Case Letter

To the Editor:

Lichenoid drug eruptions are lichen planus–like hypersensitivity reactions induced by medications. These reactions are rare but cause irritation to the skin, as extreme pruritus is common. One review of 300 consecutive cases of drug eruptions submitted to dermatopathology revealed that 12% of cases were classified as lichenoid drug reactions.¹ Lichenoid dermatitis is characterized by extremely pruritic, scaly, eczematous or psoriasiform papules, often along the extensor surfaces and trunk.² The pruritic nature of the rash can negatively impact quality of life. Treatment typically involves discontinuation of the offending medication, although complete resolution can take months, even after the drug is stopped. Although there have been some data suggesting that topical and/or oral corticosteroids can help with resolution, the rash can persist even with steroid treatment.²

The histopathologic findings of lichenoid drug eruptions show lichen planus–like changes such as hyperkeratosis, irregular acanthosis, and lichenoid interface dermatitis. Accordingly, idiopathic lichen planus is an important differential diagnosis for lichenoid drug eruptions; however, compared to idiopathic lichen planus, lichenoid drug eruptions are more likely to be associated with eosinophils and parakeratosis.^1,3 In some cases, the histopathologic distinction between the 2 conditions is impossible, and clinical history needs to be considered to make a diagnosis.¹ Drugs known to cause lichenoid drug reactions more commonly include angiotensin-converting enzyme inhibitors, beta blockers, thiazides, gold, penicillamine, and antimalarials.² Lichenoid drug eruptions also have been documented in patients taking the second-generation nonsteroidal androgen receptor antagonist enzalutamide, which is used for the treatment of prostate cancer.⁴ More recently, the newer second-generation nonsteroidal androgen receptor antagonist apalutamide has been implicated in several cases of lichenoid drug eruptions.^5,6

We present a case of an apalutamide-induced lichenoid drug eruption that was resistant to dose reduction and required discontinuation of treatment due to the negative impact on the patient’s quality of life. Once the rash resolved, the patient transitioned to enzalutamide without any adverse events (AEs).

A 72-year-old man with a history of metastatic prostate cancer (stage IVB) presented to the dermatology clinic with a 4-month history of a dry itchy rash on the face, chest, back, and legs that had developed 2 to 3 months after oncology started him on apalutamide. The patient initially received apalutamide 240 mg/d, which was reduced by his oncologist 3 months later to 180 mg/d following the appearance of the rash. Then apalutamide was held as he awaited improvement of the rash.

One week after the apalutamide was held, the patient presented to dermatology. He reported that he had tried over-the-counter ammonium lactate 12% lotion twice daily when the rash first developed without improvement. When the apalutamide was held, oncology prescribed mupirocin ointment 2% 3 times daily which yielded minimal relief. On physical examination, widespread lichenified papules and plaques were noted on the face, chest, back, and legs (Figure 1). Dermatology initially prescribed triamcinolone ointment 0.1% twice daily. A 4-mm punch biopsy specimen of the upper back revealed a lichenoid interface dermatitis with numerous eosinophils compatible with a lichenoid hypersensitivity reaction (Figure 2). Considering the clinical and histologic findings, a diagnosis of lichenoid drug eruption secondary to apalutamide treatment was made.

To the Editor:

Lichenoid drug eruptions are lichen planus–like hypersensitivity reactions induced by medications. These reactions are rare but cause irritation to the skin, as extreme pruritus is common. One review of 300 consecutive cases of drug eruptions submitted to dermatopathology revealed that 12% of cases were classified as lichenoid drug reactions.¹ Lichenoid dermatitis is characterized by extremely pruritic, scaly, eczematous or psoriasiform papules, often along the extensor surfaces and trunk.² The pruritic nature of the rash can negatively impact quality of life. Treatment typically involves discontinuation of the offending medication, although complete resolution can take months, even after the drug is stopped. Although there have been some data suggesting that topical and/or oral corticosteroids can help with resolution, the rash can persist even with steroid treatment.²

The histopathologic findings of lichenoid drug eruptions show lichen planus–like changes such as hyperkeratosis, irregular acanthosis, and lichenoid interface dermatitis. Accordingly, idiopathic lichen planus is an important differential diagnosis for lichenoid drug eruptions; however, compared to idiopathic lichen planus, lichenoid drug eruptions are more likely to be associated with eosinophils and parakeratosis.^1,3 In some cases, the histopathologic distinction between the 2 conditions is impossible, and clinical history needs to be considered to make a diagnosis.¹ Drugs known to cause lichenoid drug reactions more commonly include angiotensin-converting enzyme inhibitors, beta blockers, thiazides, gold, penicillamine, and antimalarials.² Lichenoid drug eruptions also have been documented in patients taking the second-generation nonsteroidal androgen receptor antagonist enzalutamide, which is used for the treatment of prostate cancer.⁴ More recently, the newer second-generation nonsteroidal androgen receptor antagonist apalutamide has been implicated in several cases of lichenoid drug eruptions.^5,6

We present a case of an apalutamide-induced lichenoid drug eruption that was resistant to dose reduction and required discontinuation of treatment due to the negative impact on the patient’s quality of life. Once the rash resolved, the patient transitioned to enzalutamide without any adverse events (AEs).

A 72-year-old man with a history of metastatic prostate cancer (stage IVB) presented to the dermatology clinic with a 4-month history of a dry itchy rash on the face, chest, back, and legs that had developed 2 to 3 months after oncology started him on apalutamide. The patient initially received apalutamide 240 mg/d, which was reduced by his oncologist 3 months later to 180 mg/d following the appearance of the rash. Then apalutamide was held as he awaited improvement of the rash.

One week after the apalutamide was held, the patient presented to dermatology. He reported that he had tried over-the-counter ammonium lactate 12% lotion twice daily when the rash first developed without improvement. When the apalutamide was held, oncology prescribed mupirocin ointment 2% 3 times daily which yielded minimal relief. On physical examination, widespread lichenified papules and plaques were noted on the face, chest, back, and legs (Figure 1). Dermatology initially prescribed triamcinolone ointment 0.1% twice daily. A 4-mm punch biopsy specimen of the upper back revealed a lichenoid interface dermatitis with numerous eosinophils compatible with a lichenoid hypersensitivity reaction (Figure 2). Considering the clinical and histologic findings, a diagnosis of lichenoid drug eruption secondary to apalutamide treatment was made.

To the Editor:

Lichenoid drug eruptions are lichen planus–like hypersensitivity reactions induced by medications. These reactions are rare but cause irritation to the skin, as extreme pruritus is common. One review of 300 consecutive cases of drug eruptions submitted to dermatopathology revealed that 12% of cases were classified as lichenoid drug reactions.¹ Lichenoid dermatitis is characterized by extremely pruritic, scaly, eczematous or psoriasiform papules, often along the extensor surfaces and trunk.² The pruritic nature of the rash can negatively impact quality of life. Treatment typically involves discontinuation of the offending medication, although complete resolution can take months, even after the drug is stopped. Although there have been some data suggesting that topical and/or oral corticosteroids can help with resolution, the rash can persist even with steroid treatment.²

The histopathologic findings of lichenoid drug eruptions show lichen planus–like changes such as hyperkeratosis, irregular acanthosis, and lichenoid interface dermatitis. Accordingly, idiopathic lichen planus is an important differential diagnosis for lichenoid drug eruptions; however, compared to idiopathic lichen planus, lichenoid drug eruptions are more likely to be associated with eosinophils and parakeratosis.^1,3 In some cases, the histopathologic distinction between the 2 conditions is impossible, and clinical history needs to be considered to make a diagnosis.¹ Drugs known to cause lichenoid drug reactions more commonly include angiotensin-converting enzyme inhibitors, beta blockers, thiazides, gold, penicillamine, and antimalarials.² Lichenoid drug eruptions also have been documented in patients taking the second-generation nonsteroidal androgen receptor antagonist enzalutamide, which is used for the treatment of prostate cancer.⁴ More recently, the newer second-generation nonsteroidal androgen receptor antagonist apalutamide has been implicated in several cases of lichenoid drug eruptions.^5,6

We present a case of an apalutamide-induced lichenoid drug eruption that was resistant to dose reduction and required discontinuation of treatment due to the negative impact on the patient’s quality of life. Once the rash resolved, the patient transitioned to enzalutamide without any adverse events (AEs).

A 72-year-old man with a history of metastatic prostate cancer (stage IVB) presented to the dermatology clinic with a 4-month history of a dry itchy rash on the face, chest, back, and legs that had developed 2 to 3 months after oncology started him on apalutamide. The patient initially received apalutamide 240 mg/d, which was reduced by his oncologist 3 months later to 180 mg/d following the appearance of the rash. Then apalutamide was held as he awaited improvement of the rash.

One week after the apalutamide was held, the patient presented to dermatology. He reported that he had tried over-the-counter ammonium lactate 12% lotion twice daily when the rash first developed without improvement. When the apalutamide was held, oncology prescribed mupirocin ointment 2% 3 times daily which yielded minimal relief. On physical examination, widespread lichenified papules and plaques were noted on the face, chest, back, and legs (Figure 1). Dermatology initially prescribed triamcinolone ointment 0.1% twice daily. A 4-mm punch biopsy specimen of the upper back revealed a lichenoid interface dermatitis with numerous eosinophils compatible with a lichenoid hypersensitivity reaction (Figure 2). Considering the clinical and histologic findings, a diagnosis of lichenoid drug eruption secondary to apalutamide treatment was made.

To the Editor:

Scleroderma is a chronic autoimmune connective tissue disease that results in excessive collagen deposition in the skin and other organs throughout the body. On its own or in the setting of mixed connective tissue disease, scleroderma can result in systemic or localized symptoms that can limit patients’ functional capabilities, cause pain and discomfort, and reduce self-esteem—all negatively impacting patients’ quality of life.^1,2 Neck sclerosis is a common manifestation of scleroderma. There is no curative treatment for scleroderma; thus, therapy is focused on slowing disease progression and improving quality of life. We present a case of neck sclerosis in a 44-year-old woman with scleroderma that was successfully treated with botulinum toxin (BTX) type A injection, resulting in improved skin laxity and appearance with high patient satisfaction. Our case demonstrates the potential positive effects of BTX treatment in patients with features of sclerosis or fibrosis, particularly in the neck region.

A 44-year-old woman presented to the dermatology clinic for treatment of thickened neck skin with stiffness and tightness that had been present for months to years. She had a history of mixed connective tissue disease (MCTD)(positive anti-ribonucleoprotein, anti–Sjögren syndrome–related antigen, and anti-Smith antibodies) with features of scleroderma and polyarthritis. The patient currently was taking sulfasalazine for the polyarthritis; she previously had taken hydroxychloroquine but discontinued treatment due to ineffectiveness. She was not taking any topical or systemic medications for scleroderma. On physical examination, the skin on the anterior neck appeared thickened with shiny patches (Figure 1). Pinching the skin in the affected area demonstrated ­sclerosis with high tension.

Scleroderma is a chronic connective tissue disorder that results in excessive collagen deposition in the skin and other organs throughout the body.⁴ Although the etiology is unknown, scleroderma develops when overactivation of the immune system leads to CD4⁺ T-lymphocyte infiltration in the skin, along with the release of profibrotic interleukins and growth factors, resulting in fibrosis.⁴ Subtypes include localized scleroderma (morphea), limited cutaneous systemic sclerosis (formerly known as CREST [calcinosis, RP, esophageal dysmotility, sclerodactyly, and telangiectasia] syndrome), diffuse cutaneous systemic sclerosis, and systemic sclerosis sine scleroderma.⁵ Scleroderma is associated with positive antinuclear antibodies and HLA II alleles (HLA-DR2 and HLA-DR5).

On its own or in the setting of MCTD, scleroderma can result in systemic or localized symptoms. Overall, the most common symptom is RP.⁵ Localized scleroderma and limited cutaneous systemic sclerosis manifest with symptoms of the skin and underlying tissues. Diffuse cutaneous systemic sclerosis involves cutaneous and visceral symptoms, including lung, esophageal, and vascular involvement.⁶ Similar to MCTD, scleroderma is most prevalent in middle-aged females,⁷ though it occurs at a higher rate and with a more severe disease course in Black patients.⁸

A highly sensitive and specific test for scleroderma that can aid in diagnosis is the neck sign—tightening of the skin of the neck when the head extends.^9,10 In one study, the neck sign was positive in more than 90% of patients with scleroderma and negative for control patients and those with primary RP.⁹ Thus, neck sclerosis is a common manifestation of scleroderma for which patients may seek treatment.

While there is no curative treatment for scleroderma, skin manifestations can be treated with mycophenolate mofetil or methotrexate.⁵ Systemic treatments may be recommended if the patient has additional symptoms, such as azathioprine for myositis/arthritis and cyclophosphamide for interstitial lung disease.⁵ However, it is important to note that these medications are associated with risk for gastrointestinal upset, mouth sores, fatigue, or other complications.

Botulinum toxin is a bacterial protein toxin and neuromodulator that inhibits neurotransmitter release by cleaving SNARE proteins at peripheral nerve terminal junctions.¹¹ It has been used in a variety of dermatologic and nondermatologic conditions, including migraines, hyperhidrosis, contractures, scars, and overactive bladder. It also has been used in aesthetics for facial rejuvenation and minimization of wrinkle appearance. Dermatologists and rheumatologists have successfully used BTX to treat primary and secondary RP—the most common symptom of scleroderma—due to its vasodilatation properties.¹² Although our patient did not have RP, use of BTX to treat other features of scleroderma, including en coup de sabre, thoracic outlet syndrome, dyspareunia, gastroparesis, pterygium inversum unguis, and dysphagia has been documented.^13-18 An in vivo mouse study that examined the possible mechanism for BTX as a treatment in scleroderma found that BTX injections significantly decreased dermal thickness and inflammation in fibrosis (P<.05). An analysis of oxidative stress and mRNA expression showed that BTX may treat fibrosis by suppressing oxidative stress and inflammatory cells, resulting in decreased apoptosis and oxidant-induced intracellular accumulation of reactive oxygen species.¹⁹ Another animal study demonstrated the positive effects of BTX treatment for fibrosis of the bladder in rats.²⁰ In one case report, a female patient with scleroderma and facial fibrosis received perioral BTX injections for cosmetic purposes but also observed improvement in mouth constriction, demonstrating the potential efficacy of BTX for facial fibrosis.²¹

Our case demonstrates the potential positive effects of BTX treatment in patients with features of sclerosis or fibrosis, particularly in the neck region. We recommend assessing the efficacy of the initial BTX treatment after 2 to 3 weeks, with additional injections as needed to achieve the patient’s desired level of comfort and appearance at approximately 3-month intervals (aligning with the expected duration of efficacy of BTX).²² Our patient experienced considerable relief and high satisfaction with BTX treatment. Given the limitations of sclerosis treatments and the unwanted adverse-effect profile of systemic treatments, BTX injections may be a preferrable treatment option for cutaneous manifestations of ­scleroderma among patients. Future studies with larger patient populations and a control group are warranted to further explore the use of BTX for the dermatologic treatment of scleroderma.

To the Editor:

Scleroderma is a chronic autoimmune connective tissue disease that results in excessive collagen deposition in the skin and other organs throughout the body. On its own or in the setting of mixed connective tissue disease, scleroderma can result in systemic or localized symptoms that can limit patients’ functional capabilities, cause pain and discomfort, and reduce self-esteem—all negatively impacting patients’ quality of life.^1,2 Neck sclerosis is a common manifestation of scleroderma. There is no curative treatment for scleroderma; thus, therapy is focused on slowing disease progression and improving quality of life. We present a case of neck sclerosis in a 44-year-old woman with scleroderma that was successfully treated with botulinum toxin (BTX) type A injection, resulting in improved skin laxity and appearance with high patient satisfaction. Our case demonstrates the potential positive effects of BTX treatment in patients with features of sclerosis or fibrosis, particularly in the neck region.

A 44-year-old woman presented to the dermatology clinic for treatment of thickened neck skin with stiffness and tightness that had been present for months to years. She had a history of mixed connective tissue disease (MCTD)(positive anti-ribonucleoprotein, anti–Sjögren syndrome–related antigen, and anti-Smith antibodies) with features of scleroderma and polyarthritis. The patient currently was taking sulfasalazine for the polyarthritis; she previously had taken hydroxychloroquine but discontinued treatment due to ineffectiveness. She was not taking any topical or systemic medications for scleroderma. On physical examination, the skin on the anterior neck appeared thickened with shiny patches (Figure 1). Pinching the skin in the affected area demonstrated ­sclerosis with high tension.

Scleroderma is a chronic connective tissue disorder that results in excessive collagen deposition in the skin and other organs throughout the body.⁴ Although the etiology is unknown, scleroderma develops when overactivation of the immune system leads to CD4⁺ T-lymphocyte infiltration in the skin, along with the release of profibrotic interleukins and growth factors, resulting in fibrosis.⁴ Subtypes include localized scleroderma (morphea), limited cutaneous systemic sclerosis (formerly known as CREST [calcinosis, RP, esophageal dysmotility, sclerodactyly, and telangiectasia] syndrome), diffuse cutaneous systemic sclerosis, and systemic sclerosis sine scleroderma.⁵ Scleroderma is associated with positive antinuclear antibodies and HLA II alleles (HLA-DR2 and HLA-DR5).

On its own or in the setting of MCTD, scleroderma can result in systemic or localized symptoms. Overall, the most common symptom is RP.⁵ Localized scleroderma and limited cutaneous systemic sclerosis manifest with symptoms of the skin and underlying tissues. Diffuse cutaneous systemic sclerosis involves cutaneous and visceral symptoms, including lung, esophageal, and vascular involvement.⁶ Similar to MCTD, scleroderma is most prevalent in middle-aged females,⁷ though it occurs at a higher rate and with a more severe disease course in Black patients.⁸

A highly sensitive and specific test for scleroderma that can aid in diagnosis is the neck sign—tightening of the skin of the neck when the head extends.^9,10 In one study, the neck sign was positive in more than 90% of patients with scleroderma and negative for control patients and those with primary RP.⁹ Thus, neck sclerosis is a common manifestation of scleroderma for which patients may seek treatment.

While there is no curative treatment for scleroderma, skin manifestations can be treated with mycophenolate mofetil or methotrexate.⁵ Systemic treatments may be recommended if the patient has additional symptoms, such as azathioprine for myositis/arthritis and cyclophosphamide for interstitial lung disease.⁵ However, it is important to note that these medications are associated with risk for gastrointestinal upset, mouth sores, fatigue, or other complications.

Botulinum toxin is a bacterial protein toxin and neuromodulator that inhibits neurotransmitter release by cleaving SNARE proteins at peripheral nerve terminal junctions.¹¹ It has been used in a variety of dermatologic and nondermatologic conditions, including migraines, hyperhidrosis, contractures, scars, and overactive bladder. It also has been used in aesthetics for facial rejuvenation and minimization of wrinkle appearance. Dermatologists and rheumatologists have successfully used BTX to treat primary and secondary RP—the most common symptom of scleroderma—due to its vasodilatation properties.¹² Although our patient did not have RP, use of BTX to treat other features of scleroderma, including en coup de sabre, thoracic outlet syndrome, dyspareunia, gastroparesis, pterygium inversum unguis, and dysphagia has been documented.^13-18 An in vivo mouse study that examined the possible mechanism for BTX as a treatment in scleroderma found that BTX injections significantly decreased dermal thickness and inflammation in fibrosis (P<.05). An analysis of oxidative stress and mRNA expression showed that BTX may treat fibrosis by suppressing oxidative stress and inflammatory cells, resulting in decreased apoptosis and oxidant-induced intracellular accumulation of reactive oxygen species.¹⁹ Another animal study demonstrated the positive effects of BTX treatment for fibrosis of the bladder in rats.²⁰ In one case report, a female patient with scleroderma and facial fibrosis received perioral BTX injections for cosmetic purposes but also observed improvement in mouth constriction, demonstrating the potential efficacy of BTX for facial fibrosis.²¹

Our case demonstrates the potential positive effects of BTX treatment in patients with features of sclerosis or fibrosis, particularly in the neck region. We recommend assessing the efficacy of the initial BTX treatment after 2 to 3 weeks, with additional injections as needed to achieve the patient’s desired level of comfort and appearance at approximately 3-month intervals (aligning with the expected duration of efficacy of BTX).²² Our patient experienced considerable relief and high satisfaction with BTX treatment. Given the limitations of sclerosis treatments and the unwanted adverse-effect profile of systemic treatments, BTX injections may be a preferrable treatment option for cutaneous manifestations of ­scleroderma among patients. Future studies with larger patient populations and a control group are warranted to further explore the use of BTX for the dermatologic treatment of scleroderma.

To the Editor:

Scleroderma is a chronic autoimmune connective tissue disease that results in excessive collagen deposition in the skin and other organs throughout the body. On its own or in the setting of mixed connective tissue disease, scleroderma can result in systemic or localized symptoms that can limit patients’ functional capabilities, cause pain and discomfort, and reduce self-esteem—all negatively impacting patients’ quality of life.^1,2 Neck sclerosis is a common manifestation of scleroderma. There is no curative treatment for scleroderma; thus, therapy is focused on slowing disease progression and improving quality of life. We present a case of neck sclerosis in a 44-year-old woman with scleroderma that was successfully treated with botulinum toxin (BTX) type A injection, resulting in improved skin laxity and appearance with high patient satisfaction. Our case demonstrates the potential positive effects of BTX treatment in patients with features of sclerosis or fibrosis, particularly in the neck region.

A 44-year-old woman presented to the dermatology clinic for treatment of thickened neck skin with stiffness and tightness that had been present for months to years. She had a history of mixed connective tissue disease (MCTD)(positive anti-ribonucleoprotein, anti–Sjögren syndrome–related antigen, and anti-Smith antibodies) with features of scleroderma and polyarthritis. The patient currently was taking sulfasalazine for the polyarthritis; she previously had taken hydroxychloroquine but discontinued treatment due to ineffectiveness. She was not taking any topical or systemic medications for scleroderma. On physical examination, the skin on the anterior neck appeared thickened with shiny patches (Figure 1). Pinching the skin in the affected area demonstrated ­sclerosis with high tension.

Scleroderma is a chronic connective tissue disorder that results in excessive collagen deposition in the skin and other organs throughout the body.⁴ Although the etiology is unknown, scleroderma develops when overactivation of the immune system leads to CD4⁺ T-lymphocyte infiltration in the skin, along with the release of profibrotic interleukins and growth factors, resulting in fibrosis.⁴ Subtypes include localized scleroderma (morphea), limited cutaneous systemic sclerosis (formerly known as CREST [calcinosis, RP, esophageal dysmotility, sclerodactyly, and telangiectasia] syndrome), diffuse cutaneous systemic sclerosis, and systemic sclerosis sine scleroderma.⁵ Scleroderma is associated with positive antinuclear antibodies and HLA II alleles (HLA-DR2 and HLA-DR5).

On its own or in the setting of MCTD, scleroderma can result in systemic or localized symptoms. Overall, the most common symptom is RP.⁵ Localized scleroderma and limited cutaneous systemic sclerosis manifest with symptoms of the skin and underlying tissues. Diffuse cutaneous systemic sclerosis involves cutaneous and visceral symptoms, including lung, esophageal, and vascular involvement.⁶ Similar to MCTD, scleroderma is most prevalent in middle-aged females,⁷ though it occurs at a higher rate and with a more severe disease course in Black patients.⁸

A highly sensitive and specific test for scleroderma that can aid in diagnosis is the neck sign—tightening of the skin of the neck when the head extends.^9,10 In one study, the neck sign was positive in more than 90% of patients with scleroderma and negative for control patients and those with primary RP.⁹ Thus, neck sclerosis is a common manifestation of scleroderma for which patients may seek treatment.

While there is no curative treatment for scleroderma, skin manifestations can be treated with mycophenolate mofetil or methotrexate.⁵ Systemic treatments may be recommended if the patient has additional symptoms, such as azathioprine for myositis/arthritis and cyclophosphamide for interstitial lung disease.⁵ However, it is important to note that these medications are associated with risk for gastrointestinal upset, mouth sores, fatigue, or other complications.

Botulinum toxin is a bacterial protein toxin and neuromodulator that inhibits neurotransmitter release by cleaving SNARE proteins at peripheral nerve terminal junctions.¹¹ It has been used in a variety of dermatologic and nondermatologic conditions, including migraines, hyperhidrosis, contractures, scars, and overactive bladder. It also has been used in aesthetics for facial rejuvenation and minimization of wrinkle appearance. Dermatologists and rheumatologists have successfully used BTX to treat primary and secondary RP—the most common symptom of scleroderma—due to its vasodilatation properties.¹² Although our patient did not have RP, use of BTX to treat other features of scleroderma, including en coup de sabre, thoracic outlet syndrome, dyspareunia, gastroparesis, pterygium inversum unguis, and dysphagia has been documented.^13-18 An in vivo mouse study that examined the possible mechanism for BTX as a treatment in scleroderma found that BTX injections significantly decreased dermal thickness and inflammation in fibrosis (P<.05). An analysis of oxidative stress and mRNA expression showed that BTX may treat fibrosis by suppressing oxidative stress and inflammatory cells, resulting in decreased apoptosis and oxidant-induced intracellular accumulation of reactive oxygen species.¹⁹ Another animal study demonstrated the positive effects of BTX treatment for fibrosis of the bladder in rats.²⁰ In one case report, a female patient with scleroderma and facial fibrosis received perioral BTX injections for cosmetic purposes but also observed improvement in mouth constriction, demonstrating the potential efficacy of BTX for facial fibrosis.²¹

Our case demonstrates the potential positive effects of BTX treatment in patients with features of sclerosis or fibrosis, particularly in the neck region. We recommend assessing the efficacy of the initial BTX treatment after 2 to 3 weeks, with additional injections as needed to achieve the patient’s desired level of comfort and appearance at approximately 3-month intervals (aligning with the expected duration of efficacy of BTX).²² Our patient experienced considerable relief and high satisfaction with BTX treatment. Given the limitations of sclerosis treatments and the unwanted adverse-effect profile of systemic treatments, BTX injections may be a preferrable treatment option for cutaneous manifestations of ­scleroderma among patients. Future studies with larger patient populations and a control group are warranted to further explore the use of BTX for the dermatologic treatment of scleroderma.

To the Editor:

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome—a severe cutaneous adverse drug reaction—is characterized by a cutaneous rash and systemic upset in the form of various internal organ and hematologic disturbances. This delayed and idiosyncratic syndrome went by several names, including anticonvulsant hypersensitivity syndrome, before Bocquet et al¹ proposed the term DRESS syndrome.

Phenytoin, a hydantoin derivative used in neurology, was implicated in 41% of cases of DRESS syndrome in a study of 100 patients conducted in southern India.^2,3 While DRESS syndrome is a newer name, the clinical picture of DRESS secondary to phenytoin use remains similar in that it manifests with a morbilliform rash and systemic upset. We sought to describe the clinical and laboratory characteristics of phenytoin-induced DRESS syndrome in this case series.

The analysis included 23 patients with DRESS syndrome secondary to phenytoin use who presented to a tertiary care institution in North India between July 2021 and December 2022, satisfied the European Registry of Severe Cutaneous Adverse Reaction (RegiSCAR) criteria,⁴ and achieved a DRESS diagnostic score of more than 1. The mean age of the patients was 44 years (range, 14–74 years). There was a slight female predominance with a male to female ratio of 0.9:1. More than half of the patients (52.2% [12/23]) presented directly to the dermatology outpatient department; the remaining patients were referred from other departments (47.8% [11/23]). Patients primarily were receiving phenytoin for neurologic indications. Specific reasons included antiseizure prophylaxis following a traffic accident (34.8% [8/23]); epilepsy (26.1% [6/23]); and neoplastic (17.4% [4/23]), vascular (17.4% [4/23]), and infectious (4.3% [1/23]) causes. The mean latency period from drug intake to symptom onset was 29 days (range, 6–62 days), and the mean illness duration was 9 days (range, 1–45 days).

The majority of patients experienced pruritus (91.3% [21/23]) and fever (74.0% [17/23]), and all initially had a rash. Maculopapular morphology was seen in all patients. Erythema multiforme–like (17.4% [4/23]), erythrodermic (17.4% [4/23]), and vesicular (13.0% [3/23]) rashes also were documented (Figure 1). The trunk (100% [23/23]) and extremities (95.7% [22/23]) were involved most often, followed by the palms and soles (56.5% [13/23]). The mean total body surface area affected was 73.65%. Only 7 patients (30.4%) had mucosal ­involvement; nonhemorrhagic cheilitis was the most common manifestation.

To the Editor:

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome—a severe cutaneous adverse drug reaction—is characterized by a cutaneous rash and systemic upset in the form of various internal organ and hematologic disturbances. This delayed and idiosyncratic syndrome went by several names, including anticonvulsant hypersensitivity syndrome, before Bocquet et al¹ proposed the term DRESS syndrome.

Phenytoin, a hydantoin derivative used in neurology, was implicated in 41% of cases of DRESS syndrome in a study of 100 patients conducted in southern India.^2,3 While DRESS syndrome is a newer name, the clinical picture of DRESS secondary to phenytoin use remains similar in that it manifests with a morbilliform rash and systemic upset. We sought to describe the clinical and laboratory characteristics of phenytoin-induced DRESS syndrome in this case series.

The analysis included 23 patients with DRESS syndrome secondary to phenytoin use who presented to a tertiary care institution in North India between July 2021 and December 2022, satisfied the European Registry of Severe Cutaneous Adverse Reaction (RegiSCAR) criteria,⁴ and achieved a DRESS diagnostic score of more than 1. The mean age of the patients was 44 years (range, 14–74 years). There was a slight female predominance with a male to female ratio of 0.9:1. More than half of the patients (52.2% [12/23]) presented directly to the dermatology outpatient department; the remaining patients were referred from other departments (47.8% [11/23]). Patients primarily were receiving phenytoin for neurologic indications. Specific reasons included antiseizure prophylaxis following a traffic accident (34.8% [8/23]); epilepsy (26.1% [6/23]); and neoplastic (17.4% [4/23]), vascular (17.4% [4/23]), and infectious (4.3% [1/23]) causes. The mean latency period from drug intake to symptom onset was 29 days (range, 6–62 days), and the mean illness duration was 9 days (range, 1–45 days).

The majority of patients experienced pruritus (91.3% [21/23]) and fever (74.0% [17/23]), and all initially had a rash. Maculopapular morphology was seen in all patients. Erythema multiforme–like (17.4% [4/23]), erythrodermic (17.4% [4/23]), and vesicular (13.0% [3/23]) rashes also were documented (Figure 1). The trunk (100% [23/23]) and extremities (95.7% [22/23]) were involved most often, followed by the palms and soles (56.5% [13/23]). The mean total body surface area affected was 73.65%. Only 7 patients (30.4%) had mucosal ­involvement; nonhemorrhagic cheilitis was the most common manifestation.

To the Editor:

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome—a severe cutaneous adverse drug reaction—is characterized by a cutaneous rash and systemic upset in the form of various internal organ and hematologic disturbances. This delayed and idiosyncratic syndrome went by several names, including anticonvulsant hypersensitivity syndrome, before Bocquet et al¹ proposed the term DRESS syndrome.

Phenytoin, a hydantoin derivative used in neurology, was implicated in 41% of cases of DRESS syndrome in a study of 100 patients conducted in southern India.^2,3 While DRESS syndrome is a newer name, the clinical picture of DRESS secondary to phenytoin use remains similar in that it manifests with a morbilliform rash and systemic upset. We sought to describe the clinical and laboratory characteristics of phenytoin-induced DRESS syndrome in this case series.

The analysis included 23 patients with DRESS syndrome secondary to phenytoin use who presented to a tertiary care institution in North India between July 2021 and December 2022, satisfied the European Registry of Severe Cutaneous Adverse Reaction (RegiSCAR) criteria,⁴ and achieved a DRESS diagnostic score of more than 1. The mean age of the patients was 44 years (range, 14–74 years). There was a slight female predominance with a male to female ratio of 0.9:1. More than half of the patients (52.2% [12/23]) presented directly to the dermatology outpatient department; the remaining patients were referred from other departments (47.8% [11/23]). Patients primarily were receiving phenytoin for neurologic indications. Specific reasons included antiseizure prophylaxis following a traffic accident (34.8% [8/23]); epilepsy (26.1% [6/23]); and neoplastic (17.4% [4/23]), vascular (17.4% [4/23]), and infectious (4.3% [1/23]) causes. The mean latency period from drug intake to symptom onset was 29 days (range, 6–62 days), and the mean illness duration was 9 days (range, 1–45 days).

The majority of patients experienced pruritus (91.3% [21/23]) and fever (74.0% [17/23]), and all initially had a rash. Maculopapular morphology was seen in all patients. Erythema multiforme–like (17.4% [4/23]), erythrodermic (17.4% [4/23]), and vesicular (13.0% [3/23]) rashes also were documented (Figure 1). The trunk (100% [23/23]) and extremities (95.7% [22/23]) were involved most often, followed by the palms and soles (56.5% [13/23]). The mean total body surface area affected was 73.65%. Only 7 patients (30.4%) had mucosal ­involvement; nonhemorrhagic cheilitis was the most common manifestation.

To the Editor:

Gonococcal infections, which are caused by the sexually transmitted, gram-negative diplococcus Neisseria gonorrhoeae, are a current and increasing threat to public health. Between 2012 and 2021, the rate of gonococcal infection in the United States increased 137.8% in men and 64.9% in women,¹ with an estimated 1.5 million new gonococcal infections occurring each year in the United States as of 2021.²Neisseria gonorrhoeae is the second most common bacterial sexually transmitted infection (STI), and patients with gonococcal infection frequently are coinfected with Chlamydia trachomatis, which is the most common bacterial STI. Uncomplicated gonococcal infection (also known as gonorrhea) most commonly causes asymptomatic cervicovaginal infection in women and symptomatic urethral infection in men.² Other uncomplicated manifestations include rectal infection, which can be asymptomatic or manifest with anal pruritus, anal discharge, or tenesmus, and oropharyngeal infection, which can be asymptomatic or manifest with throat pain. If uncomplicated gonococcal infections are left untreated or are incompletely treated, serious complications including septic arthritis, myositis, osteomyelitis, myocarditis, endocarditis, and meningitis might occur.^2-5 Ascending, locally invasive infections can cause epididymitis or pelvic inflammatory disease, which is an important cause of infertility in women.^2,3 Gonococcal conjunctivitis also can occur, particularly when neonates are exposed to bacteria during vaginal delivery. Although rare, gonococcal bacteria can disseminate widely, with an estimated 0.5% to 3% of uncomplicated gonococcal infections progressing to disseminated gonococcal infection (DGI).^3-6 Because DGI can mimic other systemic conditions, including a variety of bacterial and viral infections as well as inflammatory conditions, it can be difficult to diagnose without a high index of clinical suspicion. We present a case of DGI diagnosed based on dermatologic expertise and pharyngeal molecular testing.

A 30-year-old man presented to the emergency department with a rash on the extremeities as well as emesis, fever, sore throat, and severe arthralgia in the wrists, hands, knees, and feet of 2 days’ duration. The patient also had experienced several months of dysuria. He reported daily use of the recreational drug ketamine, multiple new male sexual partners, and unprotected oral and receptive anal sex in recent months. He denied any history of STIs. Physical examination demonstrated tender edematous wrists and fingers, papulovesicles on erythematous bases on the palms, and purpuric macules scattered on the legs (Figure 1). The patient also had tonsillar edema with notable white tonsillar exudate.

To the Editor:

Gonococcal infections, which are caused by the sexually transmitted, gram-negative diplococcus Neisseria gonorrhoeae, are a current and increasing threat to public health. Between 2012 and 2021, the rate of gonococcal infection in the United States increased 137.8% in men and 64.9% in women,¹ with an estimated 1.5 million new gonococcal infections occurring each year in the United States as of 2021.²Neisseria gonorrhoeae is the second most common bacterial sexually transmitted infection (STI), and patients with gonococcal infection frequently are coinfected with Chlamydia trachomatis, which is the most common bacterial STI. Uncomplicated gonococcal infection (also known as gonorrhea) most commonly causes asymptomatic cervicovaginal infection in women and symptomatic urethral infection in men.² Other uncomplicated manifestations include rectal infection, which can be asymptomatic or manifest with anal pruritus, anal discharge, or tenesmus, and oropharyngeal infection, which can be asymptomatic or manifest with throat pain. If uncomplicated gonococcal infections are left untreated or are incompletely treated, serious complications including septic arthritis, myositis, osteomyelitis, myocarditis, endocarditis, and meningitis might occur.^2-5 Ascending, locally invasive infections can cause epididymitis or pelvic inflammatory disease, which is an important cause of infertility in women.^2,3 Gonococcal conjunctivitis also can occur, particularly when neonates are exposed to bacteria during vaginal delivery. Although rare, gonococcal bacteria can disseminate widely, with an estimated 0.5% to 3% of uncomplicated gonococcal infections progressing to disseminated gonococcal infection (DGI).^3-6 Because DGI can mimic other systemic conditions, including a variety of bacterial and viral infections as well as inflammatory conditions, it can be difficult to diagnose without a high index of clinical suspicion. We present a case of DGI diagnosed based on dermatologic expertise and pharyngeal molecular testing.

A 30-year-old man presented to the emergency department with a rash on the extremeities as well as emesis, fever, sore throat, and severe arthralgia in the wrists, hands, knees, and feet of 2 days’ duration. The patient also had experienced several months of dysuria. He reported daily use of the recreational drug ketamine, multiple new male sexual partners, and unprotected oral and receptive anal sex in recent months. He denied any history of STIs. Physical examination demonstrated tender edematous wrists and fingers, papulovesicles on erythematous bases on the palms, and purpuric macules scattered on the legs (Figure 1). The patient also had tonsillar edema with notable white tonsillar exudate.

To the Editor:

Gonococcal infections, which are caused by the sexually transmitted, gram-negative diplococcus Neisseria gonorrhoeae, are a current and increasing threat to public health. Between 2012 and 2021, the rate of gonococcal infection in the United States increased 137.8% in men and 64.9% in women,¹ with an estimated 1.5 million new gonococcal infections occurring each year in the United States as of 2021.²Neisseria gonorrhoeae is the second most common bacterial sexually transmitted infection (STI), and patients with gonococcal infection frequently are coinfected with Chlamydia trachomatis, which is the most common bacterial STI. Uncomplicated gonococcal infection (also known as gonorrhea) most commonly causes asymptomatic cervicovaginal infection in women and symptomatic urethral infection in men.² Other uncomplicated manifestations include rectal infection, which can be asymptomatic or manifest with anal pruritus, anal discharge, or tenesmus, and oropharyngeal infection, which can be asymptomatic or manifest with throat pain. If uncomplicated gonococcal infections are left untreated or are incompletely treated, serious complications including septic arthritis, myositis, osteomyelitis, myocarditis, endocarditis, and meningitis might occur.^2-5 Ascending, locally invasive infections can cause epididymitis or pelvic inflammatory disease, which is an important cause of infertility in women.^2,3 Gonococcal conjunctivitis also can occur, particularly when neonates are exposed to bacteria during vaginal delivery. Although rare, gonococcal bacteria can disseminate widely, with an estimated 0.5% to 3% of uncomplicated gonococcal infections progressing to disseminated gonococcal infection (DGI).^3-6 Because DGI can mimic other systemic conditions, including a variety of bacterial and viral infections as well as inflammatory conditions, it can be difficult to diagnose without a high index of clinical suspicion. We present a case of DGI diagnosed based on dermatologic expertise and pharyngeal molecular testing.

A 30-year-old man presented to the emergency department with a rash on the extremeities as well as emesis, fever, sore throat, and severe arthralgia in the wrists, hands, knees, and feet of 2 days’ duration. The patient also had experienced several months of dysuria. He reported daily use of the recreational drug ketamine, multiple new male sexual partners, and unprotected oral and receptive anal sex in recent months. He denied any history of STIs. Physical examination demonstrated tender edematous wrists and fingers, papulovesicles on erythematous bases on the palms, and purpuric macules scattered on the legs (Figure 1). The patient also had tonsillar edema with notable white tonsillar exudate.

To the Editor:

Histopathologic analysis of debulk specimens in Mohs micrographic surgery (MMS) may augment identification of high-risk factors in cutaneous squamous cell carcinoma (cSCC), which may warrant tumor upstaging.¹ Intratumor location has not been studied when looking at these high-risk factors. Herein, we report 4 cSCCs initially categorized as well differentiated that were reclassified as moderate to poorly differentiated on analysis of debulk specimens obtained via shave removal.

An 80-year-old man (patient 1) presented with a tender 2-cm erythematous plaque with dried hemorrhagic crusting on the frontal scalp. He had a history of nonmelanoma skin cancers. A biopsy revealed a ­well-differentiated cSCC, which was upgraded from a T2a tumor to T2b during MMS due to galea involvement. Debulk analysis revealed moderate to poorly differentiated cSCC, with the least-differentiated cells at the deep margin (Figure 1A). Given T2b staging, baseline imaging and radiation therapy were recommended.

To the Editor:

Histopathologic analysis of debulk specimens in Mohs micrographic surgery (MMS) may augment identification of high-risk factors in cutaneous squamous cell carcinoma (cSCC), which may warrant tumor upstaging.¹ Intratumor location has not been studied when looking at these high-risk factors. Herein, we report 4 cSCCs initially categorized as well differentiated that were reclassified as moderate to poorly differentiated on analysis of debulk specimens obtained via shave removal.

An 80-year-old man (patient 1) presented with a tender 2-cm erythematous plaque with dried hemorrhagic crusting on the frontal scalp. He had a history of nonmelanoma skin cancers. A biopsy revealed a ­well-differentiated cSCC, which was upgraded from a T2a tumor to T2b during MMS due to galea involvement. Debulk analysis revealed moderate to poorly differentiated cSCC, with the least-differentiated cells at the deep margin (Figure 1A). Given T2b staging, baseline imaging and radiation therapy were recommended.

To the Editor:

Histopathologic analysis of debulk specimens in Mohs micrographic surgery (MMS) may augment identification of high-risk factors in cutaneous squamous cell carcinoma (cSCC), which may warrant tumor upstaging.¹ Intratumor location has not been studied when looking at these high-risk factors. Herein, we report 4 cSCCs initially categorized as well differentiated that were reclassified as moderate to poorly differentiated on analysis of debulk specimens obtained via shave removal.

An 80-year-old man (patient 1) presented with a tender 2-cm erythematous plaque with dried hemorrhagic crusting on the frontal scalp. He had a history of nonmelanoma skin cancers. A biopsy revealed a ­well-differentiated cSCC, which was upgraded from a T2a tumor to T2b during MMS due to galea involvement. Debulk analysis revealed moderate to poorly differentiated cSCC, with the least-differentiated cells at the deep margin (Figure 1A). Given T2b staging, baseline imaging and radiation therapy were recommended.

To the Editor:

Mutations of the BRAF protein kinase gene are implicated in a variety of malignancies.¹BRAF mutations in malignancies cause the mitogen-activated protein kinase (MAPK) pathway to become constitutively active, which results in unchecked cellular proliferation,^2,3 making the BRAF mutation an attractive target for inhibition with pharmacologic agents to potentially halt cancer growth.⁴ Vemurafenib—the first selective BRAF inhibitor used in clinical practice—initially was approved by the US Food and Drug Administration in 2011. The approval of dabrafenib followed in 2013 and most recently encorafenib in 2018.⁵

Although targeted treatment of BRAF-mutated malignancies with BRAF inhibitors has become common, it often is associated with cutaneous adverse events (AEs), such as rash, pruritus, photosensitivity, actinic keratosis, and verrucous keratosis. Some reports demonstrate these events in up to 95% of patients undergoing BRAF inhibitor treatment.⁶ In several cases the eruption of verrucous keratoses is among the most common cutaneous AEs seen among patients receiving BRAF inhibitor treatment.^5-7

In general, lesions can appear days to months after therapy is initiated and may resolve after switching to dual therapy with a MEK inhibitor or with complete cessation of BRAF inhibitor therapy.^5,7,8 One case of spontaneous resolution of vemurafenib-associated panniculitis during ongoing BRAF inhibitor therapy has been reported⁹; however, spontaneous resolution of cutaneous AEs is uncommon. Herein, we describe verrucous keratoses in a patient undergoing treatment with encorafenib that resolved spontaneously despite ongoing BRAF inhibitor therapy.

A 61-year-old woman presented to the emergency department with pain in the right lower quadrant. Computed tomography (CT) of the abdomen and pelvis revealed a large ovarian mass. Subsequent bloodwork revealed elevated carcinoembryonic antigen levels. The patient underwent a hysterectomy, bilateral salpingo-oophorectomy, omentectomy, right hemicolectomy with ileotransverse side-to-side anastomosis, right pelvic lymph node reduction, and complete cytoreduction. Histopathology revealed an adenocarcinoma of the cecum with tumor invasion into the visceral peritoneum and metastases to the left ovary, fallopian tube, and omentum. A BRAF V600E mutation was detected.

Two months after the initial presentation, the patient started her first cycle of chemotherapy with a combination of folinic acid, fluorouracil, and oxaliplatin. She completed 11 cycles of this regimen, then was switched to capecitabine and oxaliplatin for an additional 2 cycles due to insurance concerns. At the end of treatment, there was no evidence of disease on CT, thus the patient was followed with observation. However, she presented 10 months later to the emergency department with abdominal pain, and CT revealed new lesions in the liver that were concerning for potential metastases. She started oral encorafenib 300 mg/d and intravenous cetuximab 500 mg weekly; after 1 week, encorafenib was reduced to 150 mg/d due to nausea and loss of appetite. Within 2 weeks of starting treatment, the patient reported the relatively abrupt appearance of more than 50 small papules across the shoulders and back (Figure 1A). She was referred to dermatology, and shave biopsies of 2 lesions—one from the left anterior thigh, the other from the right posterior shoulder—revealed verrucous keratosis pathology (Figure 2). At this time, encorafenib was increased again to 300 mg/d as the patient had been tolerating the reduced dose. She continued to report the appearance of new lesions for the next 3 months, after which the lesions were stable for approximately 2 months. By 2.5 months after initiation of therapy, the patient had ­undergone CT demonstrating resolution of the liver lesions. At 5 months of therapy, the patient reported a stable to slightly reduced number of skin lesions but had begun to experience worsening joint pain, and the dosage of encorafenib was reduced to 225 mg/d. At 7 months of therapy, the dosage was further reduced to 150 mg/d due to persistent arthralgia. A follow-up examination at 10 months of therapy showed improvement in the number and size of the verrucous keratoses, and near resolution was seen by 14 months after the initial onset of the lesions (Figure 1B). At 20 months after initial onset, only 1 remaining verrucous keratosis was identified on physical examination and biopsy. The patient had continued a regimen of encorafenib 150 mg/d and weekly intravenous 500 mg cetuximab up to this point. Over the entire time period that the patient was seen, up to 12 lesions located in high-friction areas had become irritated and were treated with cryotherapy, but this contributed only minorly to the patient’s overall presentation.

To the Editor:

Mutations of the BRAF protein kinase gene are implicated in a variety of malignancies.¹BRAF mutations in malignancies cause the mitogen-activated protein kinase (MAPK) pathway to become constitutively active, which results in unchecked cellular proliferation,^2,3 making the BRAF mutation an attractive target for inhibition with pharmacologic agents to potentially halt cancer growth.⁴ Vemurafenib—the first selective BRAF inhibitor used in clinical practice—initially was approved by the US Food and Drug Administration in 2011. The approval of dabrafenib followed in 2013 and most recently encorafenib in 2018.⁵

Although targeted treatment of BRAF-mutated malignancies with BRAF inhibitors has become common, it often is associated with cutaneous adverse events (AEs), such as rash, pruritus, photosensitivity, actinic keratosis, and verrucous keratosis. Some reports demonstrate these events in up to 95% of patients undergoing BRAF inhibitor treatment.⁶ In several cases the eruption of verrucous keratoses is among the most common cutaneous AEs seen among patients receiving BRAF inhibitor treatment.^5-7

In general, lesions can appear days to months after therapy is initiated and may resolve after switching to dual therapy with a MEK inhibitor or with complete cessation of BRAF inhibitor therapy.^5,7,8 One case of spontaneous resolution of vemurafenib-associated panniculitis during ongoing BRAF inhibitor therapy has been reported⁹; however, spontaneous resolution of cutaneous AEs is uncommon. Herein, we describe verrucous keratoses in a patient undergoing treatment with encorafenib that resolved spontaneously despite ongoing BRAF inhibitor therapy.

A 61-year-old woman presented to the emergency department with pain in the right lower quadrant. Computed tomography (CT) of the abdomen and pelvis revealed a large ovarian mass. Subsequent bloodwork revealed elevated carcinoembryonic antigen levels. The patient underwent a hysterectomy, bilateral salpingo-oophorectomy, omentectomy, right hemicolectomy with ileotransverse side-to-side anastomosis, right pelvic lymph node reduction, and complete cytoreduction. Histopathology revealed an adenocarcinoma of the cecum with tumor invasion into the visceral peritoneum and metastases to the left ovary, fallopian tube, and omentum. A BRAF V600E mutation was detected.

Two months after the initial presentation, the patient started her first cycle of chemotherapy with a combination of folinic acid, fluorouracil, and oxaliplatin. She completed 11 cycles of this regimen, then was switched to capecitabine and oxaliplatin for an additional 2 cycles due to insurance concerns. At the end of treatment, there was no evidence of disease on CT, thus the patient was followed with observation. However, she presented 10 months later to the emergency department with abdominal pain, and CT revealed new lesions in the liver that were concerning for potential metastases. She started oral encorafenib 300 mg/d and intravenous cetuximab 500 mg weekly; after 1 week, encorafenib was reduced to 150 mg/d due to nausea and loss of appetite. Within 2 weeks of starting treatment, the patient reported the relatively abrupt appearance of more than 50 small papules across the shoulders and back (Figure 1A). She was referred to dermatology, and shave biopsies of 2 lesions—one from the left anterior thigh, the other from the right posterior shoulder—revealed verrucous keratosis pathology (Figure 2). At this time, encorafenib was increased again to 300 mg/d as the patient had been tolerating the reduced dose. She continued to report the appearance of new lesions for the next 3 months, after which the lesions were stable for approximately 2 months. By 2.5 months after initiation of therapy, the patient had ­undergone CT demonstrating resolution of the liver lesions. At 5 months of therapy, the patient reported a stable to slightly reduced number of skin lesions but had begun to experience worsening joint pain, and the dosage of encorafenib was reduced to 225 mg/d. At 7 months of therapy, the dosage was further reduced to 150 mg/d due to persistent arthralgia. A follow-up examination at 10 months of therapy showed improvement in the number and size of the verrucous keratoses, and near resolution was seen by 14 months after the initial onset of the lesions (Figure 1B). At 20 months after initial onset, only 1 remaining verrucous keratosis was identified on physical examination and biopsy. The patient had continued a regimen of encorafenib 150 mg/d and weekly intravenous 500 mg cetuximab up to this point. Over the entire time period that the patient was seen, up to 12 lesions located in high-friction areas had become irritated and were treated with cryotherapy, but this contributed only minorly to the patient’s overall presentation.

To the Editor:

Mutations of the BRAF protein kinase gene are implicated in a variety of malignancies.¹BRAF mutations in malignancies cause the mitogen-activated protein kinase (MAPK) pathway to become constitutively active, which results in unchecked cellular proliferation,^2,3 making the BRAF mutation an attractive target for inhibition with pharmacologic agents to potentially halt cancer growth.⁴ Vemurafenib—the first selective BRAF inhibitor used in clinical practice—initially was approved by the US Food and Drug Administration in 2011. The approval of dabrafenib followed in 2013 and most recently encorafenib in 2018.⁵

Although targeted treatment of BRAF-mutated malignancies with BRAF inhibitors has become common, it often is associated with cutaneous adverse events (AEs), such as rash, pruritus, photosensitivity, actinic keratosis, and verrucous keratosis. Some reports demonstrate these events in up to 95% of patients undergoing BRAF inhibitor treatment.⁶ In several cases the eruption of verrucous keratoses is among the most common cutaneous AEs seen among patients receiving BRAF inhibitor treatment.^5-7

In general, lesions can appear days to months after therapy is initiated and may resolve after switching to dual therapy with a MEK inhibitor or with complete cessation of BRAF inhibitor therapy.^5,7,8 One case of spontaneous resolution of vemurafenib-associated panniculitis during ongoing BRAF inhibitor therapy has been reported⁹; however, spontaneous resolution of cutaneous AEs is uncommon. Herein, we describe verrucous keratoses in a patient undergoing treatment with encorafenib that resolved spontaneously despite ongoing BRAF inhibitor therapy.

A 61-year-old woman presented to the emergency department with pain in the right lower quadrant. Computed tomography (CT) of the abdomen and pelvis revealed a large ovarian mass. Subsequent bloodwork revealed elevated carcinoembryonic antigen levels. The patient underwent a hysterectomy, bilateral salpingo-oophorectomy, omentectomy, right hemicolectomy with ileotransverse side-to-side anastomosis, right pelvic lymph node reduction, and complete cytoreduction. Histopathology revealed an adenocarcinoma of the cecum with tumor invasion into the visceral peritoneum and metastases to the left ovary, fallopian tube, and omentum. A BRAF V600E mutation was detected.

Two months after the initial presentation, the patient started her first cycle of chemotherapy with a combination of folinic acid, fluorouracil, and oxaliplatin. She completed 11 cycles of this regimen, then was switched to capecitabine and oxaliplatin for an additional 2 cycles due to insurance concerns. At the end of treatment, there was no evidence of disease on CT, thus the patient was followed with observation. However, she presented 10 months later to the emergency department with abdominal pain, and CT revealed new lesions in the liver that were concerning for potential metastases. She started oral encorafenib 300 mg/d and intravenous cetuximab 500 mg weekly; after 1 week, encorafenib was reduced to 150 mg/d due to nausea and loss of appetite. Within 2 weeks of starting treatment, the patient reported the relatively abrupt appearance of more than 50 small papules across the shoulders and back (Figure 1A). She was referred to dermatology, and shave biopsies of 2 lesions—one from the left anterior thigh, the other from the right posterior shoulder—revealed verrucous keratosis pathology (Figure 2). At this time, encorafenib was increased again to 300 mg/d as the patient had been tolerating the reduced dose. She continued to report the appearance of new lesions for the next 3 months, after which the lesions were stable for approximately 2 months. By 2.5 months after initiation of therapy, the patient had ­undergone CT demonstrating resolution of the liver lesions. At 5 months of therapy, the patient reported a stable to slightly reduced number of skin lesions but had begun to experience worsening joint pain, and the dosage of encorafenib was reduced to 225 mg/d. At 7 months of therapy, the dosage was further reduced to 150 mg/d due to persistent arthralgia. A follow-up examination at 10 months of therapy showed improvement in the number and size of the verrucous keratoses, and near resolution was seen by 14 months after the initial onset of the lesions (Figure 1B). At 20 months after initial onset, only 1 remaining verrucous keratosis was identified on physical examination and biopsy. The patient had continued a regimen of encorafenib 150 mg/d and weekly intravenous 500 mg cetuximab up to this point. Over the entire time period that the patient was seen, up to 12 lesions located in high-friction areas had become irritated and were treated with cryotherapy, but this contributed only minorly to the patient’s overall presentation.

To the Editor:

Kratom (Mitragyna speciosa) is an evergreen tree native to Southeast Asia.¹ Its leaves contain psychoactive compounds including mitragynine and 7-­hydroxymitragynine, which exert dose-dependent effects on the central nervous system through opioid and monoaminergic receptors.^2,3 At low doses (1–5 g), kratom elicits mild stimulant effects such as increased sociability, alertness, and talkativeness. At high doses (5–15 g), kratom has depressant effects that can provide relief from pain and opioid-withdrawal symptoms.³

Traditionally, kratom has been used in Southeast Asia for recreational and ceremonial purposes, to ease opioid-withdrawal symptoms, and to reduce fatigue from manual labor.⁴ In the 21st century, availability of kratom expanded to Europe, Australia, and the United States, largely facilitated by widespread dissemination of deceitful ­marketing and unregulated sales on the internet.¹ Although large-scale epidemiologic studies evaluating kratom’s prevalence are scarce, available evidence indicates rising worldwide usage, with a notable increase in kratom-related poison center calls between 2011 and 2017 in the United States.⁵ In July 2023, kratom made headlines due to the death of a woman in Florida following use of the substance.⁶

A cross-sectional study revealed that in the United States, kratom typically is used by White individuals for self-treatment of anxiety, depression, pain, and opioid withdrawal.⁷ However, the potential for severe adverse effects and dependence on kratom can outweigh the benefits.^6,8 Reported adverse effects of kratom include tachycardia, hypercholesteremia, liver injury, hallucinations, respiratory depression, seizure, coma, and death.^9,10 We present a case of kratom-induced photodistributed hyperpigmentation.

A 63-year-old man presented to the dermatology clinic with diffuse tender, pruritic, hyperpigmented skin lesions that developed over the course of 1 year. The lesions were distributed on sun-exposed areas, including the face, neck, and forearms (Figure 1). The patient reported no other major symptoms, and his health was otherwise unremarkable. He had a medical history of psoriasiform and spongiotic dermatitis consistent with eczema, psoriasis, hypercholesteremia, and hyperlipidemia. The patient was not taking any medications at the time of presentation. He had a family history of plaque psoriasis in his father. Five years prior to the current presentation, the patient was treated with adalimumab for steroid-resistant psoriasis; however, despite initial improvement, he experienced recurrence of scaly erythematous plaques and had discontinued adalimumab the year prior to presentation.

To the Editor:

Kratom (Mitragyna speciosa) is an evergreen tree native to Southeast Asia.¹ Its leaves contain psychoactive compounds including mitragynine and 7-­hydroxymitragynine, which exert dose-dependent effects on the central nervous system through opioid and monoaminergic receptors.^2,3 At low doses (1–5 g), kratom elicits mild stimulant effects such as increased sociability, alertness, and talkativeness. At high doses (5–15 g), kratom has depressant effects that can provide relief from pain and opioid-withdrawal symptoms.³

Traditionally, kratom has been used in Southeast Asia for recreational and ceremonial purposes, to ease opioid-withdrawal symptoms, and to reduce fatigue from manual labor.⁴ In the 21st century, availability of kratom expanded to Europe, Australia, and the United States, largely facilitated by widespread dissemination of deceitful ­marketing and unregulated sales on the internet.¹ Although large-scale epidemiologic studies evaluating kratom’s prevalence are scarce, available evidence indicates rising worldwide usage, with a notable increase in kratom-related poison center calls between 2011 and 2017 in the United States.⁵ In July 2023, kratom made headlines due to the death of a woman in Florida following use of the substance.⁶

A cross-sectional study revealed that in the United States, kratom typically is used by White individuals for self-treatment of anxiety, depression, pain, and opioid withdrawal.⁷ However, the potential for severe adverse effects and dependence on kratom can outweigh the benefits.^6,8 Reported adverse effects of kratom include tachycardia, hypercholesteremia, liver injury, hallucinations, respiratory depression, seizure, coma, and death.^9,10 We present a case of kratom-induced photodistributed hyperpigmentation.

A 63-year-old man presented to the dermatology clinic with diffuse tender, pruritic, hyperpigmented skin lesions that developed over the course of 1 year. The lesions were distributed on sun-exposed areas, including the face, neck, and forearms (Figure 1). The patient reported no other major symptoms, and his health was otherwise unremarkable. He had a medical history of psoriasiform and spongiotic dermatitis consistent with eczema, psoriasis, hypercholesteremia, and hyperlipidemia. The patient was not taking any medications at the time of presentation. He had a family history of plaque psoriasis in his father. Five years prior to the current presentation, the patient was treated with adalimumab for steroid-resistant psoriasis; however, despite initial improvement, he experienced recurrence of scaly erythematous plaques and had discontinued adalimumab the year prior to presentation.

To the Editor:

Kratom (Mitragyna speciosa) is an evergreen tree native to Southeast Asia.¹ Its leaves contain psychoactive compounds including mitragynine and 7-­hydroxymitragynine, which exert dose-dependent effects on the central nervous system through opioid and monoaminergic receptors.^2,3 At low doses (1–5 g), kratom elicits mild stimulant effects such as increased sociability, alertness, and talkativeness. At high doses (5–15 g), kratom has depressant effects that can provide relief from pain and opioid-withdrawal symptoms.³

Traditionally, kratom has been used in Southeast Asia for recreational and ceremonial purposes, to ease opioid-withdrawal symptoms, and to reduce fatigue from manual labor.⁴ In the 21st century, availability of kratom expanded to Europe, Australia, and the United States, largely facilitated by widespread dissemination of deceitful ­marketing and unregulated sales on the internet.¹ Although large-scale epidemiologic studies evaluating kratom’s prevalence are scarce, available evidence indicates rising worldwide usage, with a notable increase in kratom-related poison center calls between 2011 and 2017 in the United States.⁵ In July 2023, kratom made headlines due to the death of a woman in Florida following use of the substance.⁶

A cross-sectional study revealed that in the United States, kratom typically is used by White individuals for self-treatment of anxiety, depression, pain, and opioid withdrawal.⁷ However, the potential for severe adverse effects and dependence on kratom can outweigh the benefits.^6,8 Reported adverse effects of kratom include tachycardia, hypercholesteremia, liver injury, hallucinations, respiratory depression, seizure, coma, and death.^9,10 We present a case of kratom-induced photodistributed hyperpigmentation.

A 63-year-old man presented to the dermatology clinic with diffuse tender, pruritic, hyperpigmented skin lesions that developed over the course of 1 year. The lesions were distributed on sun-exposed areas, including the face, neck, and forearms (Figure 1). The patient reported no other major symptoms, and his health was otherwise unremarkable. He had a medical history of psoriasiform and spongiotic dermatitis consistent with eczema, psoriasis, hypercholesteremia, and hyperlipidemia. The patient was not taking any medications at the time of presentation. He had a family history of plaque psoriasis in his father. Five years prior to the current presentation, the patient was treated with adalimumab for steroid-resistant psoriasis; however, despite initial improvement, he experienced recurrence of scaly erythematous plaques and had discontinued adalimumab the year prior to presentation.

To the Editor:

Pityriasis rubra pilaris (PRP) is a rare papulosquamous condition with an unknown pathogenesis and limited efficacy data, which can make treatment challenging. Some cases of PRP spontaneously resolve in a few months, which is most common in the pediatric population.¹ Pityriasis rubra pilaris in adults is likely to persist for years, and spontaneous resolution is unpredictable. Randomized clinical trials are difficult to perform due to the rarity of PRP.

Although there is no cure and no standard protocol for treating PRP, systemic retinoids historically are considered first-line therapy for moderate to severe cases.² Additional management approaches include symptomatic control with moisturizers and psychological support. Alternative systemic treatments for moderate to severe cases include methotrexate, phototherapy, and cyclosporine.²

Pityriasis rubra pilaris demonstrates a favorable response to methotrexate treatment, especially in type I cases; however, patients on this alternative therapy should be monitored for severe adverse effects (eg, hepatotoxicity, pancytopenia, pneumonitis).² Phototherapy should be approached with caution. Narrowband UVB, UVA1, and psoralen plus UVA therapy have successfully treated PRP; however, the response is variable. In some cases, the opposite effect can occur, in which the condition is photoaggravated. Phototherapy is a valid alternative form of treatment when used in combination with acitretin, and a phototest should be performed prior to starting this regimen. Cyclosporine is another immunosuppressant that can be considered for PRP treatment, though there are limited data demonstrating its efficacy.²

The introduction of biologic agents has changed the treatment approach for many dermatologic diseases, including PRP. Given the similar features between psoriasis and PRP, the biologics prescribed for psoriasis therapy also are used for patients with PRP that is challenging to treat, such as anti–tumor necrosis factor α inhibitors and IL inhibitors—specifically IL-17 and IL-23. Remission has been achieved with the use of biologics in combination with retinoid therapy.²

Biologic therapies used for PRP effectively inhibit cytokines and reduce the overall inflammatory processes involved in the development of the scaly patches and plaques seen in this condition. However, most reported clinical experiences are case studies, and more research in the form of randomized clinical trials is needed to understand the efficacy and long-term effects of this form of treatment in PRP. We present a case of a patient with refractory adult subtype I PRP that was successfully treated with the IL-23 inhibitor risankizumab.

A 65-year-old man was referred to Florida Academic Dermatology Center (Coral Gables, Florida) with biopsy-proven PRP diagnosed 1 year prior. The patient reported experiencing a debilitating quality of life in the year since diagnosis (Figure 1). Treatment attempts with dupilumab, tralokinumab, intramuscular steroid injections, and topical corticosteroids had failed (Figure 2). Following evaluation at Florida Academic Dermatology Center, the patient was started on acitretin 25 mg every other day and received an initial subcutaneous injection of ixekizumab 160 mg (an IL-17 inhibitor) followed 2 weeks later by a second injection of 80 mg. After the 2 doses of ixekizumab, the patient’s condition worsened with the development of pinpoint hemorrhagic lesions. The medication was discontinued, and he was started on risankizumab 150 mg at the approved dosing regimen for plaque psoriasis in combination with the acitretin therapy. Prior to starting risankizumab, the affected body surface area (BSA) was 80%. At 1-month follow-up, he showed improvement with reduction in scaling and erythema and an affected BSA of 30% (Figure 3). At 4-month follow-up, he continued showing improvement with an affected BSA of 10% (Figure 4). Acitretin was discontinued, and the patient has been successfully maintained on risankizumab 150 mg/mL subcutaneous injections every 12 weeks since.

To the Editor:

Pityriasis rubra pilaris (PRP) is a rare papulosquamous condition with an unknown pathogenesis and limited efficacy data, which can make treatment challenging. Some cases of PRP spontaneously resolve in a few months, which is most common in the pediatric population.¹ Pityriasis rubra pilaris in adults is likely to persist for years, and spontaneous resolution is unpredictable. Randomized clinical trials are difficult to perform due to the rarity of PRP.

Although there is no cure and no standard protocol for treating PRP, systemic retinoids historically are considered first-line therapy for moderate to severe cases.² Additional management approaches include symptomatic control with moisturizers and psychological support. Alternative systemic treatments for moderate to severe cases include methotrexate, phototherapy, and cyclosporine.²

Pityriasis rubra pilaris demonstrates a favorable response to methotrexate treatment, especially in type I cases; however, patients on this alternative therapy should be monitored for severe adverse effects (eg, hepatotoxicity, pancytopenia, pneumonitis).² Phototherapy should be approached with caution. Narrowband UVB, UVA1, and psoralen plus UVA therapy have successfully treated PRP; however, the response is variable. In some cases, the opposite effect can occur, in which the condition is photoaggravated. Phototherapy is a valid alternative form of treatment when used in combination with acitretin, and a phototest should be performed prior to starting this regimen. Cyclosporine is another immunosuppressant that can be considered for PRP treatment, though there are limited data demonstrating its efficacy.²

The introduction of biologic agents has changed the treatment approach for many dermatologic diseases, including PRP. Given the similar features between psoriasis and PRP, the biologics prescribed for psoriasis therapy also are used for patients with PRP that is challenging to treat, such as anti–tumor necrosis factor α inhibitors and IL inhibitors—specifically IL-17 and IL-23. Remission has been achieved with the use of biologics in combination with retinoid therapy.²

Biologic therapies used for PRP effectively inhibit cytokines and reduce the overall inflammatory processes involved in the development of the scaly patches and plaques seen in this condition. However, most reported clinical experiences are case studies, and more research in the form of randomized clinical trials is needed to understand the efficacy and long-term effects of this form of treatment in PRP. We present a case of a patient with refractory adult subtype I PRP that was successfully treated with the IL-23 inhibitor risankizumab.

A 65-year-old man was referred to Florida Academic Dermatology Center (Coral Gables, Florida) with biopsy-proven PRP diagnosed 1 year prior. The patient reported experiencing a debilitating quality of life in the year since diagnosis (Figure 1). Treatment attempts with dupilumab, tralokinumab, intramuscular steroid injections, and topical corticosteroids had failed (Figure 2). Following evaluation at Florida Academic Dermatology Center, the patient was started on acitretin 25 mg every other day and received an initial subcutaneous injection of ixekizumab 160 mg (an IL-17 inhibitor) followed 2 weeks later by a second injection of 80 mg. After the 2 doses of ixekizumab, the patient’s condition worsened with the development of pinpoint hemorrhagic lesions. The medication was discontinued, and he was started on risankizumab 150 mg at the approved dosing regimen for plaque psoriasis in combination with the acitretin therapy. Prior to starting risankizumab, the affected body surface area (BSA) was 80%. At 1-month follow-up, he showed improvement with reduction in scaling and erythema and an affected BSA of 30% (Figure 3). At 4-month follow-up, he continued showing improvement with an affected BSA of 10% (Figure 4). Acitretin was discontinued, and the patient has been successfully maintained on risankizumab 150 mg/mL subcutaneous injections every 12 weeks since.

To the Editor:

Pityriasis rubra pilaris (PRP) is a rare papulosquamous condition with an unknown pathogenesis and limited efficacy data, which can make treatment challenging. Some cases of PRP spontaneously resolve in a few months, which is most common in the pediatric population.¹ Pityriasis rubra pilaris in adults is likely to persist for years, and spontaneous resolution is unpredictable. Randomized clinical trials are difficult to perform due to the rarity of PRP.

Although there is no cure and no standard protocol for treating PRP, systemic retinoids historically are considered first-line therapy for moderate to severe cases.² Additional management approaches include symptomatic control with moisturizers and psychological support. Alternative systemic treatments for moderate to severe cases include methotrexate, phototherapy, and cyclosporine.²

Pityriasis rubra pilaris demonstrates a favorable response to methotrexate treatment, especially in type I cases; however, patients on this alternative therapy should be monitored for severe adverse effects (eg, hepatotoxicity, pancytopenia, pneumonitis).² Phototherapy should be approached with caution. Narrowband UVB, UVA1, and psoralen plus UVA therapy have successfully treated PRP; however, the response is variable. In some cases, the opposite effect can occur, in which the condition is photoaggravated. Phototherapy is a valid alternative form of treatment when used in combination with acitretin, and a phototest should be performed prior to starting this regimen. Cyclosporine is another immunosuppressant that can be considered for PRP treatment, though there are limited data demonstrating its efficacy.²

The introduction of biologic agents has changed the treatment approach for many dermatologic diseases, including PRP. Given the similar features between psoriasis and PRP, the biologics prescribed for psoriasis therapy also are used for patients with PRP that is challenging to treat, such as anti–tumor necrosis factor α inhibitors and IL inhibitors—specifically IL-17 and IL-23. Remission has been achieved with the use of biologics in combination with retinoid therapy.²

Biologic therapies used for PRP effectively inhibit cytokines and reduce the overall inflammatory processes involved in the development of the scaly patches and plaques seen in this condition. However, most reported clinical experiences are case studies, and more research in the form of randomized clinical trials is needed to understand the efficacy and long-term effects of this form of treatment in PRP. We present a case of a patient with refractory adult subtype I PRP that was successfully treated with the IL-23 inhibitor risankizumab.

A 65-year-old man was referred to Florida Academic Dermatology Center (Coral Gables, Florida) with biopsy-proven PRP diagnosed 1 year prior. The patient reported experiencing a debilitating quality of life in the year since diagnosis (Figure 1). Treatment attempts with dupilumab, tralokinumab, intramuscular steroid injections, and topical corticosteroids had failed (Figure 2). Following evaluation at Florida Academic Dermatology Center, the patient was started on acitretin 25 mg every other day and received an initial subcutaneous injection of ixekizumab 160 mg (an IL-17 inhibitor) followed 2 weeks later by a second injection of 80 mg. After the 2 doses of ixekizumab, the patient’s condition worsened with the development of pinpoint hemorrhagic lesions. The medication was discontinued, and he was started on risankizumab 150 mg at the approved dosing regimen for plaque psoriasis in combination with the acitretin therapy. Prior to starting risankizumab, the affected body surface area (BSA) was 80%. At 1-month follow-up, he showed improvement with reduction in scaling and erythema and an affected BSA of 30% (Figure 3). At 4-month follow-up, he continued showing improvement with an affected BSA of 10% (Figure 4). Acitretin was discontinued, and the patient has been successfully maintained on risankizumab 150 mg/mL subcutaneous injections every 12 weeks since.

To the Editor:

Chronic cutaneous lupus erythematosus (CCLE) is an inflammatory condition with myriad cutaneous manifestations. Most forms of CCLE have the potential to progress to systemic lupus erythematosus (SLE).¹

Blaschkolinear lupus erythematosus (BLE) is an exceedingly rare subtype of cutaneous lupus erythematosus that usually manifests during childhood as linear plaques along the lines of Blaschko.^2,3 Under normal conditions, Blaschko lines are not noticeable; they correspond to the direction of ectodermal cell migration during cutaneous embryogenesis.^4,5 The embryonic cells travel ventrolaterally, forming a V-shaped pattern on the back, an S-shaped pattern on the trunk, and an hourglass-shaped pattern on the face with several perpendicular intersections near the mouth and nose.⁶ During their migration, the cells are susceptible to somatic mutations and clonal expansion, resulting in a monoclonal population of genetically heterogenous cells. This phenomenon is known as somatic mosaicism and may lead to an increased susceptibility to an array of congenital and inflammatory dermatoses, such as cutaneous lupus erythematosus.⁴ Blaschkolinear entities tend to manifest in a unilateral distribution following exposure to a certain environmental trigger, such as trauma, viral illness, or UV radiation, although a trigger is not always present.⁷ We report a case of BLE manifesting on the head and neck in an adult patient.

A 46-year-old man presented with a pruritic rash of 3 months’ duration on the right cheek that extended inferiorly to the right upper chest. He had a medical history of well-controlled psoriasis, and he denied any antecedent trauma, fevers, chills, arthralgia, or night sweats. There had been no improvement with mometasone ointment 0.1% applied daily for 2 months as prescribed by his primary care provider. Physical examination revealed indurated, red-brown, atrophic plaques in a blaschkolinear distribution around the nose, right upper jaw, right side of the neck, and right upper chest (Figure, A).

To the Editor:

Chronic cutaneous lupus erythematosus (CCLE) is an inflammatory condition with myriad cutaneous manifestations. Most forms of CCLE have the potential to progress to systemic lupus erythematosus (SLE).¹

Blaschkolinear lupus erythematosus (BLE) is an exceedingly rare subtype of cutaneous lupus erythematosus that usually manifests during childhood as linear plaques along the lines of Blaschko.^2,3 Under normal conditions, Blaschko lines are not noticeable; they correspond to the direction of ectodermal cell migration during cutaneous embryogenesis.^4,5 The embryonic cells travel ventrolaterally, forming a V-shaped pattern on the back, an S-shaped pattern on the trunk, and an hourglass-shaped pattern on the face with several perpendicular intersections near the mouth and nose.⁶ During their migration, the cells are susceptible to somatic mutations and clonal expansion, resulting in a monoclonal population of genetically heterogenous cells. This phenomenon is known as somatic mosaicism and may lead to an increased susceptibility to an array of congenital and inflammatory dermatoses, such as cutaneous lupus erythematosus.⁴ Blaschkolinear entities tend to manifest in a unilateral distribution following exposure to a certain environmental trigger, such as trauma, viral illness, or UV radiation, although a trigger is not always present.⁷ We report a case of BLE manifesting on the head and neck in an adult patient.

A 46-year-old man presented with a pruritic rash of 3 months’ duration on the right cheek that extended inferiorly to the right upper chest. He had a medical history of well-controlled psoriasis, and he denied any antecedent trauma, fevers, chills, arthralgia, or night sweats. There had been no improvement with mometasone ointment 0.1% applied daily for 2 months as prescribed by his primary care provider. Physical examination revealed indurated, red-brown, atrophic plaques in a blaschkolinear distribution around the nose, right upper jaw, right side of the neck, and right upper chest (Figure, A).

To the Editor:

Chronic cutaneous lupus erythematosus (CCLE) is an inflammatory condition with myriad cutaneous manifestations. Most forms of CCLE have the potential to progress to systemic lupus erythematosus (SLE).¹

Blaschkolinear lupus erythematosus (BLE) is an exceedingly rare subtype of cutaneous lupus erythematosus that usually manifests during childhood as linear plaques along the lines of Blaschko.^2,3 Under normal conditions, Blaschko lines are not noticeable; they correspond to the direction of ectodermal cell migration during cutaneous embryogenesis.^4,5 The embryonic cells travel ventrolaterally, forming a V-shaped pattern on the back, an S-shaped pattern on the trunk, and an hourglass-shaped pattern on the face with several perpendicular intersections near the mouth and nose.⁶ During their migration, the cells are susceptible to somatic mutations and clonal expansion, resulting in a monoclonal population of genetically heterogenous cells. This phenomenon is known as somatic mosaicism and may lead to an increased susceptibility to an array of congenital and inflammatory dermatoses, such as cutaneous lupus erythematosus.⁴ Blaschkolinear entities tend to manifest in a unilateral distribution following exposure to a certain environmental trigger, such as trauma, viral illness, or UV radiation, although a trigger is not always present.⁷ We report a case of BLE manifesting on the head and neck in an adult patient.

A 46-year-old man presented with a pruritic rash of 3 months’ duration on the right cheek that extended inferiorly to the right upper chest. He had a medical history of well-controlled psoriasis, and he denied any antecedent trauma, fevers, chills, arthralgia, or night sweats. There had been no improvement with mometasone ointment 0.1% applied daily for 2 months as prescribed by his primary care provider. Physical examination revealed indurated, red-brown, atrophic plaques in a blaschkolinear distribution around the nose, right upper jaw, right side of the neck, and right upper chest (Figure, A).

To the Editor:
Crusted scabies (formerly known as Norwegian scabies) is a rare and highly contagious variant of scabies, in which the skin is infested with thousands to millions of Sarcoptes scabiei var hominis mites. We present a case of skin changes that were misdiagnosed as atopic dermatitis, seborrhea, xerosis, and drug eruption on initial presentation, which prompted treatment with a corticosteroid that inadvertently caused progression to crusted scabies.

A 79-year-old woman who uses a wheelchair presented to the clinic with skin changes that consisted of diffuse, severely pruritic, erythematous plaques on the head, neck, trunk, face, and extremities of 2 years’ duration. She had a medical history of hyperlipidemia, hypertension, and hyperglycemia, as well as a stroke that required hospitalization 2 years prior to the onset of the skin changes. She had no history of allergies.

Prior clinical diagnoses by primary care and dermatology included xerosis, atopic dermatitis, seborrhea, and drug eruption. She was treated with a mid-potency topical corticosteroid (triamcinolone acetonide cream 0.1%) twice daily and prednisone 40 mg once daily for 2- to 4-week courses over an 8-month period without reduction in symptoms.

Physical examination at the current presentation revealed golden, crusted, fine, powdery but slightly sticky flakes that spread diffusely across the entire body and came off in crumbles with a simple touch. These widespread crusts were easily visible on clothing. There was underlying diffuse erythema beneath the flaking skin on the trunk and proximal extremities. The scale and shedding skin laid in piles on the patient’s lap and resembled brown sugar (Figure 1). The patient also reported decreased hand function and dexterity due to the yellowbrown, thick, crusty plaques that had developed on both the palmar and dorsal sides of the hands (Figure 2). Erythematous plaques on the scalp, forehead, and inner ears resembled seborrhea (Figure 3). Pruritus severity was rated by the patient as 10 of 10, and she scratched her skin the entire time she was in the clinic. The patient was emotional and stated that she had not been able to sleep due to the discomfort. We suspected scabies, and the patient was reassured to learn that it could be confirmed with a simple skin scrape test.

The crusted lesions on the patient's hands were scraped with a #15-blade scalpel, and a routine potassium hydroxide mount was performed. The skin scrapings were placed on a slide with a drop of 10% potassium hydroxide and observed under low-power (×10) and high-power (×40) microscopy, which revealed thousands of mites and eggs (along with previously hatched eggs) (Figure 4) and quickly confirmed a diagnosis of crusted scabies.an extremely contagious form of scabies seen in older patients with compromised immune systems, malnutrition, or disabilities. The patient was prescribed oral ivermectin (3 mg dosed at 200 μg/kg of body weight) and topical permethrin 5%, neither of which she took, as she died of a COVID-19 infection complication 3 days after this diagnostic clinic visit.

Classic and crusted scabies are both caused by infestation of the Sarcoptes scabiei var hominis mite. Classic scabies is a result of an infestation of a small number of mites (commonly 5–15 mites), while crusted scabies is due to hyperinfestation by as many as millions of mites, the latter often requiring more aggressive treatment. The mites are first transmitted to humans by either skin-toskin contact or fomites on bedding and clothing. The scabies mite undergoes 4 life cycle stages: egg, larvae, nymph, and adult. Once female mites are transmitted, they burrow under the skin and lay 2 to 3 eggs per day. The eggs hatch within 3 to 4 days, after which the larvae migrate to the skin surface. The larval stage lasts for 3 to 4 days, during which the larvae burrow into the stratum corneum to create molting pouches, until they molt into slightly larger nymphs. Nymphs can be found in hair follicles or molting pouches until they further molt within 3 to 4 days into adults, which are round, saclike mites. The adult male and female mites then mate, leaving the female fertile for the rest of her 1- to 2-month lifespan. Impregnated female mites traverse the skin surface in search of a burrow site, using the pulvilli on the anterior aspect of 2 legs to hold onto the skin. Once burrowed, the female mite continues to lay eggs for the rest of her life, with approximately 10% of her eggs resulting in adult mites. Male mites feed in shallow pits of the skin until they find a female burrow site for mating.¹ This continuous life cycle of the scabies mite gives rise to highly transmissible, pruritic skin excoriations, as demonstrated in our patient.

The skin has a relatively late inflammatory and adaptive immune response to scabies, typically occurring 4 to 6 weeks after the initial infestation.² This delayed inflammatory response and onset of symptoms may be due to the scabies mite’s ability to alter aspects of the host’s immune response, which differs in classic vs crusted scabies. In classic scabies, there is a predominance of CD4+ T cells in the dermis and minimal CD8+ T cells. The opposite is true in crusted scabies— there is an overwhelming infiltration of CD8+ T cells and minimal CD4+ T cells.³ The CD8+ T-cell predominance in crusted scabies is hypothesized to be the cause of keratinocyte apoptosis, resulting in epidermal hyperproliferation. Keratinocyte apoptosis also secretes cytokines, which may lead to the immunologic targeting of healthy skin cells. The damage of healthy dermal cells contributes to the inability of the skin’s immune system to mount an effective response, allowing the parasite to grow uncontrollably in patients with crusted scabies.⁴

This ineffective immune response is further exacerbated by corticosteroids, which are commonly prescribed for pruritus experienced by patients with scabies infestations. The mechanism of action of corticosteroids is the production of anti-inflammatory, antimitotic, and immunosuppressive effects.⁵ Because the integumentary immune system is imbalanced during crusted scabies infestation, the immunosuppressive mechanism of oral and topical corticosteroids further reduces the cellular immune response to scabies. The flourishing of the scabies mites along with keratinocyte apoptosis⁴ results in the development of hyperkeratotic skin crusting, most frequently on the palms, soles, arms, and legs. Risk factors for crusted scabies include immunosuppression, hospitalization, crowded living conditions, and poor hygiene, though no known risk factors were documented in up to 42% (33/78) of patients with crusted scabies in one study.⁶

Patients with crusted scabies typically present with generalized, poorly defined, erythematous, fissured plaques covered by scaling and crusts. Plaques on bony prominences such as finger articulations and elbows may have a thick verrucous aspect.¹ Skin flaking that resembles brown sugar—a mixture of white sugar and molasses—is a clue to the diagnosis of crusted scabies. Brown sugar has a slightly sandy and sticky texture that ranges in color from very light brown to very dark brown. When present, flakes always appears slightly lighter than the patient’s skin tone. Although skin burrows are pathognomonic and clinically recognizable features of scabies, these burrows can be disguised by lesions, such as the hyperkeratotic plaques seen in our patient. The lesions may or may not be associated with pruritus, which may occur only at night, and bacterial superinfection has been reported in severe cases of crusted scabies,⁷ as scratching can cause sores, which may lead to infection. In severe cases, the constant scratching could lead to sepsis if the infection enters the bloodstream.⁸ Another symptom of scabies is a rash that causes small bumps that tend to form in a line, resembling small bites, hives, or pimples, and scaly plaques can lead to misdiagnosis as atopic dermatitis.

Treatment often is delayed due to misdiagnosis, as seen in our patient. Common misdiagnoses include atopic dermatitis, pityriasis rosea, systemic lupus erythematosus, bullous pemphigoid, lichen planus, pediculosis corporis, seborrheic scalp dermatitis, and adverse drug reactions.⁹ Patients with extensive infestations of crusted scabies should be treated with a 4-week course of permethrin cream 5% daily for 1 week, then twice per week until resolved, and oral ivermectin 200 μg/kg dosed 1 week apart for up to 4 weeks, if needed.¹ Topical permethrin works by producing a selective neurotoxic effect on invertebrates such as scabies mites, which disrupts the function of voltage-gated sodium channels, thereby paralyzing the adult mites to halt the spread of infestation. However, treatment with topical medications can be difficult due to the thick crusts that have formed, which make it more challenging for the skin to properly absorb the treatment. Additionally, surgical debridement as an adjunct procedure has been done to improve the effectiveness of topical medications by removing all the mites in skin.¹⁰ On the other hand, the mechanism in which ivermectin treats scabies infestations is poorly understood. Current research suggests that ivermectin works by causing persistent opening of pH-gated chloride channels in scabies mites.¹¹ There is emerging concern for drug resistance to these scabicides,¹² revealing a need for further research of treatment options.

Patients with crusted scabies can have an extremely large number of mites (up to 2 million), making them more infectious than patients with classic scabies.¹³ As a result, it is imperative to reduce environmental transmission and risk for reinfection with mites during treatment. Because crusted scabies is transmitted by prolonged skinto- skin contact or by contact with personal items of an infected person (eg, bedding, clothing), treatment guidelines require all clothing, bedding, and towels of a patient with scabies to be machine-washed and dried with hot water and hot dryer cycles. If an item cannot be washed, it should be stored in a sealed plastic bag for 1 week, as scabies mites cannot survive more than 2 to 3 days away from their host of human skin.¹³ Treatment of close contacts of patients with scabies is recommended, as well as for those in endemic areas or closed communities, such as nursing homes or jails.

To the Editor:
Crusted scabies (formerly known as Norwegian scabies) is a rare and highly contagious variant of scabies, in which the skin is infested with thousands to millions of Sarcoptes scabiei var hominis mites. We present a case of skin changes that were misdiagnosed as atopic dermatitis, seborrhea, xerosis, and drug eruption on initial presentation, which prompted treatment with a corticosteroid that inadvertently caused progression to crusted scabies.

A 79-year-old woman who uses a wheelchair presented to the clinic with skin changes that consisted of diffuse, severely pruritic, erythematous plaques on the head, neck, trunk, face, and extremities of 2 years’ duration. She had a medical history of hyperlipidemia, hypertension, and hyperglycemia, as well as a stroke that required hospitalization 2 years prior to the onset of the skin changes. She had no history of allergies.

Prior clinical diagnoses by primary care and dermatology included xerosis, atopic dermatitis, seborrhea, and drug eruption. She was treated with a mid-potency topical corticosteroid (triamcinolone acetonide cream 0.1%) twice daily and prednisone 40 mg once daily for 2- to 4-week courses over an 8-month period without reduction in symptoms.

Physical examination at the current presentation revealed golden, crusted, fine, powdery but slightly sticky flakes that spread diffusely across the entire body and came off in crumbles with a simple touch. These widespread crusts were easily visible on clothing. There was underlying diffuse erythema beneath the flaking skin on the trunk and proximal extremities. The scale and shedding skin laid in piles on the patient’s lap and resembled brown sugar (Figure 1). The patient also reported decreased hand function and dexterity due to the yellowbrown, thick, crusty plaques that had developed on both the palmar and dorsal sides of the hands (Figure 2). Erythematous plaques on the scalp, forehead, and inner ears resembled seborrhea (Figure 3). Pruritus severity was rated by the patient as 10 of 10, and she scratched her skin the entire time she was in the clinic. The patient was emotional and stated that she had not been able to sleep due to the discomfort. We suspected scabies, and the patient was reassured to learn that it could be confirmed with a simple skin scrape test.

The crusted lesions on the patient's hands were scraped with a #15-blade scalpel, and a routine potassium hydroxide mount was performed. The skin scrapings were placed on a slide with a drop of 10% potassium hydroxide and observed under low-power (×10) and high-power (×40) microscopy, which revealed thousands of mites and eggs (along with previously hatched eggs) (Figure 4) and quickly confirmed a diagnosis of crusted scabies.an extremely contagious form of scabies seen in older patients with compromised immune systems, malnutrition, or disabilities. The patient was prescribed oral ivermectin (3 mg dosed at 200 μg/kg of body weight) and topical permethrin 5%, neither of which she took, as she died of a COVID-19 infection complication 3 days after this diagnostic clinic visit.

Classic and crusted scabies are both caused by infestation of the Sarcoptes scabiei var hominis mite. Classic scabies is a result of an infestation of a small number of mites (commonly 5–15 mites), while crusted scabies is due to hyperinfestation by as many as millions of mites, the latter often requiring more aggressive treatment. The mites are first transmitted to humans by either skin-toskin contact or fomites on bedding and clothing. The scabies mite undergoes 4 life cycle stages: egg, larvae, nymph, and adult. Once female mites are transmitted, they burrow under the skin and lay 2 to 3 eggs per day. The eggs hatch within 3 to 4 days, after which the larvae migrate to the skin surface. The larval stage lasts for 3 to 4 days, during which the larvae burrow into the stratum corneum to create molting pouches, until they molt into slightly larger nymphs. Nymphs can be found in hair follicles or molting pouches until they further molt within 3 to 4 days into adults, which are round, saclike mites. The adult male and female mites then mate, leaving the female fertile for the rest of her 1- to 2-month lifespan. Impregnated female mites traverse the skin surface in search of a burrow site, using the pulvilli on the anterior aspect of 2 legs to hold onto the skin. Once burrowed, the female mite continues to lay eggs for the rest of her life, with approximately 10% of her eggs resulting in adult mites. Male mites feed in shallow pits of the skin until they find a female burrow site for mating.¹ This continuous life cycle of the scabies mite gives rise to highly transmissible, pruritic skin excoriations, as demonstrated in our patient.

The skin has a relatively late inflammatory and adaptive immune response to scabies, typically occurring 4 to 6 weeks after the initial infestation.² This delayed inflammatory response and onset of symptoms may be due to the scabies mite’s ability to alter aspects of the host’s immune response, which differs in classic vs crusted scabies. In classic scabies, there is a predominance of CD4+ T cells in the dermis and minimal CD8+ T cells. The opposite is true in crusted scabies— there is an overwhelming infiltration of CD8+ T cells and minimal CD4+ T cells.³ The CD8+ T-cell predominance in crusted scabies is hypothesized to be the cause of keratinocyte apoptosis, resulting in epidermal hyperproliferation. Keratinocyte apoptosis also secretes cytokines, which may lead to the immunologic targeting of healthy skin cells. The damage of healthy dermal cells contributes to the inability of the skin’s immune system to mount an effective response, allowing the parasite to grow uncontrollably in patients with crusted scabies.⁴

This ineffective immune response is further exacerbated by corticosteroids, which are commonly prescribed for pruritus experienced by patients with scabies infestations. The mechanism of action of corticosteroids is the production of anti-inflammatory, antimitotic, and immunosuppressive effects.⁵ Because the integumentary immune system is imbalanced during crusted scabies infestation, the immunosuppressive mechanism of oral and topical corticosteroids further reduces the cellular immune response to scabies. The flourishing of the scabies mites along with keratinocyte apoptosis⁴ results in the development of hyperkeratotic skin crusting, most frequently on the palms, soles, arms, and legs. Risk factors for crusted scabies include immunosuppression, hospitalization, crowded living conditions, and poor hygiene, though no known risk factors were documented in up to 42% (33/78) of patients with crusted scabies in one study.⁶

Patients with crusted scabies typically present with generalized, poorly defined, erythematous, fissured plaques covered by scaling and crusts. Plaques on bony prominences such as finger articulations and elbows may have a thick verrucous aspect.¹ Skin flaking that resembles brown sugar—a mixture of white sugar and molasses—is a clue to the diagnosis of crusted scabies. Brown sugar has a slightly sandy and sticky texture that ranges in color from very light brown to very dark brown. When present, flakes always appears slightly lighter than the patient’s skin tone. Although skin burrows are pathognomonic and clinically recognizable features of scabies, these burrows can be disguised by lesions, such as the hyperkeratotic plaques seen in our patient. The lesions may or may not be associated with pruritus, which may occur only at night, and bacterial superinfection has been reported in severe cases of crusted scabies,⁷ as scratching can cause sores, which may lead to infection. In severe cases, the constant scratching could lead to sepsis if the infection enters the bloodstream.⁸ Another symptom of scabies is a rash that causes small bumps that tend to form in a line, resembling small bites, hives, or pimples, and scaly plaques can lead to misdiagnosis as atopic dermatitis.

Treatment often is delayed due to misdiagnosis, as seen in our patient. Common misdiagnoses include atopic dermatitis, pityriasis rosea, systemic lupus erythematosus, bullous pemphigoid, lichen planus, pediculosis corporis, seborrheic scalp dermatitis, and adverse drug reactions.⁹ Patients with extensive infestations of crusted scabies should be treated with a 4-week course of permethrin cream 5% daily for 1 week, then twice per week until resolved, and oral ivermectin 200 μg/kg dosed 1 week apart for up to 4 weeks, if needed.¹ Topical permethrin works by producing a selective neurotoxic effect on invertebrates such as scabies mites, which disrupts the function of voltage-gated sodium channels, thereby paralyzing the adult mites to halt the spread of infestation. However, treatment with topical medications can be difficult due to the thick crusts that have formed, which make it more challenging for the skin to properly absorb the treatment. Additionally, surgical debridement as an adjunct procedure has been done to improve the effectiveness of topical medications by removing all the mites in skin.¹⁰ On the other hand, the mechanism in which ivermectin treats scabies infestations is poorly understood. Current research suggests that ivermectin works by causing persistent opening of pH-gated chloride channels in scabies mites.¹¹ There is emerging concern for drug resistance to these scabicides,¹² revealing a need for further research of treatment options.

Patients with crusted scabies can have an extremely large number of mites (up to 2 million), making them more infectious than patients with classic scabies.¹³ As a result, it is imperative to reduce environmental transmission and risk for reinfection with mites during treatment. Because crusted scabies is transmitted by prolonged skinto- skin contact or by contact with personal items of an infected person (eg, bedding, clothing), treatment guidelines require all clothing, bedding, and towels of a patient with scabies to be machine-washed and dried with hot water and hot dryer cycles. If an item cannot be washed, it should be stored in a sealed plastic bag for 1 week, as scabies mites cannot survive more than 2 to 3 days away from their host of human skin.¹³ Treatment of close contacts of patients with scabies is recommended, as well as for those in endemic areas or closed communities, such as nursing homes or jails.

To the Editor:
Crusted scabies (formerly known as Norwegian scabies) is a rare and highly contagious variant of scabies, in which the skin is infested with thousands to millions of Sarcoptes scabiei var hominis mites. We present a case of skin changes that were misdiagnosed as atopic dermatitis, seborrhea, xerosis, and drug eruption on initial presentation, which prompted treatment with a corticosteroid that inadvertently caused progression to crusted scabies.

A 79-year-old woman who uses a wheelchair presented to the clinic with skin changes that consisted of diffuse, severely pruritic, erythematous plaques on the head, neck, trunk, face, and extremities of 2 years’ duration. She had a medical history of hyperlipidemia, hypertension, and hyperglycemia, as well as a stroke that required hospitalization 2 years prior to the onset of the skin changes. She had no history of allergies.

Prior clinical diagnoses by primary care and dermatology included xerosis, atopic dermatitis, seborrhea, and drug eruption. She was treated with a mid-potency topical corticosteroid (triamcinolone acetonide cream 0.1%) twice daily and prednisone 40 mg once daily for 2- to 4-week courses over an 8-month period without reduction in symptoms.

Physical examination at the current presentation revealed golden, crusted, fine, powdery but slightly sticky flakes that spread diffusely across the entire body and came off in crumbles with a simple touch. These widespread crusts were easily visible on clothing. There was underlying diffuse erythema beneath the flaking skin on the trunk and proximal extremities. The scale and shedding skin laid in piles on the patient’s lap and resembled brown sugar (Figure 1). The patient also reported decreased hand function and dexterity due to the yellowbrown, thick, crusty plaques that had developed on both the palmar and dorsal sides of the hands (Figure 2). Erythematous plaques on the scalp, forehead, and inner ears resembled seborrhea (Figure 3). Pruritus severity was rated by the patient as 10 of 10, and she scratched her skin the entire time she was in the clinic. The patient was emotional and stated that she had not been able to sleep due to the discomfort. We suspected scabies, and the patient was reassured to learn that it could be confirmed with a simple skin scrape test.

The crusted lesions on the patient's hands were scraped with a #15-blade scalpel, and a routine potassium hydroxide mount was performed. The skin scrapings were placed on a slide with a drop of 10% potassium hydroxide and observed under low-power (×10) and high-power (×40) microscopy, which revealed thousands of mites and eggs (along with previously hatched eggs) (Figure 4) and quickly confirmed a diagnosis of crusted scabies.an extremely contagious form of scabies seen in older patients with compromised immune systems, malnutrition, or disabilities. The patient was prescribed oral ivermectin (3 mg dosed at 200 μg/kg of body weight) and topical permethrin 5%, neither of which she took, as she died of a COVID-19 infection complication 3 days after this diagnostic clinic visit.

Classic and crusted scabies are both caused by infestation of the Sarcoptes scabiei var hominis mite. Classic scabies is a result of an infestation of a small number of mites (commonly 5–15 mites), while crusted scabies is due to hyperinfestation by as many as millions of mites, the latter often requiring more aggressive treatment. The mites are first transmitted to humans by either skin-toskin contact or fomites on bedding and clothing. The scabies mite undergoes 4 life cycle stages: egg, larvae, nymph, and adult. Once female mites are transmitted, they burrow under the skin and lay 2 to 3 eggs per day. The eggs hatch within 3 to 4 days, after which the larvae migrate to the skin surface. The larval stage lasts for 3 to 4 days, during which the larvae burrow into the stratum corneum to create molting pouches, until they molt into slightly larger nymphs. Nymphs can be found in hair follicles or molting pouches until they further molt within 3 to 4 days into adults, which are round, saclike mites. The adult male and female mites then mate, leaving the female fertile for the rest of her 1- to 2-month lifespan. Impregnated female mites traverse the skin surface in search of a burrow site, using the pulvilli on the anterior aspect of 2 legs to hold onto the skin. Once burrowed, the female mite continues to lay eggs for the rest of her life, with approximately 10% of her eggs resulting in adult mites. Male mites feed in shallow pits of the skin until they find a female burrow site for mating.¹ This continuous life cycle of the scabies mite gives rise to highly transmissible, pruritic skin excoriations, as demonstrated in our patient.

The skin has a relatively late inflammatory and adaptive immune response to scabies, typically occurring 4 to 6 weeks after the initial infestation.² This delayed inflammatory response and onset of symptoms may be due to the scabies mite’s ability to alter aspects of the host’s immune response, which differs in classic vs crusted scabies. In classic scabies, there is a predominance of CD4+ T cells in the dermis and minimal CD8+ T cells. The opposite is true in crusted scabies— there is an overwhelming infiltration of CD8+ T cells and minimal CD4+ T cells.³ The CD8+ T-cell predominance in crusted scabies is hypothesized to be the cause of keratinocyte apoptosis, resulting in epidermal hyperproliferation. Keratinocyte apoptosis also secretes cytokines, which may lead to the immunologic targeting of healthy skin cells. The damage of healthy dermal cells contributes to the inability of the skin’s immune system to mount an effective response, allowing the parasite to grow uncontrollably in patients with crusted scabies.⁴

This ineffective immune response is further exacerbated by corticosteroids, which are commonly prescribed for pruritus experienced by patients with scabies infestations. The mechanism of action of corticosteroids is the production of anti-inflammatory, antimitotic, and immunosuppressive effects.⁵ Because the integumentary immune system is imbalanced during crusted scabies infestation, the immunosuppressive mechanism of oral and topical corticosteroids further reduces the cellular immune response to scabies. The flourishing of the scabies mites along with keratinocyte apoptosis⁴ results in the development of hyperkeratotic skin crusting, most frequently on the palms, soles, arms, and legs. Risk factors for crusted scabies include immunosuppression, hospitalization, crowded living conditions, and poor hygiene, though no known risk factors were documented in up to 42% (33/78) of patients with crusted scabies in one study.⁶

Patients with crusted scabies typically present with generalized, poorly defined, erythematous, fissured plaques covered by scaling and crusts. Plaques on bony prominences such as finger articulations and elbows may have a thick verrucous aspect.¹ Skin flaking that resembles brown sugar—a mixture of white sugar and molasses—is a clue to the diagnosis of crusted scabies. Brown sugar has a slightly sandy and sticky texture that ranges in color from very light brown to very dark brown. When present, flakes always appears slightly lighter than the patient’s skin tone. Although skin burrows are pathognomonic and clinically recognizable features of scabies, these burrows can be disguised by lesions, such as the hyperkeratotic plaques seen in our patient. The lesions may or may not be associated with pruritus, which may occur only at night, and bacterial superinfection has been reported in severe cases of crusted scabies,⁷ as scratching can cause sores, which may lead to infection. In severe cases, the constant scratching could lead to sepsis if the infection enters the bloodstream.⁸ Another symptom of scabies is a rash that causes small bumps that tend to form in a line, resembling small bites, hives, or pimples, and scaly plaques can lead to misdiagnosis as atopic dermatitis.

Treatment often is delayed due to misdiagnosis, as seen in our patient. Common misdiagnoses include atopic dermatitis, pityriasis rosea, systemic lupus erythematosus, bullous pemphigoid, lichen planus, pediculosis corporis, seborrheic scalp dermatitis, and adverse drug reactions.⁹ Patients with extensive infestations of crusted scabies should be treated with a 4-week course of permethrin cream 5% daily for 1 week, then twice per week until resolved, and oral ivermectin 200 μg/kg dosed 1 week apart for up to 4 weeks, if needed.¹ Topical permethrin works by producing a selective neurotoxic effect on invertebrates such as scabies mites, which disrupts the function of voltage-gated sodium channels, thereby paralyzing the adult mites to halt the spread of infestation. However, treatment with topical medications can be difficult due to the thick crusts that have formed, which make it more challenging for the skin to properly absorb the treatment. Additionally, surgical debridement as an adjunct procedure has been done to improve the effectiveness of topical medications by removing all the mites in skin.¹⁰ On the other hand, the mechanism in which ivermectin treats scabies infestations is poorly understood. Current research suggests that ivermectin works by causing persistent opening of pH-gated chloride channels in scabies mites.¹¹ There is emerging concern for drug resistance to these scabicides,¹² revealing a need for further research of treatment options.

Patients with crusted scabies can have an extremely large number of mites (up to 2 million), making them more infectious than patients with classic scabies.¹³ As a result, it is imperative to reduce environmental transmission and risk for reinfection with mites during treatment. Because crusted scabies is transmitted by prolonged skinto- skin contact or by contact with personal items of an infected person (eg, bedding, clothing), treatment guidelines require all clothing, bedding, and towels of a patient with scabies to be machine-washed and dried with hot water and hot dryer cycles. If an item cannot be washed, it should be stored in a sealed plastic bag for 1 week, as scabies mites cannot survive more than 2 to 3 days away from their host of human skin.¹³ Treatment of close contacts of patients with scabies is recommended, as well as for those in endemic areas or closed communities, such as nursing homes or jails.