highly sensitizing agent that can lead to severe polymorphic eruptions requiring treatment with prednisolone and even hospitalization.⁵⁸ In one Australian case report, a mother developed an edematous, erythematous, papulovesicular eruption on the breast while breastfeeding her baby, who was being treated with bufexamac cream 5% for infantile eczema.⁵⁹ Carprofen-induced photoallergic contact dermatitis is associated with occupational exposure in pharmaceutical workers.^60,61 A few case reports on other nonsteroidal anti-inflammatory drugs, including etofenamate and aceclofenac, have been published.^62,63

Compounded Medications—Compounded topical analgesics, which help to control pain via multiple combined effects, have gained increasing popularity in the management of chronic neuropathic pain disorders. Only a few recent retrospective studies assessing the efficacy and safety of these medications have mentioned suspected allergic cutaneous reactions.^62,63 In 2015, Turrentine et al⁶⁴ reported a case of ACD to cyclobenzaprine in a compound containing ketamine 10%, diclofenac 5%, baclofen 2%, bupivacaine 1%, cyclobenzaprine 2%, gabapentin 6%, ibuprofen 3%, and pentoxifylline 3% in a proprietary cream base. When patients present with suspected ACD to a compounded pain medication, obtaining individual components for patch testing is key to determining the allergic ingredient(s). We suspect that we will see a rise in reports of ACD as these topical compounds become readily adopted in clinical practices.

Patch Testing for Diagnosis

When patients present with symptoms concerning for ACD to medicaments, the astute clinician should promptly stop the suspected topical medication and consider patch testing. For common allergens such as neomycin, bacitracin, or ethylenediamine, commercial patch test preparations exist and should be used; however, for drugs that do not have a commercial patch test preparation, the patient’s product can be applied as is, keeping in mind that certain preparations (such as retinoids) can cause irritant patch test reactions, which may confound the reading. Alternatively, individual ingredients in the medication’s formulation can be requested from the manufacturer or a compounding pharmacy for targeted testing. Suggested concentrations for patch testing based on the literature and expert reference are listed in the Table. The authors (M.R., A.R.A.) frequently rely on an expert reference⁶⁶ to determine ideal concentrations for patch testing. Referral to a specialized patch test clinic may be appropriate.

Final Interpretation

Although their intent is to heal, topical medicaments also can be a source of ACD. The astute clinician should consider ACD when topicals either no longer seem to help the patient or trigger new-onset dermatitis. Patch testing directly with the culprit medicament, or individual medication ingredients when needed, can lead to the diagnosis, though caution is advised. Stay tuned for part 2 of this series in which we will discuss ACD to topical steroids, immunomodulators, and anesthetic medications.

Topical medications frequently are prescribed in dermatology and provide the advantages of direct skin penetration and targeted application while typically sparing patients from systemic effects. Adverse cutaneous effects include allergic contact dermatitis (ACD), irritant contact dermatitis (ICD), photosensitivity, urticaria, hyperpigmentation or hypopigmentation, atrophy, periorificial dermatitis, and acneform eruptions. Allergic contact dermatitis can develop from the active drug or vehicle components.

Patients with medicament ACD often present with symptoms of pruritus and dermatitis at the site of topical application. They may express concern that the medication is no longer working or seems to be making things worse. Certain sites are more prone to developing medicament dermatitis, including the face, groin, and lower legs. Older adults may be more at risk. Other risk factors include pre-existing skin diseases such as stasis dermatitis, acne, psoriasis, atopic dermatitis, and genital dermatoses.¹ A review of 14,911 patch-tested patients from a single referral clinic revealed that 17.4% had iatrogenic contact dermatitis, with the most common culprits being topical antibiotics, antiseptics, and steroids.²

In this 2-part series, we will focus on the active drug as a source of ACD. Part 1 explores ACD associated with acne and rosacea medications, antimicrobials, antihistamines, and topical pain preparations.

Acne and Rosacea Medications

Retinoids—Topical retinoids are first-line acne treatments that help normalize skin keratinization. Irritant contact dermatitis from retinoids is a well-known and common side effect. Although far less common than ICD, ACD from topical retinoid use has been reported.^3,4 Reactions to tretinoin are most frequently reported in the literature compared to adapalene gel⁵ and tazarotene foam, which have lower potential for sensitization.⁶ Allergic contact dermatitis also has been reported from retinyl palmitate^7,8 in cosmetic creams and from occupational exposure in settings of industrial vitamin A production.⁹ Both ICD and ACD from topical retinoids can present with pruritus, erythema, and scaling. Given this clinical overlap between ACD and ICD, patch testing is crucial in differentiating the underlying etiology of the dermatitis.

Benzoyl Peroxide—Benzoyl peroxide (BP) is another popular topical acne treatment that targets Cutibacterium acnes, a bacterium often implicated in the pathogenesis of acne vulgaris. Similar to retinoids, ICD is more common than ACD. Several cases of ACD to BP have been reported.^10-14 Occasionally, honey-colored crusting associated with ACD to BP can mimic impetigo.¹⁰ Aside from use of BP as an acne treatment, other potential exposures to BP include bleached flour¹³ and orthopedic bone cement. Occupations at risk for potential BP exposure include dental technicians¹⁵ and those working in plastic manufacturing.

Brimonidine—Brimonidine tartrate is a selective α₂-adrenergic agonist initially used to treat open-angle glaucoma and also is used as a topical treatment for rosacea. Allergic reactions to brimonidine eye drops may present with periorbital hyperpigmentation and pruritic bullous lesions.¹⁶ Case reports of topical brimonidine ACD have demonstrated mixed patch test results, with positive patch tests to Mirvaso (Galderma) as is but negative patch tests to pure brimonidine tartrate 0.33%.^17,18 Ringuet and Houle¹⁹ reported the first known positive patch test reaction to pure topical brimonidine, testing with brimonidine tartrate 1% in petrolatum.^20,21 Clinicians should be attuned to ACD to topical brimonidine in patients previously treated for glaucoma, as prior use of ophthalmic preparations may result in sensitization.^18,20

Antimicrobials

Clindamycin—Clindamycin targets bacterial protein synthesis and is an effective adjunct in the treatment of acne. Despite its widespread and often long-term use, topical clindamycin is a weak sensitizer.²² To date, limited case reports on ACD to topical clindamycin exist.^23-28 Rare clinical patterns of ACD to clindamycin include mimickers of irritant retinoid dermatitis, erythema multiforme, or pustular rosacea.^25,26,29

Metronidazole—Metronidazole is a bactericidal agent that disrupts nucleic acid synthesis with additional anti-inflammatory properties used in the treatment of rosacea. Allergic contact dermatitis to topical metronidazole has been reported.^30-34 In 2006, Beutner at al³⁵ patch tested 215 patients using metronidazole gel 1%, which revealed no positive reactions to indicate contact sensitization. Similarly, Jappe et al³⁶ found no positive reactions to metronidazole 2% in petrolatum in their prospective analysis of 78 rosacea patients, further highlighting the exceptionally low incidence of ACD. Cross-reaction with isothiazolinone, which shares structurally similar properties to metronidazole, has been speculated.^31,34 One patient developed an acute reaction to metronidazole gel 0.75% within 24 hours of application, suggesting that isothiazolinone may act as a sensitizer, though this relationship has not been proven.³¹

Neomycin—Neomycin blocks bacterial protein synthesis and is available in both prescription and over-the-counter (OTC) formulations. It commonly is used to treat and prevent superficial wound infections as an OTC antibiotic and also has otic, ophthalmologic, gastroenterologic, urologic, and peritoneal formulations. It also can be used in the dental and veterinary fields and is present in some animal feeds and in trace amounts in some vaccines for humans. Neomycin is a common antibiotic contact allergen, and the most recently reported 2017-2018 North American Contact Dermatitis Group data cycle placed it at number 12 with 5.4% positivity.³⁷ Co-reactions with bacitracin can occur, substantially limiting OTC topical antibiotic options for allergic patients. A safe alternative for patients with neomycin (and bacitracin and polymyxin) contact allergy is prescription mupirocin.

Bacitracin—Bacitracin interferes with peptidoglycan and cell-wall synthesis to treat superficial cutaneous infections. Similar to neomycin, it also can be found in OTC antibiotic ointments as well as in antibacterial bandages. There are several case reports of patients with both type IV delayed hypersensitivity (contact dermatitis) and type I anaphylactic reactions to bacitracin^38-40; patch testers should be aware of this rare association. Bacitracin was positive in 5.5% of patch tested patients in the 2017-2018 North American Contact Dermatitis Group data cycle,³⁷ and as with neomycin, bacitracin also is commonly patch tested in most screening patch test series.

Polymyxin—Polymyxin is a polypeptide topical antibiotic that is used to treat superficial wound infections and can be used in combination with neomycin and/or bacitracin. Historically, it is a less common antibiotic allergen; however, it is now frequently included in comprehensive patch test series, as the frequency of positive reactions seems to be increasing, probably due to polysensitization with neomycin and bacitracin.

Nystatin—Nystatin is an antifungal that binds to ergosterol and disrupts the cell wall. Cases exist of ACD to topical nystatin as well as systemic ACD from oral exposure, though both are quite rare. Authors have surmised that the overall low rates of ACD may be due to poor skin absorption of nystatin, which also can confound patch testing.^41,42 For patients with suspected ACD to nystatin, repeat open application testing also can be performed to confirm allergy.

Imidazole Antifungals—Similar to nystatins, imidazole antifungals also work by disrupting the fungal cell wall. Imidazole antifungal preparations that have been reported to cause ACD include clotrimazole, miconazole, econazole, and isoconazole, and although cross-reactivity patterns have been described, they are not always reproducible with patch testing.⁴³ In one reported case, tioconazole found in an antifungal nail lacquer triggered ACD involving not only the fingers and toes but also the trunk.⁴⁴ Erythema multiforme–like reactions also have been described from topical use.⁴⁵ Commercial patch test preparations of the most common imidazole allergens do exist. Nonimidazole antifungals remain a safe option for allergic patients.

Antihistamines

Antihistamines, or H1-receptor antagonists, are marketed to be applied topically for relief of pruritus associated with allergic cutaneous reactions. Ironically, they are known to be potent sensitizers themselves. There are 6 main chemical classes of antihistamines: phenothiazines, ethylenediamines, ethanolamines, alkylamines, piperazines, and piperidines. Goossens and Linsen⁴⁶ patch tested 12,460 patients from 1978 to 1997 and found the most positive reactions to promethazine (phenothiazine)(n=12), followed by diphenhydramine (ethanolamine)(n=8) and clemizole (benzimidazole)(n=6). The authors also noted cross-reactions between diphenhydramine derivatives and between promethazine and chlorpromazine.⁴⁶

Doxepin is a tricyclic antidepressant with antihistamine activity and is a well-documented sensitizer.^47-52 Taylor et al⁴⁷ evaluated 97 patients with chronic dermatoses, and patch testing revealed 17 (17.5%) positive reactions to doxepin cream, 13 (76.5%) of which were positive reactions to both the commercial cream and the active ingredient. Patch testing using doxepin dilution as low as 0.5% in petrolatum is sufficient to provoke a strong (++) allergic reaction.^50,51 Early-onset ACD following the use of doxepin cream suggests the possibility of prior sensitization, perhaps with a structurally similar phenothiazine drug.⁵¹ A keen suspicion for ACD in patients using doxepin cream for longer than the recommended duration can help make the diagnosis.^49,52

Topical Analgesics

Nonsteroidal Anti-inflammatory Drugs—Ketoprofen is one of the most frequent culprits of photoallergic contact dermatitis. Pruritic, papulovesicular, and bullous lesions typically develop acutely weeks after exposure. Prolonged photosensitivity is common and can last years after discontinuation of the nonsteroidal anti-inflammatory drug.⁵³ Cases of cross-reactions and co-sensitization to structurally similar substances have been reported, including to benzophenone-related chemicals in sunscreen and aldehyde groups in fragrance mix.^53,54

Diclofenac gel generally is well tolerated in the topical treatment of joint pain and inflammation. In the setting of ACD, patients typically present with dermatitis localized to the area of application.⁵⁵ Immediate cessation and avoidance of topical diclofenac are crucial components of management. Although systemic contact dermatitis has been reported with oral diclofenac use,⁵⁶ a recent report suggested that oral diclofenac may be well tolerated for some patients with topical ACD.⁵⁷

Publications on bufexamac-induced ACD mainly consist of international reports, as this medication has been discontinued in the United States. Bufexamac is a highly sensitizing agent that can lead to severe polymorphic eruptions requiring treatment with prednisolone and even hospitalization.⁵⁸ In one Australian case report, a mother developed an edematous, erythematous, papulovesicular eruption on the breast while breastfeeding her baby, who was being treated with bufexamac cream 5% for infantile eczema.⁵⁹ Carprofen-induced photoallergic contact dermatitis is associated with occupational exposure in pharmaceutical workers.^60,61 A few case reports on other nonsteroidal anti-inflammatory drugs, including etofenamate and aceclofenac, have been published.^62,63

Compounded Medications—Compounded topical analgesics, which help to control pain via multiple combined effects, have gained increasing popularity in the management of chronic neuropathic pain disorders. Only a few recent retrospective studies assessing the efficacy and safety of these medications have mentioned suspected allergic cutaneous reactions.^62,63 In 2015, Turrentine et al⁶⁴ reported a case of ACD to cyclobenzaprine in a compound containing ketamine 10%, diclofenac 5%, baclofen 2%, bupivacaine 1%, cyclobenzaprine 2%, gabapentin 6%, ibuprofen 3%, and pentoxifylline 3% in a proprietary cream base. When patients present with suspected ACD to a compounded pain medication, obtaining individual components for patch testing is key to determining the allergic ingredient(s). We suspect that we will see a rise in reports of ACD as these topical compounds become readily adopted in clinical practices.

Patch Testing for Diagnosis

When patients present with symptoms concerning for ACD to medicaments, the astute clinician should promptly stop the suspected topical medication and consider patch testing. For common allergens such as neomycin, bacitracin, or ethylenediamine, commercial patch test preparations exist and should be used; however, for drugs that do not have a commercial patch test preparation, the patient’s product can be applied as is, keeping in mind that certain preparations (such as retinoids) can cause irritant patch test reactions, which may confound the reading. Alternatively, individual ingredients in the medication’s formulation can be requested from the manufacturer or a compounding pharmacy for targeted testing. Suggested concentrations for patch testing based on the literature and expert reference are listed in the Table. The authors (M.R., A.R.A.) frequently rely on an expert reference⁶⁶ to determine ideal concentrations for patch testing. Referral to a specialized patch test clinic may be appropriate.

Final Interpretation

Although their intent is to heal, topical medicaments also can be a source of ACD. The astute clinician should consider ACD when topicals either no longer seem to help the patient or trigger new-onset dermatitis. Patch testing directly with the culprit medicament, or individual medication ingredients when needed, can lead to the diagnosis, though caution is advised. Stay tuned for part 2 of this series in which we will discuss ACD to topical steroids, immunomodulators, and anesthetic medications.

Giant hogweed (Heracleum mantegazzianum) is an invasive flowering weed of the family Apiaceae that typically reaches a height of 13 feet, with thick stems; large green leaves; and umbrella-shaped, flat-topped, radial clusters (umbels) of small individual white flowers¹ (Figure 1). Because of the size and beauty of giant hogweed, it was widely planted in 19th century ornamental gardens in the United Kingdom and has since naturalized and spread throughout central Europe, Canada, and the United States.^1,2 The plant most commonly is found in shady areas near rivers and woodlands.¹

Due to the invasive nature of the giant hogweed, its prevalence continues to grow, its eradication remains difficult, and reports of phytophotodermatitis are increasing in number and distribution. In fact, there has been widespread media coverage of the dangers of giant hogweed in the United Kingdom since 2016¹ and in the United States in 2018 and 2019.^3-6

Transmission

Phytophotodermatitis is a type of nonimmunologic dermatitis caused by UV light reacting with a plant-based photosensitizing agent. In the case of giant hogweed, sap from the plant’s fruits, leaves, and stem contain furocoumarins or psoralens.⁷ Upon activation by UVA radiation, furan rings of these compounds create reactive oxygen species and intercalate with DNA pyrimidine bases, which results in cellular death, damage to successive skin layers, and reduced wound healing at the cellular level.⁸ This effect is intensified with increased percutaneous absorption of furocoumarin, which can result from high temperature, humidity, skin infection, lack of protective clothing, and moist conditions.⁹

The highest concentration of phototoxic compounds is found in giant hogweed from June through August,⁷ which, in combination with people increasing their outdoor activity in the summer, results in a greater prevalence and severity of H mantegazzianum phytophotodermatitis during summer months.

Presentation

Phytophotodermatitis caused by giant hogweed can range from burning and erythema to full-thickness chemical burns that require surgical debridement and skin grafting.⁸ After exposure to the offending agent, a harmful skin reaction can start within 15 minutes. After a latent period of approximately 24 hours, erythema, edema, and bullae can appear and generally peak by 72 hours.¹⁰ In addition to cutaneous injury, inhalation of giant hogweed traces can result in obstructive pulmonary symptoms. Eye contact can result in blindness.⁹

In addition to the rash caused by giant hogweed, a “weed-wacker dermatitis” or “strimmer rash” can be caused by the similar-appearing but smaller common hogweed (Heracleum sphondylium). Common hogweed is highly prevalent in the United States and often is confused with the larger giant hogweed because of tall stems and white, flat-topped flowers.

Management

Following contact with giant hogweed, a person should immediately avoid UV exposure and rinse the area with soap and water. UV radiation must be avoided for at least 48 hours. If erythema occurs, a topical steroid can be applied to the affected area; pain can be alleviated by a nonsteroidal anti-inflammatory drug.⁹

Further treatment might be required if bullous lesions are present. Small blisters can be punctured and drained; however, large blisters, extensive epidermal-dermal separation, and large areas of detached epidermis should simply be cleansed and dressed. An oral steroid also can be used to reduce inflammation in moderate and severe cases. Full-thickness injury might require surgical intervention.⁸

Clinical Case

A 27-year-old male landscaper presented to the emergency department with an increasingly painful blistering rash on the arms and neck of 1 day’s duration. He noticed bright red skin and blisters 18 to 24 hours after trimming what he identified as shoulder-high giant hogweed plants. Neither he nor his coworkers were wearing sunscreen or protective clothing as they cleared the plants for several hours. His coworkers developed similar rashes, but his rash was the most severe, requiring treatment in the emergency department.

Physical examination showed innumerable 2- to 10-mm, tense vesicles and bullae on a background of blanching erythema in a striking photodistribution along the neck (Figure 2) and arms (Figure 3). He had notable edema of both arms and several large 3- to 4-cm bullae on the ventral aspects of the forearms.

The patient was diagnosed with severe phytophotodermatitis secondary to contact with H mantegazzianum and was started on oral prednisone 70 mg daily (1 mg/kg/d), which was decreased by 10 mg every 3 days until the course of treatment was complete. He also was instructed to apply mupirocin ointment to open areas and petroleum jelly to intact skin. Additionally, he was advised to practice strict photoprotection for the near and distant future.

Within several days after treatment began, the phytophotodermatitis dramatically improved, with complete resolution in 1 week. Postinflammatory hyperpigmentation resolved after several weeks.

Giant hogweed (Heracleum mantegazzianum) is an invasive flowering weed of the family Apiaceae that typically reaches a height of 13 feet, with thick stems; large green leaves; and umbrella-shaped, flat-topped, radial clusters (umbels) of small individual white flowers¹ (Figure 1). Because of the size and beauty of giant hogweed, it was widely planted in 19th century ornamental gardens in the United Kingdom and has since naturalized and spread throughout central Europe, Canada, and the United States.^1,2 The plant most commonly is found in shady areas near rivers and woodlands.¹

Due to the invasive nature of the giant hogweed, its prevalence continues to grow, its eradication remains difficult, and reports of phytophotodermatitis are increasing in number and distribution. In fact, there has been widespread media coverage of the dangers of giant hogweed in the United Kingdom since 2016¹ and in the United States in 2018 and 2019.^3-6

Transmission

Phytophotodermatitis is a type of nonimmunologic dermatitis caused by UV light reacting with a plant-based photosensitizing agent. In the case of giant hogweed, sap from the plant’s fruits, leaves, and stem contain furocoumarins or psoralens.⁷ Upon activation by UVA radiation, furan rings of these compounds create reactive oxygen species and intercalate with DNA pyrimidine bases, which results in cellular death, damage to successive skin layers, and reduced wound healing at the cellular level.⁸ This effect is intensified with increased percutaneous absorption of furocoumarin, which can result from high temperature, humidity, skin infection, lack of protective clothing, and moist conditions.⁹

The highest concentration of phototoxic compounds is found in giant hogweed from June through August,⁷ which, in combination with people increasing their outdoor activity in the summer, results in a greater prevalence and severity of H mantegazzianum phytophotodermatitis during summer months.

Presentation

Phytophotodermatitis caused by giant hogweed can range from burning and erythema to full-thickness chemical burns that require surgical debridement and skin grafting.⁸ After exposure to the offending agent, a harmful skin reaction can start within 15 minutes. After a latent period of approximately 24 hours, erythema, edema, and bullae can appear and generally peak by 72 hours.¹⁰ In addition to cutaneous injury, inhalation of giant hogweed traces can result in obstructive pulmonary symptoms. Eye contact can result in blindness.⁹

In addition to the rash caused by giant hogweed, a “weed-wacker dermatitis” or “strimmer rash” can be caused by the similar-appearing but smaller common hogweed (Heracleum sphondylium). Common hogweed is highly prevalent in the United States and often is confused with the larger giant hogweed because of tall stems and white, flat-topped flowers.

Management

Following contact with giant hogweed, a person should immediately avoid UV exposure and rinse the area with soap and water. UV radiation must be avoided for at least 48 hours. If erythema occurs, a topical steroid can be applied to the affected area; pain can be alleviated by a nonsteroidal anti-inflammatory drug.⁹

Further treatment might be required if bullous lesions are present. Small blisters can be punctured and drained; however, large blisters, extensive epidermal-dermal separation, and large areas of detached epidermis should simply be cleansed and dressed. An oral steroid also can be used to reduce inflammation in moderate and severe cases. Full-thickness injury might require surgical intervention.⁸

Clinical Case

A 27-year-old male landscaper presented to the emergency department with an increasingly painful blistering rash on the arms and neck of 1 day’s duration. He noticed bright red skin and blisters 18 to 24 hours after trimming what he identified as shoulder-high giant hogweed plants. Neither he nor his coworkers were wearing sunscreen or protective clothing as they cleared the plants for several hours. His coworkers developed similar rashes, but his rash was the most severe, requiring treatment in the emergency department.

Physical examination showed innumerable 2- to 10-mm, tense vesicles and bullae on a background of blanching erythema in a striking photodistribution along the neck (Figure 2) and arms (Figure 3). He had notable edema of both arms and several large 3- to 4-cm bullae on the ventral aspects of the forearms.

The patient was diagnosed with severe phytophotodermatitis secondary to contact with H mantegazzianum and was started on oral prednisone 70 mg daily (1 mg/kg/d), which was decreased by 10 mg every 3 days until the course of treatment was complete. He also was instructed to apply mupirocin ointment to open areas and petroleum jelly to intact skin. Additionally, he was advised to practice strict photoprotection for the near and distant future.

Within several days after treatment began, the phytophotodermatitis dramatically improved, with complete resolution in 1 week. Postinflammatory hyperpigmentation resolved after several weeks.

Giant hogweed (Heracleum mantegazzianum) is an invasive flowering weed of the family Apiaceae that typically reaches a height of 13 feet, with thick stems; large green leaves; and umbrella-shaped, flat-topped, radial clusters (umbels) of small individual white flowers¹ (Figure 1). Because of the size and beauty of giant hogweed, it was widely planted in 19th century ornamental gardens in the United Kingdom and has since naturalized and spread throughout central Europe, Canada, and the United States.^1,2 The plant most commonly is found in shady areas near rivers and woodlands.¹

Due to the invasive nature of the giant hogweed, its prevalence continues to grow, its eradication remains difficult, and reports of phytophotodermatitis are increasing in number and distribution. In fact, there has been widespread media coverage of the dangers of giant hogweed in the United Kingdom since 2016¹ and in the United States in 2018 and 2019.^3-6

Transmission

Phytophotodermatitis is a type of nonimmunologic dermatitis caused by UV light reacting with a plant-based photosensitizing agent. In the case of giant hogweed, sap from the plant’s fruits, leaves, and stem contain furocoumarins or psoralens.⁷ Upon activation by UVA radiation, furan rings of these compounds create reactive oxygen species and intercalate with DNA pyrimidine bases, which results in cellular death, damage to successive skin layers, and reduced wound healing at the cellular level.⁸ This effect is intensified with increased percutaneous absorption of furocoumarin, which can result from high temperature, humidity, skin infection, lack of protective clothing, and moist conditions.⁹

The highest concentration of phototoxic compounds is found in giant hogweed from June through August,⁷ which, in combination with people increasing their outdoor activity in the summer, results in a greater prevalence and severity of H mantegazzianum phytophotodermatitis during summer months.

Presentation

Phytophotodermatitis caused by giant hogweed can range from burning and erythema to full-thickness chemical burns that require surgical debridement and skin grafting.⁸ After exposure to the offending agent, a harmful skin reaction can start within 15 minutes. After a latent period of approximately 24 hours, erythema, edema, and bullae can appear and generally peak by 72 hours.¹⁰ In addition to cutaneous injury, inhalation of giant hogweed traces can result in obstructive pulmonary symptoms. Eye contact can result in blindness.⁹

In addition to the rash caused by giant hogweed, a “weed-wacker dermatitis” or “strimmer rash” can be caused by the similar-appearing but smaller common hogweed (Heracleum sphondylium). Common hogweed is highly prevalent in the United States and often is confused with the larger giant hogweed because of tall stems and white, flat-topped flowers.

Management

Following contact with giant hogweed, a person should immediately avoid UV exposure and rinse the area with soap and water. UV radiation must be avoided for at least 48 hours. If erythema occurs, a topical steroid can be applied to the affected area; pain can be alleviated by a nonsteroidal anti-inflammatory drug.⁹

Further treatment might be required if bullous lesions are present. Small blisters can be punctured and drained; however, large blisters, extensive epidermal-dermal separation, and large areas of detached epidermis should simply be cleansed and dressed. An oral steroid also can be used to reduce inflammation in moderate and severe cases. Full-thickness injury might require surgical intervention.⁸

Clinical Case

A 27-year-old male landscaper presented to the emergency department with an increasingly painful blistering rash on the arms and neck of 1 day’s duration. He noticed bright red skin and blisters 18 to 24 hours after trimming what he identified as shoulder-high giant hogweed plants. Neither he nor his coworkers were wearing sunscreen or protective clothing as they cleared the plants for several hours. His coworkers developed similar rashes, but his rash was the most severe, requiring treatment in the emergency department.

Physical examination showed innumerable 2- to 10-mm, tense vesicles and bullae on a background of blanching erythema in a striking photodistribution along the neck (Figure 2) and arms (Figure 3). He had notable edema of both arms and several large 3- to 4-cm bullae on the ventral aspects of the forearms.

The patient was diagnosed with severe phytophotodermatitis secondary to contact with H mantegazzianum and was started on oral prednisone 70 mg daily (1 mg/kg/d), which was decreased by 10 mg every 3 days until the course of treatment was complete. He also was instructed to apply mupirocin ointment to open areas and petroleum jelly to intact skin. Additionally, he was advised to practice strict photoprotection for the near and distant future.

Within several days after treatment began, the phytophotodermatitis dramatically improved, with complete resolution in 1 week. Postinflammatory hyperpigmentation resolved after several weeks.

To the Editor:

Pityriasis rubra pilaris (PRP) is a rare inflammatory dermatosis of unknown etiology characterized by erythematosquamous salmon-colored plaques with well-demarcated islands of unaffected skin and hyperkeratotic follicles.¹ In the United States, an incidence of 1 in 3500to 5000 patients presenting to dermatology clinics has been reported.² Pityriasis rubra pilaris has several subtypes and variability in presentation that can make accurate and timely diagnosis challenging.^3-5 Herein, we present a case of PRP with complex diagnostic and therapeutic challenges.

A 22-year-old woman presented with symmetrical, well-demarcated, hyperkeratotic, erythematous plaques with a carnauba wax–like appearance on the palms (Figure 1), soles, elbows, and trunk covering approximately 5% of the body surface area. Two weeks prior to presentation, she experienced an upper respiratory tract infection without any treatment and subsequently developed redness on the palms, which became very hard and scaly. The redness then spread to the elbows, soles, and trunk. She reported itching as well as pain in areas of fissuring. Hand mobility became restricted due to thick scale.

The patient’s medical history was notable for suspected psoriasis 9 years prior, but there were no records or biopsy reports that could be obtained to confirm the diagnosis. She also reported a similar skin condition in her father, which also was diagnosed as psoriasis, but this diagnosis could not be verified.

Although the morphology of the lesions was most consistent with localized PRP, atypical psoriasis, palmoplantar keratoderma (PPK), and erythroderma progressive symmetrica (EPS) also were considered given the personal and family history of suspected psoriasis. A biopsy could not be obtained due to an insurance issue. She was started on clobetasol cream 0.05% and ointment. At 2-week follow-up, her condition remained unchanged. Empiric systemic treatment was discussed, which would potentially work for diagnoses of both PRP and psoriasis. Due to the history of psoriasis and level of discomfort, cyclosporine 300 mg once daily was started to gain rapid control of the disease. Methotrexate also was considered due to its efficacy and economic considerations but was not selected due to patient concerns about the medication.

After 10 weeks of cyclosporine treatment, our patient showed some improvement of the skin with decreased scale and flattening of plaques but not complete resolution. At this point, a biopsy was able to be obtained with prior authorization. A 4-mm punch biopsy of the right flank demonstrated a psoriasiform and papillated epidermis with multifocally capped, compact parakeratosis and minimal lymphocytic infiltrate consistent with PRP. Although EPS also was on the histologic differential, clinical history was more consistent with a diagnosis of PRP. There was some minimal improvement with cyclosporine, but with the diagnosis of PRP confirmed, a systemic retinoid became the treatment of choice. Although acitretin is the preferred treatment for PRP, given that pregnancy would be contraindicated during and for 3 years following acitretin therapy, a trial of isotretinoin 40 mg once daily was started due to its shorter half-life compared to acitretin and was continued for 3 months (Figure 2).^6,7

The diagnosis of PRP often can be challenging given the variety of clinical presentations. This case was an atypical presentation of PRP with several learning points, as our patient’s condition did not fit perfectly into any of the 6 types of PRP. The age of onset was atypical at 22 years old. Pityriasis rubra pilaris typically presents with a bimodal age distribution, appearing either in the first decade or the fifth to sixth decades of life.^3,8 Her clinical presentation was atypical for adult-onset types I and II, which typically present with cephalocaudal progression or ichthyosiform dermatitis, respectively. Her presentation also was atypical for juvenile onset in types III, IV, and V, which tend to present in younger children and with different physical examination findings.^3,8

The morphology of our patient’s lesions also was atypical for PRP, PPK, EPS, and psoriasis. The clinical presentation had features of these entities with erythema, fissuring, xerosis, carnauba wax–like appearance, symmetric scale, and well-demarcated plaques. Although these findings are not mutually exclusive, their combined presentation is atypical. Coupled with the ambiguous family history of similar skin disease in the patient’s father, the discussion of genodermatoses, particularly PPK, further confounded the diagnosis.^4,9 When evaluating for PRP, especially with any family history of skin conditions, genodermatoses should be considered. Furthermore, our patient’s remote and unverifiable history of psoriasis serves as a cautionary reminder that prior diagnoses and medical history always should be reasonably scrutinized. Additionally, a drug-induced PRP eruption also should be considered. Although our patient received no medical treatment for the upper respiratory tract infection prior to the onset of PRP, there have been several reports of drug-induced PRP.^10-12

The therapeutic challenge in this case is one that often is encountered in clinical practice. The health care system often may pose a barrier to diagnosis by inhibiting particular services required for adequate patient care. For our patient, diagnosis was delayed by several weeks due to difficulties obtaining a diagnostic skin biopsy. When faced with challenges from health care infrastructure, creativity with treatment options, such as finding an empiric treatment option (cyclosporine in this case), must be considered.

Systemic retinoids have been found to be efficacious treatment options for PRP, but when dealing with a woman of reproductive age, reproductive preferences must be discussed before identifying an appropriate treatment regimen.^1,13-15 The half-life of acitretin compared to isotretinoin is 2 days vs 22 hours.^6,16 With alcohol consumption, acitretin can be metabolized to etretinate, which has a half-life of 120 days.¹⁷ In our patient, isotretinoin was a more manageable option to allow for greater reproductive freedom upon treatment completion.

To the Editor:

Pityriasis rubra pilaris (PRP) is a rare inflammatory dermatosis of unknown etiology characterized by erythematosquamous salmon-colored plaques with well-demarcated islands of unaffected skin and hyperkeratotic follicles.¹ In the United States, an incidence of 1 in 3500to 5000 patients presenting to dermatology clinics has been reported.² Pityriasis rubra pilaris has several subtypes and variability in presentation that can make accurate and timely diagnosis challenging.^3-5 Herein, we present a case of PRP with complex diagnostic and therapeutic challenges.

A 22-year-old woman presented with symmetrical, well-demarcated, hyperkeratotic, erythematous plaques with a carnauba wax–like appearance on the palms (Figure 1), soles, elbows, and trunk covering approximately 5% of the body surface area. Two weeks prior to presentation, she experienced an upper respiratory tract infection without any treatment and subsequently developed redness on the palms, which became very hard and scaly. The redness then spread to the elbows, soles, and trunk. She reported itching as well as pain in areas of fissuring. Hand mobility became restricted due to thick scale.

The patient’s medical history was notable for suspected psoriasis 9 years prior, but there were no records or biopsy reports that could be obtained to confirm the diagnosis. She also reported a similar skin condition in her father, which also was diagnosed as psoriasis, but this diagnosis could not be verified.

Although the morphology of the lesions was most consistent with localized PRP, atypical psoriasis, palmoplantar keratoderma (PPK), and erythroderma progressive symmetrica (EPS) also were considered given the personal and family history of suspected psoriasis. A biopsy could not be obtained due to an insurance issue. She was started on clobetasol cream 0.05% and ointment. At 2-week follow-up, her condition remained unchanged. Empiric systemic treatment was discussed, which would potentially work for diagnoses of both PRP and psoriasis. Due to the history of psoriasis and level of discomfort, cyclosporine 300 mg once daily was started to gain rapid control of the disease. Methotrexate also was considered due to its efficacy and economic considerations but was not selected due to patient concerns about the medication.

After 10 weeks of cyclosporine treatment, our patient showed some improvement of the skin with decreased scale and flattening of plaques but not complete resolution. At this point, a biopsy was able to be obtained with prior authorization. A 4-mm punch biopsy of the right flank demonstrated a psoriasiform and papillated epidermis with multifocally capped, compact parakeratosis and minimal lymphocytic infiltrate consistent with PRP. Although EPS also was on the histologic differential, clinical history was more consistent with a diagnosis of PRP. There was some minimal improvement with cyclosporine, but with the diagnosis of PRP confirmed, a systemic retinoid became the treatment of choice. Although acitretin is the preferred treatment for PRP, given that pregnancy would be contraindicated during and for 3 years following acitretin therapy, a trial of isotretinoin 40 mg once daily was started due to its shorter half-life compared to acitretin and was continued for 3 months (Figure 2).^6,7

The diagnosis of PRP often can be challenging given the variety of clinical presentations. This case was an atypical presentation of PRP with several learning points, as our patient’s condition did not fit perfectly into any of the 6 types of PRP. The age of onset was atypical at 22 years old. Pityriasis rubra pilaris typically presents with a bimodal age distribution, appearing either in the first decade or the fifth to sixth decades of life.^3,8 Her clinical presentation was atypical for adult-onset types I and II, which typically present with cephalocaudal progression or ichthyosiform dermatitis, respectively. Her presentation also was atypical for juvenile onset in types III, IV, and V, which tend to present in younger children and with different physical examination findings.^3,8

The morphology of our patient’s lesions also was atypical for PRP, PPK, EPS, and psoriasis. The clinical presentation had features of these entities with erythema, fissuring, xerosis, carnauba wax–like appearance, symmetric scale, and well-demarcated plaques. Although these findings are not mutually exclusive, their combined presentation is atypical. Coupled with the ambiguous family history of similar skin disease in the patient’s father, the discussion of genodermatoses, particularly PPK, further confounded the diagnosis.^4,9 When evaluating for PRP, especially with any family history of skin conditions, genodermatoses should be considered. Furthermore, our patient’s remote and unverifiable history of psoriasis serves as a cautionary reminder that prior diagnoses and medical history always should be reasonably scrutinized. Additionally, a drug-induced PRP eruption also should be considered. Although our patient received no medical treatment for the upper respiratory tract infection prior to the onset of PRP, there have been several reports of drug-induced PRP.^10-12

The therapeutic challenge in this case is one that often is encountered in clinical practice. The health care system often may pose a barrier to diagnosis by inhibiting particular services required for adequate patient care. For our patient, diagnosis was delayed by several weeks due to difficulties obtaining a diagnostic skin biopsy. When faced with challenges from health care infrastructure, creativity with treatment options, such as finding an empiric treatment option (cyclosporine in this case), must be considered.

Systemic retinoids have been found to be efficacious treatment options for PRP, but when dealing with a woman of reproductive age, reproductive preferences must be discussed before identifying an appropriate treatment regimen.^1,13-15 The half-life of acitretin compared to isotretinoin is 2 days vs 22 hours.^6,16 With alcohol consumption, acitretin can be metabolized to etretinate, which has a half-life of 120 days.¹⁷ In our patient, isotretinoin was a more manageable option to allow for greater reproductive freedom upon treatment completion.

To the Editor:

Pityriasis rubra pilaris (PRP) is a rare inflammatory dermatosis of unknown etiology characterized by erythematosquamous salmon-colored plaques with well-demarcated islands of unaffected skin and hyperkeratotic follicles.¹ In the United States, an incidence of 1 in 3500to 5000 patients presenting to dermatology clinics has been reported.² Pityriasis rubra pilaris has several subtypes and variability in presentation that can make accurate and timely diagnosis challenging.^3-5 Herein, we present a case of PRP with complex diagnostic and therapeutic challenges.

A 22-year-old woman presented with symmetrical, well-demarcated, hyperkeratotic, erythematous plaques with a carnauba wax–like appearance on the palms (Figure 1), soles, elbows, and trunk covering approximately 5% of the body surface area. Two weeks prior to presentation, she experienced an upper respiratory tract infection without any treatment and subsequently developed redness on the palms, which became very hard and scaly. The redness then spread to the elbows, soles, and trunk. She reported itching as well as pain in areas of fissuring. Hand mobility became restricted due to thick scale.

The patient’s medical history was notable for suspected psoriasis 9 years prior, but there were no records or biopsy reports that could be obtained to confirm the diagnosis. She also reported a similar skin condition in her father, which also was diagnosed as psoriasis, but this diagnosis could not be verified.

Although the morphology of the lesions was most consistent with localized PRP, atypical psoriasis, palmoplantar keratoderma (PPK), and erythroderma progressive symmetrica (EPS) also were considered given the personal and family history of suspected psoriasis. A biopsy could not be obtained due to an insurance issue. She was started on clobetasol cream 0.05% and ointment. At 2-week follow-up, her condition remained unchanged. Empiric systemic treatment was discussed, which would potentially work for diagnoses of both PRP and psoriasis. Due to the history of psoriasis and level of discomfort, cyclosporine 300 mg once daily was started to gain rapid control of the disease. Methotrexate also was considered due to its efficacy and economic considerations but was not selected due to patient concerns about the medication.

After 10 weeks of cyclosporine treatment, our patient showed some improvement of the skin with decreased scale and flattening of plaques but not complete resolution. At this point, a biopsy was able to be obtained with prior authorization. A 4-mm punch biopsy of the right flank demonstrated a psoriasiform and papillated epidermis with multifocally capped, compact parakeratosis and minimal lymphocytic infiltrate consistent with PRP. Although EPS also was on the histologic differential, clinical history was more consistent with a diagnosis of PRP. There was some minimal improvement with cyclosporine, but with the diagnosis of PRP confirmed, a systemic retinoid became the treatment of choice. Although acitretin is the preferred treatment for PRP, given that pregnancy would be contraindicated during and for 3 years following acitretin therapy, a trial of isotretinoin 40 mg once daily was started due to its shorter half-life compared to acitretin and was continued for 3 months (Figure 2).^6,7

The diagnosis of PRP often can be challenging given the variety of clinical presentations. This case was an atypical presentation of PRP with several learning points, as our patient’s condition did not fit perfectly into any of the 6 types of PRP. The age of onset was atypical at 22 years old. Pityriasis rubra pilaris typically presents with a bimodal age distribution, appearing either in the first decade or the fifth to sixth decades of life.^3,8 Her clinical presentation was atypical for adult-onset types I and II, which typically present with cephalocaudal progression or ichthyosiform dermatitis, respectively. Her presentation also was atypical for juvenile onset in types III, IV, and V, which tend to present in younger children and with different physical examination findings.^3,8

The morphology of our patient’s lesions also was atypical for PRP, PPK, EPS, and psoriasis. The clinical presentation had features of these entities with erythema, fissuring, xerosis, carnauba wax–like appearance, symmetric scale, and well-demarcated plaques. Although these findings are not mutually exclusive, their combined presentation is atypical. Coupled with the ambiguous family history of similar skin disease in the patient’s father, the discussion of genodermatoses, particularly PPK, further confounded the diagnosis.^4,9 When evaluating for PRP, especially with any family history of skin conditions, genodermatoses should be considered. Furthermore, our patient’s remote and unverifiable history of psoriasis serves as a cautionary reminder that prior diagnoses and medical history always should be reasonably scrutinized. Additionally, a drug-induced PRP eruption also should be considered. Although our patient received no medical treatment for the upper respiratory tract infection prior to the onset of PRP, there have been several reports of drug-induced PRP.^10-12

The therapeutic challenge in this case is one that often is encountered in clinical practice. The health care system often may pose a barrier to diagnosis by inhibiting particular services required for adequate patient care. For our patient, diagnosis was delayed by several weeks due to difficulties obtaining a diagnostic skin biopsy. When faced with challenges from health care infrastructure, creativity with treatment options, such as finding an empiric treatment option (cyclosporine in this case), must be considered.

Systemic retinoids have been found to be efficacious treatment options for PRP, but when dealing with a woman of reproductive age, reproductive preferences must be discussed before identifying an appropriate treatment regimen.^1,13-15 The half-life of acitretin compared to isotretinoin is 2 days vs 22 hours.^6,16 With alcohol consumption, acitretin can be metabolized to etretinate, which has a half-life of 120 days.¹⁷ In our patient, isotretinoin was a more manageable option to allow for greater reproductive freedom upon treatment completion.

With the strong likelihood that dermatologists in the United States will have to resolve dermatologic issues created by cultural cosmetic practices originating elsewhere, strategies for an open nonjudgmental approach are instrumental, according to a dermatologist with expertise in these types of cases who spoke at the Skin of Color Update 2021.

“Instead of avoiding the discussion of cultural practices, we should discuss them and be open about them. It fosters a comfortable environment, trust, and better compliance,” reported Neelam Ajit Vashi, MD, founding director of the Boston University Center for Ethnic Skin.

Out of fear of causing offense, a desire to be discreet, or of personal discomfort with foreign cultural practices, some clinicians might elect to limit themselves to the information that the patient volunteers, which is a mistake, according to Dr. Vashi.

“The avoidance of topics around culture actually limits the ability to have a successful relationship,” she maintained.

Successful encounters are not just based on a willingness to listen, Dr. Vashi said. Clinicians should be seeking a base of knowledge. With growing globalization and widespread immigration, “it is increasingly important for dermatologists in the U.S. to understand the role of cultural practices [in creating skin problems] and recognize the sequelae,” Dr. Vashi said.

Taking some common examples of dermatologic complaints created by cosmetic practices originating elsewhere, Dr. Vashi described key clinical points in addressing complications related to henna, hair removal through threading, and placement of decorative adornments on the forehead, called bindi. In addition, she pointed out common issues with facial and body marking created with kumkum powder, hair oils, and skin lightening agents.
 

Black henna

For cosmetic enhancement, henna is relatively benign. It is also no longer confined to the south Asian communities where it originated. However, Dr. Vashi pointed out that patients of south Asian origin or descent might be more likely to use black henna, a variety with more risks.

Black henna contains additives, such as diaminobenzenes and p-phenylenediamine (PPD), to darken the tone of the product as well as provide other desired characteristics, such as an accelerated drying time. While some patients do develop reactions to conventional henna, the risks of black henna are greater.

“The acute contact dermatitis reactions can include dyspigmentation, leukoderma, and keloids,” Dr. Vashi said. Other complications include erythema multiforme, temporary hypertrichosis, and systemic allergic reactions, such as angioedema.

While those who have had a reaction to henna should avoid further contact, Dr. Vashi warned that sequelae can include cross reactions with latex and rubber as well as some pharmaceutical agents, such as sulfonamides. When taking a patient history, she noted, be aware that risks of henna extend to the hairdressers and cosmeticians who sometimes apply these products on others.

Hair threading, bindi, and kumkum

Hair threading, another practice popularized in south Asia and now growing in popularity globally, involves capturing hairs between cotton threads for removal of both the hair and its follicle. It is a relatively rapid and efficient method of permanent depilation. In addition to pain and erythema, Dr. Vashi reported that the complications associated with hair threading include pigmentary changes, infections such as bullous impetigo, and lesions of koebnerization – such as vitiligo and lichen planus.

Bindi, a Hindi tradition that involves placing adornments between the eyebrows, and kumkum, a powder typically made from turmeric to be employed for decorative markings, have also spread to use outside of their cultural context, according to Dr. Vashi. She said that the complications of these two cosmetic practices are shared, and stem largely from contact dermatitis.

Veena Nair/Moment/Getty Images

Hair oils, skin-lightening agents

Culturally-linked hair oils among patients from south Asia or Africa – or descendants from these areas – can damage hair in a variety of ways as well as cause contact dermatitis. The oils can also exacerbate existing skin diseases.

“Oils with high oleic acid, such as coconut or olive oils or shea butter, can worsen seborrheic dermatitis,” Dr. Vashi cautioned.

Of this list of dermatologic issues induced by culturally linked cosmetic practices, skin lightening agents might pose the most risk for permanent and irreversible complications. Dr. Vashi said that up to 70% of patients using lighteners develop complications, and there is a relationship between the severity of side effects as duration of use increases.

“The problem is that ingredients of many of these products, which are imported illegally and sold on the black market, are often not disclosed,” Dr. Vashi said. Some contain a high content of metals such as lead, copper, and iron, whether they are added intentionally or end up in the product because of poor quality control. For those developing adverse events associated with the products, the obvious treatment is discontinuation.

When patients are unwilling to discontinue any of the products that have led to dermatologic issues, Dr. Vashi encouraged physicians “to take a middle ground.” Simple avoidance can be challenging for practices that are culturally meaningful. In respecting cultural differences, she encouraged tolerance and compromise.

“Often these patients will be doing an alternative medication or intervention, but this does not mean that they are not accepting what we have to offer,” she said. She indicated that mutual respect will lead to better solutions.

The awareness of common cultural practices that can have a harmful impact on the skin is an area of practice that deserves more attention, Andrew F. Alexis, MD, vice-chair for diversity and inclusion in the department of dermatology at Weill Cornell Medical Center, New York, said in an interview.

With the strong likelihood that dermatologists in the United States will have to resolve dermatologic issues created by cultural cosmetic practices originating elsewhere, strategies for an open nonjudgmental approach are instrumental, according to a dermatologist with expertise in these types of cases who spoke at the Skin of Color Update 2021.

“Instead of avoiding the discussion of cultural practices, we should discuss them and be open about them. It fosters a comfortable environment, trust, and better compliance,” reported Neelam Ajit Vashi, MD, founding director of the Boston University Center for Ethnic Skin.

Out of fear of causing offense, a desire to be discreet, or of personal discomfort with foreign cultural practices, some clinicians might elect to limit themselves to the information that the patient volunteers, which is a mistake, according to Dr. Vashi.

“The avoidance of topics around culture actually limits the ability to have a successful relationship,” she maintained.

Successful encounters are not just based on a willingness to listen, Dr. Vashi said. Clinicians should be seeking a base of knowledge. With growing globalization and widespread immigration, “it is increasingly important for dermatologists in the U.S. to understand the role of cultural practices [in creating skin problems] and recognize the sequelae,” Dr. Vashi said.

Taking some common examples of dermatologic complaints created by cosmetic practices originating elsewhere, Dr. Vashi described key clinical points in addressing complications related to henna, hair removal through threading, and placement of decorative adornments on the forehead, called bindi. In addition, she pointed out common issues with facial and body marking created with kumkum powder, hair oils, and skin lightening agents.
 

Black henna

For cosmetic enhancement, henna is relatively benign. It is also no longer confined to the south Asian communities where it originated. However, Dr. Vashi pointed out that patients of south Asian origin or descent might be more likely to use black henna, a variety with more risks.

Black henna contains additives, such as diaminobenzenes and p-phenylenediamine (PPD), to darken the tone of the product as well as provide other desired characteristics, such as an accelerated drying time. While some patients do develop reactions to conventional henna, the risks of black henna are greater.

“The acute contact dermatitis reactions can include dyspigmentation, leukoderma, and keloids,” Dr. Vashi said. Other complications include erythema multiforme, temporary hypertrichosis, and systemic allergic reactions, such as angioedema.

While those who have had a reaction to henna should avoid further contact, Dr. Vashi warned that sequelae can include cross reactions with latex and rubber as well as some pharmaceutical agents, such as sulfonamides. When taking a patient history, she noted, be aware that risks of henna extend to the hairdressers and cosmeticians who sometimes apply these products on others.

Hair threading, bindi, and kumkum

Hair threading, another practice popularized in south Asia and now growing in popularity globally, involves capturing hairs between cotton threads for removal of both the hair and its follicle. It is a relatively rapid and efficient method of permanent depilation. In addition to pain and erythema, Dr. Vashi reported that the complications associated with hair threading include pigmentary changes, infections such as bullous impetigo, and lesions of koebnerization – such as vitiligo and lichen planus.

Bindi, a Hindi tradition that involves placing adornments between the eyebrows, and kumkum, a powder typically made from turmeric to be employed for decorative markings, have also spread to use outside of their cultural context, according to Dr. Vashi. She said that the complications of these two cosmetic practices are shared, and stem largely from contact dermatitis.

Veena Nair/Moment/Getty Images

Hair oils, skin-lightening agents

Culturally-linked hair oils among patients from south Asia or Africa – or descendants from these areas – can damage hair in a variety of ways as well as cause contact dermatitis. The oils can also exacerbate existing skin diseases.

“Oils with high oleic acid, such as coconut or olive oils or shea butter, can worsen seborrheic dermatitis,” Dr. Vashi cautioned.

Of this list of dermatologic issues induced by culturally linked cosmetic practices, skin lightening agents might pose the most risk for permanent and irreversible complications. Dr. Vashi said that up to 70% of patients using lighteners develop complications, and there is a relationship between the severity of side effects as duration of use increases.

“The problem is that ingredients of many of these products, which are imported illegally and sold on the black market, are often not disclosed,” Dr. Vashi said. Some contain a high content of metals such as lead, copper, and iron, whether they are added intentionally or end up in the product because of poor quality control. For those developing adverse events associated with the products, the obvious treatment is discontinuation.

When patients are unwilling to discontinue any of the products that have led to dermatologic issues, Dr. Vashi encouraged physicians “to take a middle ground.” Simple avoidance can be challenging for practices that are culturally meaningful. In respecting cultural differences, she encouraged tolerance and compromise.

“Often these patients will be doing an alternative medication or intervention, but this does not mean that they are not accepting what we have to offer,” she said. She indicated that mutual respect will lead to better solutions.

The awareness of common cultural practices that can have a harmful impact on the skin is an area of practice that deserves more attention, Andrew F. Alexis, MD, vice-chair for diversity and inclusion in the department of dermatology at Weill Cornell Medical Center, New York, said in an interview.

With the strong likelihood that dermatologists in the United States will have to resolve dermatologic issues created by cultural cosmetic practices originating elsewhere, strategies for an open nonjudgmental approach are instrumental, according to a dermatologist with expertise in these types of cases who spoke at the Skin of Color Update 2021.

“Instead of avoiding the discussion of cultural practices, we should discuss them and be open about them. It fosters a comfortable environment, trust, and better compliance,” reported Neelam Ajit Vashi, MD, founding director of the Boston University Center for Ethnic Skin.

Out of fear of causing offense, a desire to be discreet, or of personal discomfort with foreign cultural practices, some clinicians might elect to limit themselves to the information that the patient volunteers, which is a mistake, according to Dr. Vashi.

“The avoidance of topics around culture actually limits the ability to have a successful relationship,” she maintained.

Successful encounters are not just based on a willingness to listen, Dr. Vashi said. Clinicians should be seeking a base of knowledge. With growing globalization and widespread immigration, “it is increasingly important for dermatologists in the U.S. to understand the role of cultural practices [in creating skin problems] and recognize the sequelae,” Dr. Vashi said.

Taking some common examples of dermatologic complaints created by cosmetic practices originating elsewhere, Dr. Vashi described key clinical points in addressing complications related to henna, hair removal through threading, and placement of decorative adornments on the forehead, called bindi. In addition, she pointed out common issues with facial and body marking created with kumkum powder, hair oils, and skin lightening agents.
 

Black henna

For cosmetic enhancement, henna is relatively benign. It is also no longer confined to the south Asian communities where it originated. However, Dr. Vashi pointed out that patients of south Asian origin or descent might be more likely to use black henna, a variety with more risks.

Black henna contains additives, such as diaminobenzenes and p-phenylenediamine (PPD), to darken the tone of the product as well as provide other desired characteristics, such as an accelerated drying time. While some patients do develop reactions to conventional henna, the risks of black henna are greater.

“The acute contact dermatitis reactions can include dyspigmentation, leukoderma, and keloids,” Dr. Vashi said. Other complications include erythema multiforme, temporary hypertrichosis, and systemic allergic reactions, such as angioedema.

While those who have had a reaction to henna should avoid further contact, Dr. Vashi warned that sequelae can include cross reactions with latex and rubber as well as some pharmaceutical agents, such as sulfonamides. When taking a patient history, she noted, be aware that risks of henna extend to the hairdressers and cosmeticians who sometimes apply these products on others.

Hair threading, bindi, and kumkum

Hair threading, another practice popularized in south Asia and now growing in popularity globally, involves capturing hairs between cotton threads for removal of both the hair and its follicle. It is a relatively rapid and efficient method of permanent depilation. In addition to pain and erythema, Dr. Vashi reported that the complications associated with hair threading include pigmentary changes, infections such as bullous impetigo, and lesions of koebnerization – such as vitiligo and lichen planus.

Bindi, a Hindi tradition that involves placing adornments between the eyebrows, and kumkum, a powder typically made from turmeric to be employed for decorative markings, have also spread to use outside of their cultural context, according to Dr. Vashi. She said that the complications of these two cosmetic practices are shared, and stem largely from contact dermatitis.

Veena Nair/Moment/Getty Images

Hair oils, skin-lightening agents

Culturally-linked hair oils among patients from south Asia or Africa – or descendants from these areas – can damage hair in a variety of ways as well as cause contact dermatitis. The oils can also exacerbate existing skin diseases.

“Oils with high oleic acid, such as coconut or olive oils or shea butter, can worsen seborrheic dermatitis,” Dr. Vashi cautioned.

Of this list of dermatologic issues induced by culturally linked cosmetic practices, skin lightening agents might pose the most risk for permanent and irreversible complications. Dr. Vashi said that up to 70% of patients using lighteners develop complications, and there is a relationship between the severity of side effects as duration of use increases.

“The problem is that ingredients of many of these products, which are imported illegally and sold on the black market, are often not disclosed,” Dr. Vashi said. Some contain a high content of metals such as lead, copper, and iron, whether they are added intentionally or end up in the product because of poor quality control. For those developing adverse events associated with the products, the obvious treatment is discontinuation.

When patients are unwilling to discontinue any of the products that have led to dermatologic issues, Dr. Vashi encouraged physicians “to take a middle ground.” Simple avoidance can be challenging for practices that are culturally meaningful. In respecting cultural differences, she encouraged tolerance and compromise.

“Often these patients will be doing an alternative medication or intervention, but this does not mean that they are not accepting what we have to offer,” she said. She indicated that mutual respect will lead to better solutions.

The awareness of common cultural practices that can have a harmful impact on the skin is an area of practice that deserves more attention, Andrew F. Alexis, MD, vice-chair for diversity and inclusion in the department of dermatology at Weill Cornell Medical Center, New York, said in an interview.

Dermatology is an often-underutilized resource in the hospital setting. As the health care landscape has evolved, so has the role of the inpatient dermatologist.^1-3 Structural changes in the health system and advances in therapies have shifted dermatology from an admitting service to an almost exclusively outpatient practice. Improved treatment modalities led to decreases in the number of patients requiring admission for chronic dermatoses, and outpatient clinics began offering therapies once limited to hospitals.^1,4 Inpatient dermatology consultations emerged and continue to have profound effects on hospitalized patients regardless of their reason for admission.^1-11

Inpatient dermatologists supply knowledge in areas primary medical teams lack, and there is evidence that dermatology consultations improve the quality of care while decreasing cost.^2,5-7 Establishing correct diagnoses, preventing exposure to unnecessary medications, and reducing hospitalization duration and readmission rates are a few ways dermatology consultations positively impact hospitalized patients.^2,5-7,9,10 This study highlights the role of the dermatologist in the care of hospitalized patients at a large academic medical center in an urban setting and reveals how consultation supports the efficiency and efficacy of other services.

Materials and Methods

Study Design—This single-institution, cross-sectional retrospective study included all hospitalized patients at the Thomas Jefferson University Hospital (Philadelphia, Pennsylvania), who received an inpatient dermatology consultation completed by physicians of Jefferson Dermatology Associates between January 1, 2019, and December 31, 2019. The institutional review board at Thomas Jefferson University approved this study.

Data Collection—A list of all inpatient dermatology consultations in 2019 was provided by Jefferson Dermatology Associates. Through a retrospective chart review, data regarding the consultations were collected from the electronic medical record (Epic Systems) and recorded into the Research Electronic Data Capture system. Data on patient demographics, the primary medical team, the dermatology evaluation, and the hospital course of the patient were collected.

Results

Patient Characteristics—Dermatology received 253 inpatient consultation requests during this time period; 53% of patients were female and 47% were male, with a mean age of 55 years. Most patients were White (57%), while 34% were Black. Five percent and 4% of patients were Asian and Hispanic or Latino, respectively (Table 1). The mean duration of hospitalization for all patients was 15 days, and the average number of days to discharge following the first encounter with dermatology was 10 days.

Requesting Team and Reason for Consultation—Internal medicine consulted dermatology most frequently (34% of all consultations), followed by emergency medicine (14%) and a variety of other services (Table 1). Most dermatology consultations were placed to assist in achieving a diagnosis of a cutaneous condition (77%), while a minority were to assist in the management of a previously diagnosed disease (22%). A small fraction of consultations (5%) were to complete full-body skin examinations (FBSEs) to rule out infection or malignancy in candidates for organ transplantation, left ventricular assist devices, or certain chemotherapies. One FBSE was conducted to search for a primary tumor in a patient diagnosed with metastatic melanoma.

Most Common Final Diagnoses and Consultation Impact—Table 2 lists the most common final diagnosis categories, as well as the effects of the consultation on diagnosis, management, biopsies, hospitalization, and clinical improvement as documented by the primary medical provider. The most common final diagnoses were inflammatory and autoimmune (39%), such as contact dermatitis and seborrheic dermatitis; infectious (23%), such as varicella (primary or zoster) and bacterial furunculosis; drug reactions (20%), such as morbilliform drug eruptions; vascular (8%), such as vasculitis and calciphylaxis; neoplastic (7%), such as keratinocyte carcinomas and leukemia cutis; and other (15%), such as xerosis, keratosis pilaris, and miliaria rubra.

Impact on Diagnosis—Fifty-six percent of all consultations resulted in a change in diagnosis. When dermatology was consulted specifically to assist in the diagnosis of a patient (195 consultations), the working diagnosis of the primary team was changed 69% of the time. Thirty-five of these consultation requests had no preliminary diagnosis, and the primary team listed the working diagnosis as either rash or a morphologic description of the lesion(s). Sixty-three percent of suspected drug eruptions ended with a diagnosis of a form of drug eruption, while 20% of consultations for suspected cellulitis or bacterial infections were confirmed to be cellulitis or soft tissue infections.

Impact on Management—Regardless of the reason for the consultation, most consultations (86%) resulted in a change in management. The remaining 14% consisted of FBSEs with benign findings; cases of cutaneous metastases and leukemia cutis managed by oncology; as well as select cases of purpura fulminans, postfebrile desquamation, and postinflammatory hyperpigmentation.

Changes in management included alterations in medications, requests for additional laboratory work or imaging, additional consultation requests, biopsies, or specific wound care instructions. Seventy-five percent of all consultations were given specific medication recommendations by dermatology. Most (61%) were recommended to be given a topical steroid, antibiotic, or both. However, 45% of all consultations were recommended to initiate a systemic medication, most commonly antihistamines, antibiotics, steroids, antivirals, or immunomodulators. Dermatology recommended discontinuing specific medications in 16% of all consultations, with antibiotics being the most frequent culprit (17 antibiotics discontinued), owing to drug eruptions or misdiagnosed infections. Vancomycin, piperacillin-tazobactam, and trimethoprim-sulfamethoxazole were the most frequently discontinued antibiotics.

Dermatology was consulted for assistance in management of previously diagnosed cutaneous conditions 56 times (22% of all consultations), often regarding complicated cases of hidradenitis suppurativa (9 cases), pyoderma gangrenosum (5 cases), bullous pemphigoid (4 cases), or erythroderma (4 cases). Most of these cases required a single dermatology encounter to provide recommendations (71%), and 21% required 1 additional follow-up. Sixty-three percent of patients consulted for management assistance were noted to have improvement in their cutaneous condition by time of discharge, as documented by the primary provider in the medical record.

Twenty-eight percent of all consultations required at least 1 biopsy. Seventy-two percent of all biopsies were consistent with the dermatologist’s working diagnosis or highest-ranked differential diagnosis, and 16% of biopsy results were consistent with the second- or third-ranked diagnosis. The primary teams requested a biopsy 38 times to assist in diagnosis, as documented in the progress note or consultation request. Only 21 of these consultations (55% of requests) received at least 1 biopsy, as the remaining consultations did not require a biopsy to establish a diagnosis. The most common final diagnoses of consultations receiving biopsies included drug eruptions (5), leukemia cutis (4), vasculopathies (4), vasculitis (4), and calciphylaxis (3).

Impact on Hospitalization and Efficacy—Dermatology performed 217 consultations regarding patients already admitted to the hospital, and 92% remained hospitalized either due to comorbidities or complicated cutaneous conditions following the consultation. The remaining 8% were cleared for discharge. Dermatology received 36 consultation requests from emergency medicine physicians. Fifty-three percent of these patients were admitted, while the remaining 47% were discharged from the emergency department or its observation unit following evaluation.

Fifty-one percent of all consultations were noted to have improvement in their cutaneous condition by the time of discharge, as noted in the physical examination, progress note, or discharge summary of the primary team. Thirty percent of cases remained stable, where improvement was not noted in in the medical record. Most of these cases involved keratinocyte carcinomas scheduled for outpatient excision, benign melanocytic nevi found on FBSE, and benign etiologies that led to immediate discharge following consultation. Three percent of all consultations were noted to have worsened following consultation, including cases of calciphylaxis, vasculopathies, and purpura fulminans, as well as patients who elected for palliative care and hospice. The cutaneous condition by the time of discharge could not be determined from the medical record in 16% of all consultations.

Eighty-five percent of all consultations required a single encounter with dermatology. An additional 10% required a single follow-up with dermatology, while only 5% of patients required 3 or more encounters. Notably, these cases included patients with 1 or more severe cutaneous diseases, such as Sweet syndrome, calciphylaxis, Stevens-Johnson syndrome/toxic epidermal necrolysis, and hidradenitis suppurativa.

Comment

Although dermatology often is viewed as an outpatient specialty, this study provides a glimpse into the ways inpatient dermatology consultations optimize the care of hospitalized patients. Most consultations involved assistance in diagnosing an unknown condition, but several regarded pre-existing skin disorders requiring management aid. As a variety of medical specialties requested consultations, dermatology was able to provide care to a diverse group of patients with conditions varying in complexity and severity. Several specialties benefited from niche dermatologic expertise: hematology and oncology frequently requested dermatology to assist in diagnosis and management of the toxic effects of chemotherapy, cutaneous metastasis, or suspected cutaneous infections in immunocompromised patients. Cardiology patients were frequently evaluated for potential malignancy or infection prior to heart transplantation and initiation of antirejection immunosuppressants. Dermatology was consulted to differentiate cutaneous manifestations of critical illness from underlying systemic disease in the intensive care unit, and patients presenting to the emergency department often were examined to determine if hospital admission was necessary, with 47% of these consultations resulting in a discharge following evaluation by a dermatologist.

Our results were consistent with prior studies^1,5,6 that have reported frequent changes in final diagnosis following dermatology consultation, with 69% of working diagnoses changed in this study when consultation was requested for diagnostic assistance. When dermatology was consulted for diagnostic assistance, several of these cases lacked a preliminary differential diagnosis. Although the absence of a documented differential diagnosis may not necessarily reflect a lack of suspicion for a particular etiology, 86% of all consultations included a ranked differential or working diagnosis either in the consultation request or progress note prior to consultation. The final diagnoses of consultations without a preliminary diagnosis varied from the mild and localized to systemic and severe, further suggesting these cases reflected knowledge gaps of the primary medical team.

Integration of dermatology into the care of hospitalized patients could provide an opportunity for education of primary medical teams. With frequent consultation, primary medical teams may become more comfortable diagnosing and managing common cutaneous conditions specific to their specialty or extended hospitalizations.

Several consultations were requested to aid in management of cases of hidradenitis suppurativa, pyoderma gangrenosum, or bullous pemphigoid that either failed outpatient therapy or were complicated by superinfections. Despite the ranges in complexity, the majority of all consultations required a single encounter and led to improvement by the time of discharge, demonstrating the efficacy and efficiency of inpatient dermatologists.

Dermatology consultations often led to changes in management involving medications and additional workup. Changes in management also extended to specific wound care instructions provided by dermatology, as expected for cases of Stevens-Johnson syndrome/toxic epidermal necrolysis, Sweet syndrome, hidradenitis suppurativa, and pyoderma gangrenosum. However, patients with the sequelae of extended hospitalizations, such as chronic wounds, pressure ulcers, and edema bullae, also benefited from this expertise.

When patients required a biopsy, the final diagnoses were consistent with the dermatologist’s number one differential diagnosis or top 3 differential diagnoses 72% and 88% of the time, respectively. Only 55% of cases where the primary team requested a biopsy ultimately required a biopsy, as many involved clinical diagnoses such as urticaria. Not only was dermatology accurate in their preliminary diagnoses, but they decreased cost and morbidity by avoiding unnecessary procedures.

This study provided additional evidence to support the integration of dermatology into the hospital setting for the benefit of patients, primary medical teams, and hospital systems. Dermatology offers high-value care through the efficient diagnosis and management of hospitalized patients, which contributes to decreased cost and improved outcomes.^2,5-7,9,10 This study highlighted lesser-known areas of impact, such as the various specialty-specific services dermatology provides as well as the high rates of reported improvement following consultation. Future studies should continue to explore the field’s unique impact on hospitalized medicine as well as other avenues of care delivery, such as telemedicine, that may encourage dermatologists to participate in consultations and increase the volume of patients who may benefit from their care.

Dermatology is an often-underutilized resource in the hospital setting. As the health care landscape has evolved, so has the role of the inpatient dermatologist.^1-3 Structural changes in the health system and advances in therapies have shifted dermatology from an admitting service to an almost exclusively outpatient practice. Improved treatment modalities led to decreases in the number of patients requiring admission for chronic dermatoses, and outpatient clinics began offering therapies once limited to hospitals.^1,4 Inpatient dermatology consultations emerged and continue to have profound effects on hospitalized patients regardless of their reason for admission.^1-11

Inpatient dermatologists supply knowledge in areas primary medical teams lack, and there is evidence that dermatology consultations improve the quality of care while decreasing cost.^2,5-7 Establishing correct diagnoses, preventing exposure to unnecessary medications, and reducing hospitalization duration and readmission rates are a few ways dermatology consultations positively impact hospitalized patients.^2,5-7,9,10 This study highlights the role of the dermatologist in the care of hospitalized patients at a large academic medical center in an urban setting and reveals how consultation supports the efficiency and efficacy of other services.

Materials and Methods

Study Design—This single-institution, cross-sectional retrospective study included all hospitalized patients at the Thomas Jefferson University Hospital (Philadelphia, Pennsylvania), who received an inpatient dermatology consultation completed by physicians of Jefferson Dermatology Associates between January 1, 2019, and December 31, 2019. The institutional review board at Thomas Jefferson University approved this study.

Data Collection—A list of all inpatient dermatology consultations in 2019 was provided by Jefferson Dermatology Associates. Through a retrospective chart review, data regarding the consultations were collected from the electronic medical record (Epic Systems) and recorded into the Research Electronic Data Capture system. Data on patient demographics, the primary medical team, the dermatology evaluation, and the hospital course of the patient were collected.

Results

Patient Characteristics—Dermatology received 253 inpatient consultation requests during this time period; 53% of patients were female and 47% were male, with a mean age of 55 years. Most patients were White (57%), while 34% were Black. Five percent and 4% of patients were Asian and Hispanic or Latino, respectively (Table 1). The mean duration of hospitalization for all patients was 15 days, and the average number of days to discharge following the first encounter with dermatology was 10 days.

Requesting Team and Reason for Consultation—Internal medicine consulted dermatology most frequently (34% of all consultations), followed by emergency medicine (14%) and a variety of other services (Table 1). Most dermatology consultations were placed to assist in achieving a diagnosis of a cutaneous condition (77%), while a minority were to assist in the management of a previously diagnosed disease (22%). A small fraction of consultations (5%) were to complete full-body skin examinations (FBSEs) to rule out infection or malignancy in candidates for organ transplantation, left ventricular assist devices, or certain chemotherapies. One FBSE was conducted to search for a primary tumor in a patient diagnosed with metastatic melanoma.

Most Common Final Diagnoses and Consultation Impact—Table 2 lists the most common final diagnosis categories, as well as the effects of the consultation on diagnosis, management, biopsies, hospitalization, and clinical improvement as documented by the primary medical provider. The most common final diagnoses were inflammatory and autoimmune (39%), such as contact dermatitis and seborrheic dermatitis; infectious (23%), such as varicella (primary or zoster) and bacterial furunculosis; drug reactions (20%), such as morbilliform drug eruptions; vascular (8%), such as vasculitis and calciphylaxis; neoplastic (7%), such as keratinocyte carcinomas and leukemia cutis; and other (15%), such as xerosis, keratosis pilaris, and miliaria rubra.

Impact on Diagnosis—Fifty-six percent of all consultations resulted in a change in diagnosis. When dermatology was consulted specifically to assist in the diagnosis of a patient (195 consultations), the working diagnosis of the primary team was changed 69% of the time. Thirty-five of these consultation requests had no preliminary diagnosis, and the primary team listed the working diagnosis as either rash or a morphologic description of the lesion(s). Sixty-three percent of suspected drug eruptions ended with a diagnosis of a form of drug eruption, while 20% of consultations for suspected cellulitis or bacterial infections were confirmed to be cellulitis or soft tissue infections.

Impact on Management—Regardless of the reason for the consultation, most consultations (86%) resulted in a change in management. The remaining 14% consisted of FBSEs with benign findings; cases of cutaneous metastases and leukemia cutis managed by oncology; as well as select cases of purpura fulminans, postfebrile desquamation, and postinflammatory hyperpigmentation.

Changes in management included alterations in medications, requests for additional laboratory work or imaging, additional consultation requests, biopsies, or specific wound care instructions. Seventy-five percent of all consultations were given specific medication recommendations by dermatology. Most (61%) were recommended to be given a topical steroid, antibiotic, or both. However, 45% of all consultations were recommended to initiate a systemic medication, most commonly antihistamines, antibiotics, steroids, antivirals, or immunomodulators. Dermatology recommended discontinuing specific medications in 16% of all consultations, with antibiotics being the most frequent culprit (17 antibiotics discontinued), owing to drug eruptions or misdiagnosed infections. Vancomycin, piperacillin-tazobactam, and trimethoprim-sulfamethoxazole were the most frequently discontinued antibiotics.

Dermatology was consulted for assistance in management of previously diagnosed cutaneous conditions 56 times (22% of all consultations), often regarding complicated cases of hidradenitis suppurativa (9 cases), pyoderma gangrenosum (5 cases), bullous pemphigoid (4 cases), or erythroderma (4 cases). Most of these cases required a single dermatology encounter to provide recommendations (71%), and 21% required 1 additional follow-up. Sixty-three percent of patients consulted for management assistance were noted to have improvement in their cutaneous condition by time of discharge, as documented by the primary provider in the medical record.

Twenty-eight percent of all consultations required at least 1 biopsy. Seventy-two percent of all biopsies were consistent with the dermatologist’s working diagnosis or highest-ranked differential diagnosis, and 16% of biopsy results were consistent with the second- or third-ranked diagnosis. The primary teams requested a biopsy 38 times to assist in diagnosis, as documented in the progress note or consultation request. Only 21 of these consultations (55% of requests) received at least 1 biopsy, as the remaining consultations did not require a biopsy to establish a diagnosis. The most common final diagnoses of consultations receiving biopsies included drug eruptions (5), leukemia cutis (4), vasculopathies (4), vasculitis (4), and calciphylaxis (3).

Impact on Hospitalization and Efficacy—Dermatology performed 217 consultations regarding patients already admitted to the hospital, and 92% remained hospitalized either due to comorbidities or complicated cutaneous conditions following the consultation. The remaining 8% were cleared for discharge. Dermatology received 36 consultation requests from emergency medicine physicians. Fifty-three percent of these patients were admitted, while the remaining 47% were discharged from the emergency department or its observation unit following evaluation.

Fifty-one percent of all consultations were noted to have improvement in their cutaneous condition by the time of discharge, as noted in the physical examination, progress note, or discharge summary of the primary team. Thirty percent of cases remained stable, where improvement was not noted in in the medical record. Most of these cases involved keratinocyte carcinomas scheduled for outpatient excision, benign melanocytic nevi found on FBSE, and benign etiologies that led to immediate discharge following consultation. Three percent of all consultations were noted to have worsened following consultation, including cases of calciphylaxis, vasculopathies, and purpura fulminans, as well as patients who elected for palliative care and hospice. The cutaneous condition by the time of discharge could not be determined from the medical record in 16% of all consultations.

Eighty-five percent of all consultations required a single encounter with dermatology. An additional 10% required a single follow-up with dermatology, while only 5% of patients required 3 or more encounters. Notably, these cases included patients with 1 or more severe cutaneous diseases, such as Sweet syndrome, calciphylaxis, Stevens-Johnson syndrome/toxic epidermal necrolysis, and hidradenitis suppurativa.

Comment

Although dermatology often is viewed as an outpatient specialty, this study provides a glimpse into the ways inpatient dermatology consultations optimize the care of hospitalized patients. Most consultations involved assistance in diagnosing an unknown condition, but several regarded pre-existing skin disorders requiring management aid. As a variety of medical specialties requested consultations, dermatology was able to provide care to a diverse group of patients with conditions varying in complexity and severity. Several specialties benefited from niche dermatologic expertise: hematology and oncology frequently requested dermatology to assist in diagnosis and management of the toxic effects of chemotherapy, cutaneous metastasis, or suspected cutaneous infections in immunocompromised patients. Cardiology patients were frequently evaluated for potential malignancy or infection prior to heart transplantation and initiation of antirejection immunosuppressants. Dermatology was consulted to differentiate cutaneous manifestations of critical illness from underlying systemic disease in the intensive care unit, and patients presenting to the emergency department often were examined to determine if hospital admission was necessary, with 47% of these consultations resulting in a discharge following evaluation by a dermatologist.

Our results were consistent with prior studies^1,5,6 that have reported frequent changes in final diagnosis following dermatology consultation, with 69% of working diagnoses changed in this study when consultation was requested for diagnostic assistance. When dermatology was consulted for diagnostic assistance, several of these cases lacked a preliminary differential diagnosis. Although the absence of a documented differential diagnosis may not necessarily reflect a lack of suspicion for a particular etiology, 86% of all consultations included a ranked differential or working diagnosis either in the consultation request or progress note prior to consultation. The final diagnoses of consultations without a preliminary diagnosis varied from the mild and localized to systemic and severe, further suggesting these cases reflected knowledge gaps of the primary medical team.

Integration of dermatology into the care of hospitalized patients could provide an opportunity for education of primary medical teams. With frequent consultation, primary medical teams may become more comfortable diagnosing and managing common cutaneous conditions specific to their specialty or extended hospitalizations.

Several consultations were requested to aid in management of cases of hidradenitis suppurativa, pyoderma gangrenosum, or bullous pemphigoid that either failed outpatient therapy or were complicated by superinfections. Despite the ranges in complexity, the majority of all consultations required a single encounter and led to improvement by the time of discharge, demonstrating the efficacy and efficiency of inpatient dermatologists.

Dermatology consultations often led to changes in management involving medications and additional workup. Changes in management also extended to specific wound care instructions provided by dermatology, as expected for cases of Stevens-Johnson syndrome/toxic epidermal necrolysis, Sweet syndrome, hidradenitis suppurativa, and pyoderma gangrenosum. However, patients with the sequelae of extended hospitalizations, such as chronic wounds, pressure ulcers, and edema bullae, also benefited from this expertise.

When patients required a biopsy, the final diagnoses were consistent with the dermatologist’s number one differential diagnosis or top 3 differential diagnoses 72% and 88% of the time, respectively. Only 55% of cases where the primary team requested a biopsy ultimately required a biopsy, as many involved clinical diagnoses such as urticaria. Not only was dermatology accurate in their preliminary diagnoses, but they decreased cost and morbidity by avoiding unnecessary procedures.

This study provided additional evidence to support the integration of dermatology into the hospital setting for the benefit of patients, primary medical teams, and hospital systems. Dermatology offers high-value care through the efficient diagnosis and management of hospitalized patients, which contributes to decreased cost and improved outcomes.^2,5-7,9,10 This study highlighted lesser-known areas of impact, such as the various specialty-specific services dermatology provides as well as the high rates of reported improvement following consultation. Future studies should continue to explore the field’s unique impact on hospitalized medicine as well as other avenues of care delivery, such as telemedicine, that may encourage dermatologists to participate in consultations and increase the volume of patients who may benefit from their care.

Dermatology is an often-underutilized resource in the hospital setting. As the health care landscape has evolved, so has the role of the inpatient dermatologist.^1-3 Structural changes in the health system and advances in therapies have shifted dermatology from an admitting service to an almost exclusively outpatient practice. Improved treatment modalities led to decreases in the number of patients requiring admission for chronic dermatoses, and outpatient clinics began offering therapies once limited to hospitals.^1,4 Inpatient dermatology consultations emerged and continue to have profound effects on hospitalized patients regardless of their reason for admission.^1-11

Inpatient dermatologists supply knowledge in areas primary medical teams lack, and there is evidence that dermatology consultations improve the quality of care while decreasing cost.^2,5-7 Establishing correct diagnoses, preventing exposure to unnecessary medications, and reducing hospitalization duration and readmission rates are a few ways dermatology consultations positively impact hospitalized patients.^2,5-7,9,10 This study highlights the role of the dermatologist in the care of hospitalized patients at a large academic medical center in an urban setting and reveals how consultation supports the efficiency and efficacy of other services.

Materials and Methods

Study Design—This single-institution, cross-sectional retrospective study included all hospitalized patients at the Thomas Jefferson University Hospital (Philadelphia, Pennsylvania), who received an inpatient dermatology consultation completed by physicians of Jefferson Dermatology Associates between January 1, 2019, and December 31, 2019. The institutional review board at Thomas Jefferson University approved this study.

Data Collection—A list of all inpatient dermatology consultations in 2019 was provided by Jefferson Dermatology Associates. Through a retrospective chart review, data regarding the consultations were collected from the electronic medical record (Epic Systems) and recorded into the Research Electronic Data Capture system. Data on patient demographics, the primary medical team, the dermatology evaluation, and the hospital course of the patient were collected.

Results

Patient Characteristics—Dermatology received 253 inpatient consultation requests during this time period; 53% of patients were female and 47% were male, with a mean age of 55 years. Most patients were White (57%), while 34% were Black. Five percent and 4% of patients were Asian and Hispanic or Latino, respectively (Table 1). The mean duration of hospitalization for all patients was 15 days, and the average number of days to discharge following the first encounter with dermatology was 10 days.

Requesting Team and Reason for Consultation—Internal medicine consulted dermatology most frequently (34% of all consultations), followed by emergency medicine (14%) and a variety of other services (Table 1). Most dermatology consultations were placed to assist in achieving a diagnosis of a cutaneous condition (77%), while a minority were to assist in the management of a previously diagnosed disease (22%). A small fraction of consultations (5%) were to complete full-body skin examinations (FBSEs) to rule out infection or malignancy in candidates for organ transplantation, left ventricular assist devices, or certain chemotherapies. One FBSE was conducted to search for a primary tumor in a patient diagnosed with metastatic melanoma.

Most Common Final Diagnoses and Consultation Impact—Table 2 lists the most common final diagnosis categories, as well as the effects of the consultation on diagnosis, management, biopsies, hospitalization, and clinical improvement as documented by the primary medical provider. The most common final diagnoses were inflammatory and autoimmune (39%), such as contact dermatitis and seborrheic dermatitis; infectious (23%), such as varicella (primary or zoster) and bacterial furunculosis; drug reactions (20%), such as morbilliform drug eruptions; vascular (8%), such as vasculitis and calciphylaxis; neoplastic (7%), such as keratinocyte carcinomas and leukemia cutis; and other (15%), such as xerosis, keratosis pilaris, and miliaria rubra.

Impact on Diagnosis—Fifty-six percent of all consultations resulted in a change in diagnosis. When dermatology was consulted specifically to assist in the diagnosis of a patient (195 consultations), the working diagnosis of the primary team was changed 69% of the time. Thirty-five of these consultation requests had no preliminary diagnosis, and the primary team listed the working diagnosis as either rash or a morphologic description of the lesion(s). Sixty-three percent of suspected drug eruptions ended with a diagnosis of a form of drug eruption, while 20% of consultations for suspected cellulitis or bacterial infections were confirmed to be cellulitis or soft tissue infections.

Impact on Management—Regardless of the reason for the consultation, most consultations (86%) resulted in a change in management. The remaining 14% consisted of FBSEs with benign findings; cases of cutaneous metastases and leukemia cutis managed by oncology; as well as select cases of purpura fulminans, postfebrile desquamation, and postinflammatory hyperpigmentation.

Changes in management included alterations in medications, requests for additional laboratory work or imaging, additional consultation requests, biopsies, or specific wound care instructions. Seventy-five percent of all consultations were given specific medication recommendations by dermatology. Most (61%) were recommended to be given a topical steroid, antibiotic, or both. However, 45% of all consultations were recommended to initiate a systemic medication, most commonly antihistamines, antibiotics, steroids, antivirals, or immunomodulators. Dermatology recommended discontinuing specific medications in 16% of all consultations, with antibiotics being the most frequent culprit (17 antibiotics discontinued), owing to drug eruptions or misdiagnosed infections. Vancomycin, piperacillin-tazobactam, and trimethoprim-sulfamethoxazole were the most frequently discontinued antibiotics.

Dermatology was consulted for assistance in management of previously diagnosed cutaneous conditions 56 times (22% of all consultations), often regarding complicated cases of hidradenitis suppurativa (9 cases), pyoderma gangrenosum (5 cases), bullous pemphigoid (4 cases), or erythroderma (4 cases). Most of these cases required a single dermatology encounter to provide recommendations (71%), and 21% required 1 additional follow-up. Sixty-three percent of patients consulted for management assistance were noted to have improvement in their cutaneous condition by time of discharge, as documented by the primary provider in the medical record.

Twenty-eight percent of all consultations required at least 1 biopsy. Seventy-two percent of all biopsies were consistent with the dermatologist’s working diagnosis or highest-ranked differential diagnosis, and 16% of biopsy results were consistent with the second- or third-ranked diagnosis. The primary teams requested a biopsy 38 times to assist in diagnosis, as documented in the progress note or consultation request. Only 21 of these consultations (55% of requests) received at least 1 biopsy, as the remaining consultations did not require a biopsy to establish a diagnosis. The most common final diagnoses of consultations receiving biopsies included drug eruptions (5), leukemia cutis (4), vasculopathies (4), vasculitis (4), and calciphylaxis (3).

Impact on Hospitalization and Efficacy—Dermatology performed 217 consultations regarding patients already admitted to the hospital, and 92% remained hospitalized either due to comorbidities or complicated cutaneous conditions following the consultation. The remaining 8% were cleared for discharge. Dermatology received 36 consultation requests from emergency medicine physicians. Fifty-three percent of these patients were admitted, while the remaining 47% were discharged from the emergency department or its observation unit following evaluation.

Fifty-one percent of all consultations were noted to have improvement in their cutaneous condition by the time of discharge, as noted in the physical examination, progress note, or discharge summary of the primary team. Thirty percent of cases remained stable, where improvement was not noted in in the medical record. Most of these cases involved keratinocyte carcinomas scheduled for outpatient excision, benign melanocytic nevi found on FBSE, and benign etiologies that led to immediate discharge following consultation. Three percent of all consultations were noted to have worsened following consultation, including cases of calciphylaxis, vasculopathies, and purpura fulminans, as well as patients who elected for palliative care and hospice. The cutaneous condition by the time of discharge could not be determined from the medical record in 16% of all consultations.

Eighty-five percent of all consultations required a single encounter with dermatology. An additional 10% required a single follow-up with dermatology, while only 5% of patients required 3 or more encounters. Notably, these cases included patients with 1 or more severe cutaneous diseases, such as Sweet syndrome, calciphylaxis, Stevens-Johnson syndrome/toxic epidermal necrolysis, and hidradenitis suppurativa.

Comment

Although dermatology often is viewed as an outpatient specialty, this study provides a glimpse into the ways inpatient dermatology consultations optimize the care of hospitalized patients. Most consultations involved assistance in diagnosing an unknown condition, but several regarded pre-existing skin disorders requiring management aid. As a variety of medical specialties requested consultations, dermatology was able to provide care to a diverse group of patients with conditions varying in complexity and severity. Several specialties benefited from niche dermatologic expertise: hematology and oncology frequently requested dermatology to assist in diagnosis and management of the toxic effects of chemotherapy, cutaneous metastasis, or suspected cutaneous infections in immunocompromised patients. Cardiology patients were frequently evaluated for potential malignancy or infection prior to heart transplantation and initiation of antirejection immunosuppressants. Dermatology was consulted to differentiate cutaneous manifestations of critical illness from underlying systemic disease in the intensive care unit, and patients presenting to the emergency department often were examined to determine if hospital admission was necessary, with 47% of these consultations resulting in a discharge following evaluation by a dermatologist.

Our results were consistent with prior studies^1,5,6 that have reported frequent changes in final diagnosis following dermatology consultation, with 69% of working diagnoses changed in this study when consultation was requested for diagnostic assistance. When dermatology was consulted for diagnostic assistance, several of these cases lacked a preliminary differential diagnosis. Although the absence of a documented differential diagnosis may not necessarily reflect a lack of suspicion for a particular etiology, 86% of all consultations included a ranked differential or working diagnosis either in the consultation request or progress note prior to consultation. The final diagnoses of consultations without a preliminary diagnosis varied from the mild and localized to systemic and severe, further suggesting these cases reflected knowledge gaps of the primary medical team.

Integration of dermatology into the care of hospitalized patients could provide an opportunity for education of primary medical teams. With frequent consultation, primary medical teams may become more comfortable diagnosing and managing common cutaneous conditions specific to their specialty or extended hospitalizations.

Several consultations were requested to aid in management of cases of hidradenitis suppurativa, pyoderma gangrenosum, or bullous pemphigoid that either failed outpatient therapy or were complicated by superinfections. Despite the ranges in complexity, the majority of all consultations required a single encounter and led to improvement by the time of discharge, demonstrating the efficacy and efficiency of inpatient dermatologists.

Dermatology consultations often led to changes in management involving medications and additional workup. Changes in management also extended to specific wound care instructions provided by dermatology, as expected for cases of Stevens-Johnson syndrome/toxic epidermal necrolysis, Sweet syndrome, hidradenitis suppurativa, and pyoderma gangrenosum. However, patients with the sequelae of extended hospitalizations, such as chronic wounds, pressure ulcers, and edema bullae, also benefited from this expertise.

When patients required a biopsy, the final diagnoses were consistent with the dermatologist’s number one differential diagnosis or top 3 differential diagnoses 72% and 88% of the time, respectively. Only 55% of cases where the primary team requested a biopsy ultimately required a biopsy, as many involved clinical diagnoses such as urticaria. Not only was dermatology accurate in their preliminary diagnoses, but they decreased cost and morbidity by avoiding unnecessary procedures.

This study provided additional evidence to support the integration of dermatology into the hospital setting for the benefit of patients, primary medical teams, and hospital systems. Dermatology offers high-value care through the efficient diagnosis and management of hospitalized patients, which contributes to decreased cost and improved outcomes.^2,5-7,9,10 This study highlighted lesser-known areas of impact, such as the various specialty-specific services dermatology provides as well as the high rates of reported improvement following consultation. Future studies should continue to explore the field’s unique impact on hospitalized medicine as well as other avenues of care delivery, such as telemedicine, that may encourage dermatologists to participate in consultations and increase the volume of patients who may benefit from their care.

To the Editor:

A 59-year-old man presented with a severely pruritic rash on the legs, arms, abdomen, groin, and buttocks of 3 days’ duration. He reported subjective fever and chills. Prior to the appearance of the rash, the patient and his family had eaten shiitake mushrooms daily for 3 days. He denied any new medications in the last several months or any recent upper respiratory or gastrointestinal tract illnesses. His medical history included type 2 diabetes mellitus and diabetes-induced end-stage renal disease requiring home peritoneal dialysis. His long-term medications for diabetes mellitus, hypertension, benign prostatic hyperplasia, hyperlipidemia, and insomnia included amlodipine, atorvastatin, finasteride, gabapentin, insulin glargine, linagliptin, metoprolol, and mirtazapine.

Physical examination revealed an afebrile man with medium brown skin tone and diffuse, bright red, erythematous patches on the lower legs, axillae, medial forearms, lateral trunk, lower abdomen, and groin. There were distinct flagellate, linear, red patches on the lower legs (Figure 1). In addition, small clusters of 1- to 2-mm superficial pustules were present on the right upper medial thigh and left forearm with micropapules grouped in the skin folds.

A shave biopsy specimen from a pustule on the right upper medial thigh revealed spongiotic dermatitis with neutrophilic subcorneal pustule formation and frequent eosinophils (Figure 2). The dermis contained scattered mixed inflammatory cells including neutrophils, eosinophils, lymphocytes, and histiocytes (Figure 3). These histologic findings were consistent with acute generalized exanthematous pustulosis (AGEP). No biopsy was performed on the flagellate patches due to its clinically distinct presentation and well-established association with shiitake mushroom ingestion.

The patient was treated with triamcinolone ointment and systemic corticosteroids to reduce pruritus and quickly clear the lesions due to his comorbidities. He recovered completely within 1 week and had no evidence of postinflammatory hyperpigmentation from the flagellate dermatitis.

Flagellate dermatitis is an intensely pruritic dermatitis characterized by 1-mm, disseminated, erythematous papules in a linear grouped arrangement secondary to koebnerization due to the patient scratching. It was first described in 1977 by Nakamura.¹ Although it rarely is seen outside of China and Japan, there are well-established associations of flagellate dermatitis with bleomycin and shiitake mushroom (Lentinula edodes) ingestion. One key clinical difference between the two causes is that postinflammatory hyperpigmentation changes usually are seen with bleomycin-induced flagellate dermatitis and typically are not present with shiitake mushroom–induced flagellate dermatitis.² Following ingestion of shiitake mushrooms, the median time of onset of presentation typically is 24 hours but ranges from 12 hours to 5 days. Most patients completely recover by 3 weeks, with or without treatment.³ Although the pathogenesis of shiitake mushroom–induced flagellate dermatitis is not clear, the most common theory is a toxic reaction to lentinan, a polysaccharide isolated from shiitake mushrooms. However, type I and IV allergic hypersensitivities also have been supported by the time of onset, clearance, severe pruritus, benefit from steroids and antihistamines, and lack of grouped outbreaks in people exposed to shared meals containing shiitake mushrooms.^3,4 Furthermore, there is a case of patch test–confirmed allergic contact dermatitis to shiitake mushrooms, demonstrating a 1+ reaction at 96 hours to the cap of a shiitake mushroom but a negative pin-prick test at 20 minutes, suggesting type IV hypersensitivity.⁵ An additional case revealed a positive skin-prick test with formation of a 4-mm wheal and subsequent pruritic papules and vesicles appearing 48 to 72 hours later at the prick site.⁶ Subsequent cases have been reported in association with consumption of raw shiitake mushrooms, but cases have been reported after consumption of fully cooked mushrooms, which does not support a toxin-mediated theory, as cooking the mushroom before consumption likely would denature or change the structure of the suspected toxin.²

Acute generalized exanthematous pustulosis is a rare eruption that occurs due to ingestion of a causative agent, usually an antibiotic, and is characterized by the presence of fever and disseminated, erythematous, pinpoint, sterile pustules on the skin and mucous membranes. It affects 1 to 5 persons per million per year, with more than 90% of cases attributed to drug ingestion.⁷ Spontaneous resolution can be expected within 15 days of its onset; however, there is a mortality rate of up to 5% that occurs most often in those with severe comorbidities or in older patients, for whom systemic corticosteroid therapy may be justified.^7,8 A multinational case-control study conducted to evaluate the risk of AGEP associated with certain drugs revealed macrolides (namely pristinamycin); β-lactam antibiotics including penicillin, aminopenicillin, and cephalosporin; quinolones; hydroxychloroquine; anti-infective sulfonamides; terbinafine; and diltiazem as the most strongly associated culprits.⁹ Our patient’s flagellate dermatitis was unique in that it also showed histologic features of AGEP. The pathogenesis of drug-induced AGEP has been partially elucidated and involves activation of drug-specific CD4⁺ and CD8⁺ T cells that migrate to the skin and participate in apoptotic signaling of keratinocytes and recruitment of neutrophils and eosinophils, which form subcorneal sterile pustules.⁷ In a study of severe cutaneous adverse drug reactions, 50% (7/14) of patients with AGEP had positive patch tests to the causative agent.¹⁰ This T cell–dependent response explains why the condition responds to systemic corticosteroids. Additionally, our case report of shiitake mushroom–induced flagellate dermatitis with histologic features of AGEP suggests that the pathogenesis of flagellate dermatitis may be a T cell–mediated type IV hypersensitivity reaction. The time of onset, lack of grouped outbreaks in those sharing shiitake mushroom–containing meals, severe pruritus, lack of cases demonstrating an anaphylactic or wheal and flare response, benefit of steroids, and a case with histologic features of AGEP all lend support to this theory.

We report a case of shiitake mushroom–induced flagellate dermatitis with histologic features of AGEP. The time course, histologic features of AGEP, absence of new medications, and resolution with discontinuation of shiitake mushrooms lends support of the hypothesis that the pathogenesis of shiitake mushroom–induced flagellate dermatitis is similar to AGEP’s type IV hypersensitivity reaction. To further elucidate its pathogenesis, skin prick testing and patch testing with shiitake mushrooms in patients exhibiting shiitake mushroom–induced flagellate dermatitis may prove to be beneficial.

To the Editor:

A 59-year-old man presented with a severely pruritic rash on the legs, arms, abdomen, groin, and buttocks of 3 days’ duration. He reported subjective fever and chills. Prior to the appearance of the rash, the patient and his family had eaten shiitake mushrooms daily for 3 days. He denied any new medications in the last several months or any recent upper respiratory or gastrointestinal tract illnesses. His medical history included type 2 diabetes mellitus and diabetes-induced end-stage renal disease requiring home peritoneal dialysis. His long-term medications for diabetes mellitus, hypertension, benign prostatic hyperplasia, hyperlipidemia, and insomnia included amlodipine, atorvastatin, finasteride, gabapentin, insulin glargine, linagliptin, metoprolol, and mirtazapine.

Physical examination revealed an afebrile man with medium brown skin tone and diffuse, bright red, erythematous patches on the lower legs, axillae, medial forearms, lateral trunk, lower abdomen, and groin. There were distinct flagellate, linear, red patches on the lower legs (Figure 1). In addition, small clusters of 1- to 2-mm superficial pustules were present on the right upper medial thigh and left forearm with micropapules grouped in the skin folds.

A shave biopsy specimen from a pustule on the right upper medial thigh revealed spongiotic dermatitis with neutrophilic subcorneal pustule formation and frequent eosinophils (Figure 2). The dermis contained scattered mixed inflammatory cells including neutrophils, eosinophils, lymphocytes, and histiocytes (Figure 3). These histologic findings were consistent with acute generalized exanthematous pustulosis (AGEP). No biopsy was performed on the flagellate patches due to its clinically distinct presentation and well-established association with shiitake mushroom ingestion.

The patient was treated with triamcinolone ointment and systemic corticosteroids to reduce pruritus and quickly clear the lesions due to his comorbidities. He recovered completely within 1 week and had no evidence of postinflammatory hyperpigmentation from the flagellate dermatitis.

Flagellate dermatitis is an intensely pruritic dermatitis characterized by 1-mm, disseminated, erythematous papules in a linear grouped arrangement secondary to koebnerization due to the patient scratching. It was first described in 1977 by Nakamura.¹ Although it rarely is seen outside of China and Japan, there are well-established associations of flagellate dermatitis with bleomycin and shiitake mushroom (Lentinula edodes) ingestion. One key clinical difference between the two causes is that postinflammatory hyperpigmentation changes usually are seen with bleomycin-induced flagellate dermatitis and typically are not present with shiitake mushroom–induced flagellate dermatitis.² Following ingestion of shiitake mushrooms, the median time of onset of presentation typically is 24 hours but ranges from 12 hours to 5 days. Most patients completely recover by 3 weeks, with or without treatment.³ Although the pathogenesis of shiitake mushroom–induced flagellate dermatitis is not clear, the most common theory is a toxic reaction to lentinan, a polysaccharide isolated from shiitake mushrooms. However, type I and IV allergic hypersensitivities also have been supported by the time of onset, clearance, severe pruritus, benefit from steroids and antihistamines, and lack of grouped outbreaks in people exposed to shared meals containing shiitake mushrooms.^3,4 Furthermore, there is a case of patch test–confirmed allergic contact dermatitis to shiitake mushrooms, demonstrating a 1+ reaction at 96 hours to the cap of a shiitake mushroom but a negative pin-prick test at 20 minutes, suggesting type IV hypersensitivity.⁵ An additional case revealed a positive skin-prick test with formation of a 4-mm wheal and subsequent pruritic papules and vesicles appearing 48 to 72 hours later at the prick site.⁶ Subsequent cases have been reported in association with consumption of raw shiitake mushrooms, but cases have been reported after consumption of fully cooked mushrooms, which does not support a toxin-mediated theory, as cooking the mushroom before consumption likely would denature or change the structure of the suspected toxin.²

Acute generalized exanthematous pustulosis is a rare eruption that occurs due to ingestion of a causative agent, usually an antibiotic, and is characterized by the presence of fever and disseminated, erythematous, pinpoint, sterile pustules on the skin and mucous membranes. It affects 1 to 5 persons per million per year, with more than 90% of cases attributed to drug ingestion.⁷ Spontaneous resolution can be expected within 15 days of its onset; however, there is a mortality rate of up to 5% that occurs most often in those with severe comorbidities or in older patients, for whom systemic corticosteroid therapy may be justified.^7,8 A multinational case-control study conducted to evaluate the risk of AGEP associated with certain drugs revealed macrolides (namely pristinamycin); β-lactam antibiotics including penicillin, aminopenicillin, and cephalosporin; quinolones; hydroxychloroquine; anti-infective sulfonamides; terbinafine; and diltiazem as the most strongly associated culprits.⁹ Our patient’s flagellate dermatitis was unique in that it also showed histologic features of AGEP. The pathogenesis of drug-induced AGEP has been partially elucidated and involves activation of drug-specific CD4⁺ and CD8⁺ T cells that migrate to the skin and participate in apoptotic signaling of keratinocytes and recruitment of neutrophils and eosinophils, which form subcorneal sterile pustules.⁷ In a study of severe cutaneous adverse drug reactions, 50% (7/14) of patients with AGEP had positive patch tests to the causative agent.¹⁰ This T cell–dependent response explains why the condition responds to systemic corticosteroids. Additionally, our case report of shiitake mushroom–induced flagellate dermatitis with histologic features of AGEP suggests that the pathogenesis of flagellate dermatitis may be a T cell–mediated type IV hypersensitivity reaction. The time of onset, lack of grouped outbreaks in those sharing shiitake mushroom–containing meals, severe pruritus, lack of cases demonstrating an anaphylactic or wheal and flare response, benefit of steroids, and a case with histologic features of AGEP all lend support to this theory.

We report a case of shiitake mushroom–induced flagellate dermatitis with histologic features of AGEP. The time course, histologic features of AGEP, absence of new medications, and resolution with discontinuation of shiitake mushrooms lends support of the hypothesis that the pathogenesis of shiitake mushroom–induced flagellate dermatitis is similar to AGEP’s type IV hypersensitivity reaction. To further elucidate its pathogenesis, skin prick testing and patch testing with shiitake mushrooms in patients exhibiting shiitake mushroom–induced flagellate dermatitis may prove to be beneficial.

To the Editor:

A 59-year-old man presented with a severely pruritic rash on the legs, arms, abdomen, groin, and buttocks of 3 days’ duration. He reported subjective fever and chills. Prior to the appearance of the rash, the patient and his family had eaten shiitake mushrooms daily for 3 days. He denied any new medications in the last several months or any recent upper respiratory or gastrointestinal tract illnesses. His medical history included type 2 diabetes mellitus and diabetes-induced end-stage renal disease requiring home peritoneal dialysis. His long-term medications for diabetes mellitus, hypertension, benign prostatic hyperplasia, hyperlipidemia, and insomnia included amlodipine, atorvastatin, finasteride, gabapentin, insulin glargine, linagliptin, metoprolol, and mirtazapine.

Physical examination revealed an afebrile man with medium brown skin tone and diffuse, bright red, erythematous patches on the lower legs, axillae, medial forearms, lateral trunk, lower abdomen, and groin. There were distinct flagellate, linear, red patches on the lower legs (Figure 1). In addition, small clusters of 1- to 2-mm superficial pustules were present on the right upper medial thigh and left forearm with micropapules grouped in the skin folds.

A shave biopsy specimen from a pustule on the right upper medial thigh revealed spongiotic dermatitis with neutrophilic subcorneal pustule formation and frequent eosinophils (Figure 2). The dermis contained scattered mixed inflammatory cells including neutrophils, eosinophils, lymphocytes, and histiocytes (Figure 3). These histologic findings were consistent with acute generalized exanthematous pustulosis (AGEP). No biopsy was performed on the flagellate patches due to its clinically distinct presentation and well-established association with shiitake mushroom ingestion.

The patient was treated with triamcinolone ointment and systemic corticosteroids to reduce pruritus and quickly clear the lesions due to his comorbidities. He recovered completely within 1 week and had no evidence of postinflammatory hyperpigmentation from the flagellate dermatitis.

Flagellate dermatitis is an intensely pruritic dermatitis characterized by 1-mm, disseminated, erythematous papules in a linear grouped arrangement secondary to koebnerization due to the patient scratching. It was first described in 1977 by Nakamura.¹ Although it rarely is seen outside of China and Japan, there are well-established associations of flagellate dermatitis with bleomycin and shiitake mushroom (Lentinula edodes) ingestion. One key clinical difference between the two causes is that postinflammatory hyperpigmentation changes usually are seen with bleomycin-induced flagellate dermatitis and typically are not present with shiitake mushroom–induced flagellate dermatitis.² Following ingestion of shiitake mushrooms, the median time of onset of presentation typically is 24 hours but ranges from 12 hours to 5 days. Most patients completely recover by 3 weeks, with or without treatment.³ Although the pathogenesis of shiitake mushroom–induced flagellate dermatitis is not clear, the most common theory is a toxic reaction to lentinan, a polysaccharide isolated from shiitake mushrooms. However, type I and IV allergic hypersensitivities also have been supported by the time of onset, clearance, severe pruritus, benefit from steroids and antihistamines, and lack of grouped outbreaks in people exposed to shared meals containing shiitake mushrooms.^3,4 Furthermore, there is a case of patch test–confirmed allergic contact dermatitis to shiitake mushrooms, demonstrating a 1+ reaction at 96 hours to the cap of a shiitake mushroom but a negative pin-prick test at 20 minutes, suggesting type IV hypersensitivity.⁵ An additional case revealed a positive skin-prick test with formation of a 4-mm wheal and subsequent pruritic papules and vesicles appearing 48 to 72 hours later at the prick site.⁶ Subsequent cases have been reported in association with consumption of raw shiitake mushrooms, but cases have been reported after consumption of fully cooked mushrooms, which does not support a toxin-mediated theory, as cooking the mushroom before consumption likely would denature or change the structure of the suspected toxin.²

Acute generalized exanthematous pustulosis is a rare eruption that occurs due to ingestion of a causative agent, usually an antibiotic, and is characterized by the presence of fever and disseminated, erythematous, pinpoint, sterile pustules on the skin and mucous membranes. It affects 1 to 5 persons per million per year, with more than 90% of cases attributed to drug ingestion.⁷ Spontaneous resolution can be expected within 15 days of its onset; however, there is a mortality rate of up to 5% that occurs most often in those with severe comorbidities or in older patients, for whom systemic corticosteroid therapy may be justified.^7,8 A multinational case-control study conducted to evaluate the risk of AGEP associated with certain drugs revealed macrolides (namely pristinamycin); β-lactam antibiotics including penicillin, aminopenicillin, and cephalosporin; quinolones; hydroxychloroquine; anti-infective sulfonamides; terbinafine; and diltiazem as the most strongly associated culprits.⁹ Our patient’s flagellate dermatitis was unique in that it also showed histologic features of AGEP. The pathogenesis of drug-induced AGEP has been partially elucidated and involves activation of drug-specific CD4⁺ and CD8⁺ T cells that migrate to the skin and participate in apoptotic signaling of keratinocytes and recruitment of neutrophils and eosinophils, which form subcorneal sterile pustules.⁷ In a study of severe cutaneous adverse drug reactions, 50% (7/14) of patients with AGEP had positive patch tests to the causative agent.¹⁰ This T cell–dependent response explains why the condition responds to systemic corticosteroids. Additionally, our case report of shiitake mushroom–induced flagellate dermatitis with histologic features of AGEP suggests that the pathogenesis of flagellate dermatitis may be a T cell–mediated type IV hypersensitivity reaction. The time of onset, lack of grouped outbreaks in those sharing shiitake mushroom–containing meals, severe pruritus, lack of cases demonstrating an anaphylactic or wheal and flare response, benefit of steroids, and a case with histologic features of AGEP all lend support to this theory.

We report a case of shiitake mushroom–induced flagellate dermatitis with histologic features of AGEP. The time course, histologic features of AGEP, absence of new medications, and resolution with discontinuation of shiitake mushrooms lends support of the hypothesis that the pathogenesis of shiitake mushroom–induced flagellate dermatitis is similar to AGEP’s type IV hypersensitivity reaction. To further elucidate its pathogenesis, skin prick testing and patch testing with shiitake mushrooms in patients exhibiting shiitake mushroom–induced flagellate dermatitis may prove to be beneficial.

The Diagnosis: Dermatitis Neglecta

A punch biopsy of the abdomen revealed hyperkeratosis and mild papillomatosis (Figure), which can be seen in dermatitis neglecta (DN) and acanthosis nigricans (AN) as well as confluent and reticulated papillomatosis (CARP). Due to the patient’s history of mood and psychotic disorders, collateral information was obtained from the patient’s family, who reported that the patient had a depressed mood in the last few months and was not showering or caring for herself during this period. There was no additional personal or family history of skin disease. Clinical and histopathologic findings led to a diagnosis of DN. Following recommendations for daily cleansing with soap and water along with topical ammonium lactate, near-complete resolution of the rash was achieved in 3 weeks.

Dermatitis neglecta, or unwashed dermatosis, is a skin condition that occurs secondary to poor hygiene, which was first reported in 1995 by Poskitt et al.¹ Avoidance of washing in affected areas can be due to physical disability, pain after injury, neurological deficit, or psychologically induced fear or neglect. Sebum, sweat, corneocytes, and bacteria combine into compact adherent crusts of dirt, which appear as hyperkeratotic plaques with cornflakelike scale.^2,3 Despite its innate simplicity, DN is a diagnostic challenge, as it clinically and histologically mimics other dermatoses including AN, terra firmaforme dermatosis, and CARP.^2,4 Ultimately, the diagnosis of DN can be made when a history of poor hygiene is probable or elicited, and lesions can be removed with soap and water. Treatment of DN includes daily cleansing with soap and water; however, resistant lesions or extensive disease may require keratolytic agents, as in our patient.^2-4 In contrast, terra firma-forme dermatosis, which may look similar, is not due to poor hygiene, and the lesions typically are resistant to soap and water, classically requiring isopropyl alcohol for removal. Overall, maintained awareness of DN is imperative, as early diagnosis can avoid unnecessary biopsies and more complex treatment measures as well as facilitate coordination of care when additional medical or psychiatric concerns are present.

Although the diagnoses of DN and terra firma-forme dermatosis can be distinguished based on the patient’s clinical history and response to simple cleansing measures alone, the alternate diagnoses can be excluded based on different clinical distributions and response to other treatment modalities but sometimes may require clinicopathologic correlation for definitive diagnosis. Our patient had a biopsy diagnosis of psoriasiform dermatitis from an outside provider, but neither her clinical disease nor repeated histopathologic findings supported a diagnosis of psoriasis or other classic psoriasiform dermatoses such as contact dermatitis, dermatophyte/ candidal infection, seborrheic dermatitis, pityriasis rubra pilaris, pityriasis rosea, scabies, or syphilis.

It is imperative to exclude alternative diagnoses because they can have systemic implications and can misguide treatment, as was done initially with our patient. Psoriasis vulgaris in its classic form is a chronic inflammatory skin disease that manifests as sharply demarcated, erythematous plaques with overlying thick silvery scale; it has the additional histologic findings of neutrophilic spongiform pustules in the epidermis, tortuous blood vessels in the papillary dermis, and neutrophils and parakeratosis in the stratum corneum. In its benign form, AN is associated with endocrinopathies, most commonly obesity and insulin-resistant diabetes mellitus, and presents as hyperkeratotic, velvety, hyperpigmented plaques typically limited to the neck and axillae. Malignant AN spontaneously arises in association with systemic malignancy and can be extensive and generalized.⁵ Treatment of AN primarily focuses on resolution of the underlying systemic disease; however, cosmetic treatment with topical or oral retinoids may hasten resolution of cutaneous disease.⁶ Confluent and reticulated papillomatosis is characterized by reticulated hyperkeratotic plaques with a common distribution over the central and upper trunk. Unlike DN and AN, which may occur at any age, CARP typically is seen in adolescents and young adults.⁷ There is no evidence-based gold standard for the management of CARP; however, the successful use of various antibiotics, antifungals, and retinoids—alone or in combination—has been reported.⁸ Overall, compared to the other entities in the differential diagnosis, DN easily can be prevented with consistent use of soap and water and may be underreported given the asymptomatic nature of the disease and the typical patient population.

The Diagnosis: Dermatitis Neglecta

A punch biopsy of the abdomen revealed hyperkeratosis and mild papillomatosis (Figure), which can be seen in dermatitis neglecta (DN) and acanthosis nigricans (AN) as well as confluent and reticulated papillomatosis (CARP). Due to the patient’s history of mood and psychotic disorders, collateral information was obtained from the patient’s family, who reported that the patient had a depressed mood in the last few months and was not showering or caring for herself during this period. There was no additional personal or family history of skin disease. Clinical and histopathologic findings led to a diagnosis of DN. Following recommendations for daily cleansing with soap and water along with topical ammonium lactate, near-complete resolution of the rash was achieved in 3 weeks.

Dermatitis neglecta, or unwashed dermatosis, is a skin condition that occurs secondary to poor hygiene, which was first reported in 1995 by Poskitt et al.¹ Avoidance of washing in affected areas can be due to physical disability, pain after injury, neurological deficit, or psychologically induced fear or neglect. Sebum, sweat, corneocytes, and bacteria combine into compact adherent crusts of dirt, which appear as hyperkeratotic plaques with cornflakelike scale.^2,3 Despite its innate simplicity, DN is a diagnostic challenge, as it clinically and histologically mimics other dermatoses including AN, terra firmaforme dermatosis, and CARP.^2,4 Ultimately, the diagnosis of DN can be made when a history of poor hygiene is probable or elicited, and lesions can be removed with soap and water. Treatment of DN includes daily cleansing with soap and water; however, resistant lesions or extensive disease may require keratolytic agents, as in our patient.^2-4 In contrast, terra firma-forme dermatosis, which may look similar, is not due to poor hygiene, and the lesions typically are resistant to soap and water, classically requiring isopropyl alcohol for removal. Overall, maintained awareness of DN is imperative, as early diagnosis can avoid unnecessary biopsies and more complex treatment measures as well as facilitate coordination of care when additional medical or psychiatric concerns are present.

Although the diagnoses of DN and terra firma-forme dermatosis can be distinguished based on the patient’s clinical history and response to simple cleansing measures alone, the alternate diagnoses can be excluded based on different clinical distributions and response to other treatment modalities but sometimes may require clinicopathologic correlation for definitive diagnosis. Our patient had a biopsy diagnosis of psoriasiform dermatitis from an outside provider, but neither her clinical disease nor repeated histopathologic findings supported a diagnosis of psoriasis or other classic psoriasiform dermatoses such as contact dermatitis, dermatophyte/ candidal infection, seborrheic dermatitis, pityriasis rubra pilaris, pityriasis rosea, scabies, or syphilis.

It is imperative to exclude alternative diagnoses because they can have systemic implications and can misguide treatment, as was done initially with our patient. Psoriasis vulgaris in its classic form is a chronic inflammatory skin disease that manifests as sharply demarcated, erythematous plaques with overlying thick silvery scale; it has the additional histologic findings of neutrophilic spongiform pustules in the epidermis, tortuous blood vessels in the papillary dermis, and neutrophils and parakeratosis in the stratum corneum. In its benign form, AN is associated with endocrinopathies, most commonly obesity and insulin-resistant diabetes mellitus, and presents as hyperkeratotic, velvety, hyperpigmented plaques typically limited to the neck and axillae. Malignant AN spontaneously arises in association with systemic malignancy and can be extensive and generalized.⁵ Treatment of AN primarily focuses on resolution of the underlying systemic disease; however, cosmetic treatment with topical or oral retinoids may hasten resolution of cutaneous disease.⁶ Confluent and reticulated papillomatosis is characterized by reticulated hyperkeratotic plaques with a common distribution over the central and upper trunk. Unlike DN and AN, which may occur at any age, CARP typically is seen in adolescents and young adults.⁷ There is no evidence-based gold standard for the management of CARP; however, the successful use of various antibiotics, antifungals, and retinoids—alone or in combination—has been reported.⁸ Overall, compared to the other entities in the differential diagnosis, DN easily can be prevented with consistent use of soap and water and may be underreported given the asymptomatic nature of the disease and the typical patient population.

The Diagnosis: Dermatitis Neglecta

A punch biopsy of the abdomen revealed hyperkeratosis and mild papillomatosis (Figure), which can be seen in dermatitis neglecta (DN) and acanthosis nigricans (AN) as well as confluent and reticulated papillomatosis (CARP). Due to the patient’s history of mood and psychotic disorders, collateral information was obtained from the patient’s family, who reported that the patient had a depressed mood in the last few months and was not showering or caring for herself during this period. There was no additional personal or family history of skin disease. Clinical and histopathologic findings led to a diagnosis of DN. Following recommendations for daily cleansing with soap and water along with topical ammonium lactate, near-complete resolution of the rash was achieved in 3 weeks.

Dermatitis neglecta, or unwashed dermatosis, is a skin condition that occurs secondary to poor hygiene, which was first reported in 1995 by Poskitt et al.¹ Avoidance of washing in affected areas can be due to physical disability, pain after injury, neurological deficit, or psychologically induced fear or neglect. Sebum, sweat, corneocytes, and bacteria combine into compact adherent crusts of dirt, which appear as hyperkeratotic plaques with cornflakelike scale.^2,3 Despite its innate simplicity, DN is a diagnostic challenge, as it clinically and histologically mimics other dermatoses including AN, terra firmaforme dermatosis, and CARP.^2,4 Ultimately, the diagnosis of DN can be made when a history of poor hygiene is probable or elicited, and lesions can be removed with soap and water. Treatment of DN includes daily cleansing with soap and water; however, resistant lesions or extensive disease may require keratolytic agents, as in our patient.^2-4 In contrast, terra firma-forme dermatosis, which may look similar, is not due to poor hygiene, and the lesions typically are resistant to soap and water, classically requiring isopropyl alcohol for removal. Overall, maintained awareness of DN is imperative, as early diagnosis can avoid unnecessary biopsies and more complex treatment measures as well as facilitate coordination of care when additional medical or psychiatric concerns are present.

Although the diagnoses of DN and terra firma-forme dermatosis can be distinguished based on the patient’s clinical history and response to simple cleansing measures alone, the alternate diagnoses can be excluded based on different clinical distributions and response to other treatment modalities but sometimes may require clinicopathologic correlation for definitive diagnosis. Our patient had a biopsy diagnosis of psoriasiform dermatitis from an outside provider, but neither her clinical disease nor repeated histopathologic findings supported a diagnosis of psoriasis or other classic psoriasiform dermatoses such as contact dermatitis, dermatophyte/ candidal infection, seborrheic dermatitis, pityriasis rubra pilaris, pityriasis rosea, scabies, or syphilis.

It is imperative to exclude alternative diagnoses because they can have systemic implications and can misguide treatment, as was done initially with our patient. Psoriasis vulgaris in its classic form is a chronic inflammatory skin disease that manifests as sharply demarcated, erythematous plaques with overlying thick silvery scale; it has the additional histologic findings of neutrophilic spongiform pustules in the epidermis, tortuous blood vessels in the papillary dermis, and neutrophils and parakeratosis in the stratum corneum. In its benign form, AN is associated with endocrinopathies, most commonly obesity and insulin-resistant diabetes mellitus, and presents as hyperkeratotic, velvety, hyperpigmented plaques typically limited to the neck and axillae. Malignant AN spontaneously arises in association with systemic malignancy and can be extensive and generalized.⁵ Treatment of AN primarily focuses on resolution of the underlying systemic disease; however, cosmetic treatment with topical or oral retinoids may hasten resolution of cutaneous disease.⁶ Confluent and reticulated papillomatosis is characterized by reticulated hyperkeratotic plaques with a common distribution over the central and upper trunk. Unlike DN and AN, which may occur at any age, CARP typically is seen in adolescents and young adults.⁷ There is no evidence-based gold standard for the management of CARP; however, the successful use of various antibiotics, antifungals, and retinoids—alone or in combination—has been reported.⁸ Overall, compared to the other entities in the differential diagnosis, DN easily can be prevented with consistent use of soap and water and may be underreported given the asymptomatic nature of the disease and the typical patient population.