The Clinical Picture

A 66-year-old man presented with burning pain and erythema over the left axilla, and pustules that had ruptured and crusted over. The rash also involved the right axilla, trunk, abdomen, and face.

He said the symptoms had developed 3 days after starting to use ciprofloxacin eye drops for eye redness and purulent discharge that had been diagnosed as bacterial conjunctivitis. He was taking no other new medications. He was afebrile.

He was admitted to the hospital. Examination revealed a desquamating rash over the left axilla (Figure 1), with multiple ruptured and crusted-over pustules over the right axilla, chest, and abdomen (Figure 2). No mucosal lesions were noted. Laboratory testing showed a white blood cell count of 9.24 × 10⁹/L (reference range 4.5–11.0) with 7.8% eosinophils (0%–4%). Blood cultures were negative.

Skin biopsy study on the day after admission showed diffuse spongiosis with scattered eosinophils and a pustule beneath the stratum corneum. These findings, along with the timing and presentation of symptoms, confirmed suspicion of acute generalized exanthematous pustulosis related to the use of the eye drops.

The ciprofloxacin drops were stopped. The skin lesions were treated with emollients, topical steroids, and topical mupirocin. Improvement was noted 3 days into the hospitalization, as the lesions started to crust over and dry up and no new lesions were forming. The conjunctivitis improved with topical bacitracin ointment and prednisolone drops.

ACUTE GENERALIZED EXANTHEMATOUS PUSTULOSIS

The differential diagnosis of drug-related acute generalized exanthematous pustulosis includes Stevens-Johnson syndrome, pustular psoriasis, folliculitis, and varicella infection. The characteristic features of the rash and lesions and the temporal relationship between the start of ciprofloxacin eye drops and the development of symptoms, combined with rapid resolution of symptoms within days after discontinuing the drops, accompanied by skin biopsy study showing diffuse spongiosis with scattered eosinophils and a subcorneal pustule, confirmed the diagnosis of AGEP.

Key features of AGEP include numerous small, sterile, nonfollicular pustules on an erythematous background with associated fever and sometimes neutrophilia and eosinophilia.¹ It usually begins on the face or in the intertriginous areas and then spreads to the trunk and lower limbs with rare mucosal involvement.¹ It can be associated with viral infections, but most reported cases are related to drug reactions.²

Our patient’s case was unusual because AGEP triggered by topical medications is rarely reported, especially with ophthalmic medications.³ Drugs most commonly implicated are antibiotics including penicillins, sulfonamides, and quinolones, but other drugs such as terbinafine, diltiazem, and hydroxychloroquine have also been associated.²

AGEP may present with extensive skin desquamation, as in our patient, sometimes with bullae formation and skin sloughing manifesting as AGEP with overlapping toxic epidermal necrolysis.⁴

Diagnosis entails a careful review of medications, attention to lesion morphology, compatible disease course, and a high index of suspicion. Treatment is supportive and consists of stopping the offending agent, wound care, and antipyretics. Evidence for the use of steroids is weak.⁵

TAKE-HOME POINTS

AGEP should be considered in sudden-onset pustular desquamating erythematous rash related to use of a new medication. It is important to be aware that topical and ophthalmic medications are possible triggers. A thorough medication review should be done. Antibiotics are the most commonly implicated medications. An alternative medication should be tried. Treatment is supportive, as the condition is usually self-limiting once the offending medication is discontinued. Rarely, extensive desquamation and bullae formation may occur, which may be a manifestation of overlap features with toxic epidermal necrolysis.

A 66-year-old man presented with burning pain and erythema over the left axilla, and pustules that had ruptured and crusted over. The rash also involved the right axilla, trunk, abdomen, and face.

He said the symptoms had developed 3 days after starting to use ciprofloxacin eye drops for eye redness and purulent discharge that had been diagnosed as bacterial conjunctivitis. He was taking no other new medications. He was afebrile.

He was admitted to the hospital. Examination revealed a desquamating rash over the left axilla (Figure 1), with multiple ruptured and crusted-over pustules over the right axilla, chest, and abdomen (Figure 2). No mucosal lesions were noted. Laboratory testing showed a white blood cell count of 9.24 × 10⁹/L (reference range 4.5–11.0) with 7.8% eosinophils (0%–4%). Blood cultures were negative.

Skin biopsy study on the day after admission showed diffuse spongiosis with scattered eosinophils and a pustule beneath the stratum corneum. These findings, along with the timing and presentation of symptoms, confirmed suspicion of acute generalized exanthematous pustulosis related to the use of the eye drops.

The ciprofloxacin drops were stopped. The skin lesions were treated with emollients, topical steroids, and topical mupirocin. Improvement was noted 3 days into the hospitalization, as the lesions started to crust over and dry up and no new lesions were forming. The conjunctivitis improved with topical bacitracin ointment and prednisolone drops.

ACUTE GENERALIZED EXANTHEMATOUS PUSTULOSIS

The differential diagnosis of drug-related acute generalized exanthematous pustulosis includes Stevens-Johnson syndrome, pustular psoriasis, folliculitis, and varicella infection. The characteristic features of the rash and lesions and the temporal relationship between the start of ciprofloxacin eye drops and the development of symptoms, combined with rapid resolution of symptoms within days after discontinuing the drops, accompanied by skin biopsy study showing diffuse spongiosis with scattered eosinophils and a subcorneal pustule, confirmed the diagnosis of AGEP.

Key features of AGEP include numerous small, sterile, nonfollicular pustules on an erythematous background with associated fever and sometimes neutrophilia and eosinophilia.¹ It usually begins on the face or in the intertriginous areas and then spreads to the trunk and lower limbs with rare mucosal involvement.¹ It can be associated with viral infections, but most reported cases are related to drug reactions.²

Our patient’s case was unusual because AGEP triggered by topical medications is rarely reported, especially with ophthalmic medications.³ Drugs most commonly implicated are antibiotics including penicillins, sulfonamides, and quinolones, but other drugs such as terbinafine, diltiazem, and hydroxychloroquine have also been associated.²

AGEP may present with extensive skin desquamation, as in our patient, sometimes with bullae formation and skin sloughing manifesting as AGEP with overlapping toxic epidermal necrolysis.⁴

Diagnosis entails a careful review of medications, attention to lesion morphology, compatible disease course, and a high index of suspicion. Treatment is supportive and consists of stopping the offending agent, wound care, and antipyretics. Evidence for the use of steroids is weak.⁵

TAKE-HOME POINTS

AGEP should be considered in sudden-onset pustular desquamating erythematous rash related to use of a new medication. It is important to be aware that topical and ophthalmic medications are possible triggers. A thorough medication review should be done. Antibiotics are the most commonly implicated medications. An alternative medication should be tried. Treatment is supportive, as the condition is usually self-limiting once the offending medication is discontinued. Rarely, extensive desquamation and bullae formation may occur, which may be a manifestation of overlap features with toxic epidermal necrolysis.

A 66-year-old man presented with burning pain and erythema over the left axilla, and pustules that had ruptured and crusted over. The rash also involved the right axilla, trunk, abdomen, and face.

He said the symptoms had developed 3 days after starting to use ciprofloxacin eye drops for eye redness and purulent discharge that had been diagnosed as bacterial conjunctivitis. He was taking no other new medications. He was afebrile.

He was admitted to the hospital. Examination revealed a desquamating rash over the left axilla (Figure 1), with multiple ruptured and crusted-over pustules over the right axilla, chest, and abdomen (Figure 2). No mucosal lesions were noted. Laboratory testing showed a white blood cell count of 9.24 × 10⁹/L (reference range 4.5–11.0) with 7.8% eosinophils (0%–4%). Blood cultures were negative.

Skin biopsy study on the day after admission showed diffuse spongiosis with scattered eosinophils and a pustule beneath the stratum corneum. These findings, along with the timing and presentation of symptoms, confirmed suspicion of acute generalized exanthematous pustulosis related to the use of the eye drops.

The ciprofloxacin drops were stopped. The skin lesions were treated with emollients, topical steroids, and topical mupirocin. Improvement was noted 3 days into the hospitalization, as the lesions started to crust over and dry up and no new lesions were forming. The conjunctivitis improved with topical bacitracin ointment and prednisolone drops.

ACUTE GENERALIZED EXANTHEMATOUS PUSTULOSIS

The differential diagnosis of drug-related acute generalized exanthematous pustulosis includes Stevens-Johnson syndrome, pustular psoriasis, folliculitis, and varicella infection. The characteristic features of the rash and lesions and the temporal relationship between the start of ciprofloxacin eye drops and the development of symptoms, combined with rapid resolution of symptoms within days after discontinuing the drops, accompanied by skin biopsy study showing diffuse spongiosis with scattered eosinophils and a subcorneal pustule, confirmed the diagnosis of AGEP.

Key features of AGEP include numerous small, sterile, nonfollicular pustules on an erythematous background with associated fever and sometimes neutrophilia and eosinophilia.¹ It usually begins on the face or in the intertriginous areas and then spreads to the trunk and lower limbs with rare mucosal involvement.¹ It can be associated with viral infections, but most reported cases are related to drug reactions.²

Our patient’s case was unusual because AGEP triggered by topical medications is rarely reported, especially with ophthalmic medications.³ Drugs most commonly implicated are antibiotics including penicillins, sulfonamides, and quinolones, but other drugs such as terbinafine, diltiazem, and hydroxychloroquine have also been associated.²

AGEP may present with extensive skin desquamation, as in our patient, sometimes with bullae formation and skin sloughing manifesting as AGEP with overlapping toxic epidermal necrolysis.⁴

Diagnosis entails a careful review of medications, attention to lesion morphology, compatible disease course, and a high index of suspicion. Treatment is supportive and consists of stopping the offending agent, wound care, and antipyretics. Evidence for the use of steroids is weak.⁵

TAKE-HOME POINTS

AGEP should be considered in sudden-onset pustular desquamating erythematous rash related to use of a new medication. It is important to be aware that topical and ophthalmic medications are possible triggers. A thorough medication review should be done. Antibiotics are the most commonly implicated medications. An alternative medication should be tried. Treatment is supportive, as the condition is usually self-limiting once the offending medication is discontinued. Rarely, extensive desquamation and bullae formation may occur, which may be a manifestation of overlap features with toxic epidermal necrolysis.

A 43-year-old man presented with a 3-week history of halitosis. He was also concerned about the irregular appearance of his tongue, which he had noticed over the past 3 years. He had no history of wearing dentures or of any skin disorder.

On examination, he had poor oral hygiene and deep fissures on his tongue (Figure 1). A diagnosis of fissured tongue was made, and the patient was prescribed oral chlorhexidine gargles 3 times a day for 1 week. He was reassured of the benign nature of the condition and was educated about the need for good oral hygiene.

A BROAD DIFFERENTIAL DIAGNOSIS

Fissured tongue (scrotal tongue, plicated tongue, lingua plicata) is a common normal variant of the tongue surface with a male preponderance and a reported prevalence of 10% to 20% in the general population, and the incidence increases strikingly with age.¹

The cause is not known, but familial clustering is seen, and a polygenic or autosomal dominant hereditary component is presumed.¹

The condition may be associated with removable dentures, geographic tongue, pernicious anemia, Sjögren syndrome, psoriasis, acromegaly, macroglossia, oral-facial-digital syndrome type I, Pierre Robin syndrome, Down syndrome, and Melkersson Rosenthal syndrome.² It is usually asymptomatic, but if the fissures are deep, food may become lodged in them, resulting in tongue inflammation, burning sensation, and halitosis.¹

Typically, fissures of varying depth extending to the margin are apparent on the dorsal surface of the tongue. The condition is confined to the anterior two-thirds of the tongue, which is of ectodermal origin. Histologically, the epithelium, lamina propria, and musculature are all involved in the formation of the fissures.³ The deeper fissures may lack filliform papillae due to bacterial inflammation.³ The diagnosis is clinical, and treatment includes reassurance, advice on good oral hygiene, and tongue cleansing.¹

A 43-year-old man presented with a 3-week history of halitosis. He was also concerned about the irregular appearance of his tongue, which he had noticed over the past 3 years. He had no history of wearing dentures or of any skin disorder.

On examination, he had poor oral hygiene and deep fissures on his tongue (Figure 1). A diagnosis of fissured tongue was made, and the patient was prescribed oral chlorhexidine gargles 3 times a day for 1 week. He was reassured of the benign nature of the condition and was educated about the need for good oral hygiene.

A BROAD DIFFERENTIAL DIAGNOSIS

Fissured tongue (scrotal tongue, plicated tongue, lingua plicata) is a common normal variant of the tongue surface with a male preponderance and a reported prevalence of 10% to 20% in the general population, and the incidence increases strikingly with age.¹

The cause is not known, but familial clustering is seen, and a polygenic or autosomal dominant hereditary component is presumed.¹

The condition may be associated with removable dentures, geographic tongue, pernicious anemia, Sjögren syndrome, psoriasis, acromegaly, macroglossia, oral-facial-digital syndrome type I, Pierre Robin syndrome, Down syndrome, and Melkersson Rosenthal syndrome.² It is usually asymptomatic, but if the fissures are deep, food may become lodged in them, resulting in tongue inflammation, burning sensation, and halitosis.¹

Typically, fissures of varying depth extending to the margin are apparent on the dorsal surface of the tongue. The condition is confined to the anterior two-thirds of the tongue, which is of ectodermal origin. Histologically, the epithelium, lamina propria, and musculature are all involved in the formation of the fissures.³ The deeper fissures may lack filliform papillae due to bacterial inflammation.³ The diagnosis is clinical, and treatment includes reassurance, advice on good oral hygiene, and tongue cleansing.¹

A 43-year-old man presented with a 3-week history of halitosis. He was also concerned about the irregular appearance of his tongue, which he had noticed over the past 3 years. He had no history of wearing dentures or of any skin disorder.

On examination, he had poor oral hygiene and deep fissures on his tongue (Figure 1). A diagnosis of fissured tongue was made, and the patient was prescribed oral chlorhexidine gargles 3 times a day for 1 week. He was reassured of the benign nature of the condition and was educated about the need for good oral hygiene.

A BROAD DIFFERENTIAL DIAGNOSIS

Fissured tongue (scrotal tongue, plicated tongue, lingua plicata) is a common normal variant of the tongue surface with a male preponderance and a reported prevalence of 10% to 20% in the general population, and the incidence increases strikingly with age.¹

The cause is not known, but familial clustering is seen, and a polygenic or autosomal dominant hereditary component is presumed.¹

The condition may be associated with removable dentures, geographic tongue, pernicious anemia, Sjögren syndrome, psoriasis, acromegaly, macroglossia, oral-facial-digital syndrome type I, Pierre Robin syndrome, Down syndrome, and Melkersson Rosenthal syndrome.² It is usually asymptomatic, but if the fissures are deep, food may become lodged in them, resulting in tongue inflammation, burning sensation, and halitosis.¹

Typically, fissures of varying depth extending to the margin are apparent on the dorsal surface of the tongue. The condition is confined to the anterior two-thirds of the tongue, which is of ectodermal origin. Histologically, the epithelium, lamina propria, and musculature are all involved in the formation of the fissures.³ The deeper fissures may lack filliform papillae due to bacterial inflammation.³ The diagnosis is clinical, and treatment includes reassurance, advice on good oral hygiene, and tongue cleansing.¹

A 50-year-old man with acute myeloid leukemia (AML) with a complex karyotype was admitted to the hospital with several days of dull, left-sided abdominal pain. His most recent bone marrow biopsy showed 30% blasts, and immunophenotyping was suggestive of persistent AML (CD13+, CD34+, CD117+, CD33+, CD7+, MPO–). He was on treatment with venetoclax and cytarabine after induction therapy had failed.

On admission, his heart rate was 101 beats per minute and his blood pressure was 122/85 mm Hg. Abdominal examination revealed mild distention, hepatomegaly, and previously known massive splenomegaly, with the splenic tip extending to the umbilicus, and mild tenderness.

Results of laboratory testing revealed persistent pancytopenia:

• Hemoglobin level 6.8 g/dL (reference range 13.0–17.0)
• Total white blood cell count 0.8 × 10⁹/L (4.5–11.0)
• Platelet count 8 × 10⁹/L (150–400).

Computed tomography (CT) of the abdomen (Figure 1) showed splenomegaly (the spleen measured 26 cm, unchanged from before), but without evidence of infarct or other acute abnormality.

The next day, he developed severe, acute-onset left-sided abdominal pain. A check of vital signs showed worsening sinus tachycardia at 132 beats per minute and a drop in blood pressure to 90/56 mm Hg. He had worsening diffuse abdominal tenderness with sluggish bowel sounds. His hemoglobin concentration was 6.4 g/dL and platelet count 12 × 10⁹/L.

Urgent CT of the abdomen with contrast (Figure 2) showed heterogeneous splenic enhancement suggestive of intrasplenic hemorrhage, irregularity of the margins suggestive of rupture, and moderate hemoperitoneum.

He received supportive transfusions of blood products. Surgical exploration was deemed risky, given his overall condition and severe thrombocytopenia. Splenic angiography showed no evidence of pseudoaneurysm or focal contrast extravasation. He underwent empiric embolization of the midsplenic artery, after which his hemodynamic status stabilized. He died 4 weeks later of acute respiratory failure from pneumonia.

SPLENIC RUPTURE IN AML

Atraumatic splenic rupture is rare but potentially life-threatening, especially if the diagnosis is delayed. Conditions that can cause splenomegaly and predispose to rupture include infection (infectious mononucleosis, malaria), malignant hematologic disorders (leukemia, lymphoma), other neoplasms, and amyloidosis.¹

The literature includes a few reports of splenic rupture in patients with AML.^2–4 The proposed mechanisms include bleeding from infarction sites or tumor foci, dysregulated hemostasis, and leukostasis.

The classic presentation of splenic rupture is acute-onset left-sided abdominal pain associated with hypotension and decreasing hemoglobin levels. CT of the abdomen is confirmatory, and resuscitation with crystalloids and blood products is a vital initial step in management. Choice of treatment depends on the patient’s surgical risk and hemodynamic status; options include conservative medical management, splenic artery embolization, and exploratory laparotomy.

In patients with AML and splenomegaly presenting with acute abdominal pain, clinicians need to be aware of this potential hematologic emergency.

A 50-year-old man with acute myeloid leukemia (AML) with a complex karyotype was admitted to the hospital with several days of dull, left-sided abdominal pain. His most recent bone marrow biopsy showed 30% blasts, and immunophenotyping was suggestive of persistent AML (CD13+, CD34+, CD117+, CD33+, CD7+, MPO–). He was on treatment with venetoclax and cytarabine after induction therapy had failed.

On admission, his heart rate was 101 beats per minute and his blood pressure was 122/85 mm Hg. Abdominal examination revealed mild distention, hepatomegaly, and previously known massive splenomegaly, with the splenic tip extending to the umbilicus, and mild tenderness.

Results of laboratory testing revealed persistent pancytopenia:

• Hemoglobin level 6.8 g/dL (reference range 13.0–17.0)
• Total white blood cell count 0.8 × 10⁹/L (4.5–11.0)
• Platelet count 8 × 10⁹/L (150–400).

Computed tomography (CT) of the abdomen (Figure 1) showed splenomegaly (the spleen measured 26 cm, unchanged from before), but without evidence of infarct or other acute abnormality.

The next day, he developed severe, acute-onset left-sided abdominal pain. A check of vital signs showed worsening sinus tachycardia at 132 beats per minute and a drop in blood pressure to 90/56 mm Hg. He had worsening diffuse abdominal tenderness with sluggish bowel sounds. His hemoglobin concentration was 6.4 g/dL and platelet count 12 × 10⁹/L.

Urgent CT of the abdomen with contrast (Figure 2) showed heterogeneous splenic enhancement suggestive of intrasplenic hemorrhage, irregularity of the margins suggestive of rupture, and moderate hemoperitoneum.

He received supportive transfusions of blood products. Surgical exploration was deemed risky, given his overall condition and severe thrombocytopenia. Splenic angiography showed no evidence of pseudoaneurysm or focal contrast extravasation. He underwent empiric embolization of the midsplenic artery, after which his hemodynamic status stabilized. He died 4 weeks later of acute respiratory failure from pneumonia.

SPLENIC RUPTURE IN AML

Atraumatic splenic rupture is rare but potentially life-threatening, especially if the diagnosis is delayed. Conditions that can cause splenomegaly and predispose to rupture include infection (infectious mononucleosis, malaria), malignant hematologic disorders (leukemia, lymphoma), other neoplasms, and amyloidosis.¹

The literature includes a few reports of splenic rupture in patients with AML.^2–4 The proposed mechanisms include bleeding from infarction sites or tumor foci, dysregulated hemostasis, and leukostasis.

The classic presentation of splenic rupture is acute-onset left-sided abdominal pain associated with hypotension and decreasing hemoglobin levels. CT of the abdomen is confirmatory, and resuscitation with crystalloids and blood products is a vital initial step in management. Choice of treatment depends on the patient’s surgical risk and hemodynamic status; options include conservative medical management, splenic artery embolization, and exploratory laparotomy.

In patients with AML and splenomegaly presenting with acute abdominal pain, clinicians need to be aware of this potential hematologic emergency.

A 50-year-old man with acute myeloid leukemia (AML) with a complex karyotype was admitted to the hospital with several days of dull, left-sided abdominal pain. His most recent bone marrow biopsy showed 30% blasts, and immunophenotyping was suggestive of persistent AML (CD13+, CD34+, CD117+, CD33+, CD7+, MPO–). He was on treatment with venetoclax and cytarabine after induction therapy had failed.

On admission, his heart rate was 101 beats per minute and his blood pressure was 122/85 mm Hg. Abdominal examination revealed mild distention, hepatomegaly, and previously known massive splenomegaly, with the splenic tip extending to the umbilicus, and mild tenderness.

Results of laboratory testing revealed persistent pancytopenia:

• Hemoglobin level 6.8 g/dL (reference range 13.0–17.0)
• Total white blood cell count 0.8 × 10⁹/L (4.5–11.0)
• Platelet count 8 × 10⁹/L (150–400).

Computed tomography (CT) of the abdomen (Figure 1) showed splenomegaly (the spleen measured 26 cm, unchanged from before), but without evidence of infarct or other acute abnormality.

The next day, he developed severe, acute-onset left-sided abdominal pain. A check of vital signs showed worsening sinus tachycardia at 132 beats per minute and a drop in blood pressure to 90/56 mm Hg. He had worsening diffuse abdominal tenderness with sluggish bowel sounds. His hemoglobin concentration was 6.4 g/dL and platelet count 12 × 10⁹/L.

Urgent CT of the abdomen with contrast (Figure 2) showed heterogeneous splenic enhancement suggestive of intrasplenic hemorrhage, irregularity of the margins suggestive of rupture, and moderate hemoperitoneum.

He received supportive transfusions of blood products. Surgical exploration was deemed risky, given his overall condition and severe thrombocytopenia. Splenic angiography showed no evidence of pseudoaneurysm or focal contrast extravasation. He underwent empiric embolization of the midsplenic artery, after which his hemodynamic status stabilized. He died 4 weeks later of acute respiratory failure from pneumonia.

SPLENIC RUPTURE IN AML

Atraumatic splenic rupture is rare but potentially life-threatening, especially if the diagnosis is delayed. Conditions that can cause splenomegaly and predispose to rupture include infection (infectious mononucleosis, malaria), malignant hematologic disorders (leukemia, lymphoma), other neoplasms, and amyloidosis.¹

The literature includes a few reports of splenic rupture in patients with AML.^2–4 The proposed mechanisms include bleeding from infarction sites or tumor foci, dysregulated hemostasis, and leukostasis.

The classic presentation of splenic rupture is acute-onset left-sided abdominal pain associated with hypotension and decreasing hemoglobin levels. CT of the abdomen is confirmatory, and resuscitation with crystalloids and blood products is a vital initial step in management. Choice of treatment depends on the patient’s surgical risk and hemodynamic status; options include conservative medical management, splenic artery embolization, and exploratory laparotomy.

In patients with AML and splenomegaly presenting with acute abdominal pain, clinicians need to be aware of this potential hematologic emergency.

A 37-year-old woman presented with recurring painful swelling and erythema of the vulva over the last year. Despite a series of negative vaginal cultures, she was prescribed multiple courses of antifungal and antibacterial treatments, while her symptoms continued to worsen. She had no other relevant medical history except for occasional diarrhea and abdominal cramping, which were attributed to irritable bowel syndrome.

On examination, she had symmetric edema and erythema of the vulva (Figure 1). Closer inspection revealed a nonulcerated, slightly friable nodule of approximately 4 mm on her right labium minus. A biopsy of this region demonstrated multiple noncaseating granulomas and mixed inflammatory infiltrates. An acid-fast stain for mycobacteria was negative. Vulvar skin ultrasonography demonstrated fistulas and increased dermal thickness with altered subcutaneous tissue. She was encouraged to undergo colonoscopy, which showed findings suggestive of Crohn disease.

CROHN DISEASE OUTSIDE THE GASTROINTESTINAL TRACT

Crohn disease primarily affects the gastrointestinal tract but is associated with extraintestinal manifestations (in the oral cavity, eyes, skin, and joints) in up to 45% of patients.¹

The most common mucocutaneous manifestations are granulomatous lesions that extend directly from the gastrointestinal tract, including perianal and peristomal skin tags, fistulas, and perineal ulcerations. In most cases, the onset of cutaneous manifestations follows intestinal disease, but vulvar Crohn disease may precede gastrointestinal symptoms in approximately 25% of patients, with the average age at onset in the mid-30s.¹

The pathogenesis of vulvar Crohn disease remains unclear. One theory involves production of immune complexes from the gastrointestinal tract and a possible T-lymphocyte-mediated type IV hypersensitivity reaction.²

The most commonly reported symptoms include pain, dyspareunia, pruritus, and discharge.¹ The classic findings, found in 50% of cases, include perianal and peristomal skin tags, fistulae, perineal ulcers, linear ulcers (resembling knife cuts), abscesses, and fissures.³Figure 2 shows a linear ulcer in the gluteal cleft, with sharply demarcated borders and resembling a knife cut, in another patient treated at our institution. Associated perianal fissures are also seen, in addition to vulvar edema.⁴

The diagnosis of vulvar Crohn disease should be considered in a patient who has vulvar pain, edema, and ulcerations not otherwise explained, whether or not gastrointestinal Crohn disease is present. The diagnosis is established with clinical history and characteristic histopathology on biopsy. Multiple biopsies may be needed, and early endoscopy is recommended to establish the diagnosis. The histologic features include noncaseating and nonnecrotizing granulomatous dermatitis or vulvitis with occasional reports of eosinophilic infiltrates and necrobiosis.^5,6 An imaging study such as ultrasonography is sometimes used to differentiate between a specific cutaneous manifestation of Crohn disease and its complications such as perianal fistula or abscess.

Clinical vulvar lesions are nonspecific, and those of Crohn disease are frequently mistaken for infectious, inflammatory, or traumatic vulvitis. Diagnostic biopsy for histologic analysis is warranted.

A 37-year-old woman presented with recurring painful swelling and erythema of the vulva over the last year. Despite a series of negative vaginal cultures, she was prescribed multiple courses of antifungal and antibacterial treatments, while her symptoms continued to worsen. She had no other relevant medical history except for occasional diarrhea and abdominal cramping, which were attributed to irritable bowel syndrome.

On examination, she had symmetric edema and erythema of the vulva (Figure 1). Closer inspection revealed a nonulcerated, slightly friable nodule of approximately 4 mm on her right labium minus. A biopsy of this region demonstrated multiple noncaseating granulomas and mixed inflammatory infiltrates. An acid-fast stain for mycobacteria was negative. Vulvar skin ultrasonography demonstrated fistulas and increased dermal thickness with altered subcutaneous tissue. She was encouraged to undergo colonoscopy, which showed findings suggestive of Crohn disease.

CROHN DISEASE OUTSIDE THE GASTROINTESTINAL TRACT

Crohn disease primarily affects the gastrointestinal tract but is associated with extraintestinal manifestations (in the oral cavity, eyes, skin, and joints) in up to 45% of patients.¹

The most common mucocutaneous manifestations are granulomatous lesions that extend directly from the gastrointestinal tract, including perianal and peristomal skin tags, fistulas, and perineal ulcerations. In most cases, the onset of cutaneous manifestations follows intestinal disease, but vulvar Crohn disease may precede gastrointestinal symptoms in approximately 25% of patients, with the average age at onset in the mid-30s.¹

The pathogenesis of vulvar Crohn disease remains unclear. One theory involves production of immune complexes from the gastrointestinal tract and a possible T-lymphocyte-mediated type IV hypersensitivity reaction.²

The most commonly reported symptoms include pain, dyspareunia, pruritus, and discharge.¹ The classic findings, found in 50% of cases, include perianal and peristomal skin tags, fistulae, perineal ulcers, linear ulcers (resembling knife cuts), abscesses, and fissures.³Figure 2 shows a linear ulcer in the gluteal cleft, with sharply demarcated borders and resembling a knife cut, in another patient treated at our institution. Associated perianal fissures are also seen, in addition to vulvar edema.⁴

The diagnosis of vulvar Crohn disease should be considered in a patient who has vulvar pain, edema, and ulcerations not otherwise explained, whether or not gastrointestinal Crohn disease is present. The diagnosis is established with clinical history and characteristic histopathology on biopsy. Multiple biopsies may be needed, and early endoscopy is recommended to establish the diagnosis. The histologic features include noncaseating and nonnecrotizing granulomatous dermatitis or vulvitis with occasional reports of eosinophilic infiltrates and necrobiosis.^5,6 An imaging study such as ultrasonography is sometimes used to differentiate between a specific cutaneous manifestation of Crohn disease and its complications such as perianal fistula or abscess.

Clinical vulvar lesions are nonspecific, and those of Crohn disease are frequently mistaken for infectious, inflammatory, or traumatic vulvitis. Diagnostic biopsy for histologic analysis is warranted.

A 37-year-old woman presented with recurring painful swelling and erythema of the vulva over the last year. Despite a series of negative vaginal cultures, she was prescribed multiple courses of antifungal and antibacterial treatments, while her symptoms continued to worsen. She had no other relevant medical history except for occasional diarrhea and abdominal cramping, which were attributed to irritable bowel syndrome.

On examination, she had symmetric edema and erythema of the vulva (Figure 1). Closer inspection revealed a nonulcerated, slightly friable nodule of approximately 4 mm on her right labium minus. A biopsy of this region demonstrated multiple noncaseating granulomas and mixed inflammatory infiltrates. An acid-fast stain for mycobacteria was negative. Vulvar skin ultrasonography demonstrated fistulas and increased dermal thickness with altered subcutaneous tissue. She was encouraged to undergo colonoscopy, which showed findings suggestive of Crohn disease.

CROHN DISEASE OUTSIDE THE GASTROINTESTINAL TRACT

Crohn disease primarily affects the gastrointestinal tract but is associated with extraintestinal manifestations (in the oral cavity, eyes, skin, and joints) in up to 45% of patients.¹

The most common mucocutaneous manifestations are granulomatous lesions that extend directly from the gastrointestinal tract, including perianal and peristomal skin tags, fistulas, and perineal ulcerations. In most cases, the onset of cutaneous manifestations follows intestinal disease, but vulvar Crohn disease may precede gastrointestinal symptoms in approximately 25% of patients, with the average age at onset in the mid-30s.¹

The pathogenesis of vulvar Crohn disease remains unclear. One theory involves production of immune complexes from the gastrointestinal tract and a possible T-lymphocyte-mediated type IV hypersensitivity reaction.²

The most commonly reported symptoms include pain, dyspareunia, pruritus, and discharge.¹ The classic findings, found in 50% of cases, include perianal and peristomal skin tags, fistulae, perineal ulcers, linear ulcers (resembling knife cuts), abscesses, and fissures.³Figure 2 shows a linear ulcer in the gluteal cleft, with sharply demarcated borders and resembling a knife cut, in another patient treated at our institution. Associated perianal fissures are also seen, in addition to vulvar edema.⁴

The diagnosis of vulvar Crohn disease should be considered in a patient who has vulvar pain, edema, and ulcerations not otherwise explained, whether or not gastrointestinal Crohn disease is present. The diagnosis is established with clinical history and characteristic histopathology on biopsy. Multiple biopsies may be needed, and early endoscopy is recommended to establish the diagnosis. The histologic features include noncaseating and nonnecrotizing granulomatous dermatitis or vulvitis with occasional reports of eosinophilic infiltrates and necrobiosis.^5,6 An imaging study such as ultrasonography is sometimes used to differentiate between a specific cutaneous manifestation of Crohn disease and its complications such as perianal fistula or abscess.

Clinical vulvar lesions are nonspecific, and those of Crohn disease are frequently mistaken for infectious, inflammatory, or traumatic vulvitis. Diagnostic biopsy for histologic analysis is warranted.

A 78-year-old woman presented to the emergency department with shortness of breath and palpitations and was found to have atrial fibrillation with rapid ventricular response. Medical therapy with drug therapy and cardioversion proved ineffective. She then underwent atrioventricular node ablation and placement of a pacemaker.

At the time of admission, anticoagulation was started with full-dose enoxaparin, injected subcutaneously on the left side of the abdominal wall, as her CHA₂DS₂-VASc score (http://chadvasc.org) was 5, due to age, female sex, and history of heart failure and hypertension.

Four days after admission, she reported lower abdominal pain, and her urine output was minimal. A bladder scan showed more than 500 mL of residual urine. She was hemodynamically stable, but physical examination revealed mild abdominal distention and tenderness in the suprapubic region. Laboratory testing showed a sharp rise in serum creatinine and a drop in hematocrit.

Computed tomography of the abdomen revealed a hematoma measuring 15 by 15 cm within the paracolic gutter and pelvis, compressing the bladder and causing left-sided hydronephrosis (Figure 1). Her laboratory abnormalities were therefore interpreted as postrenal acute kidney injury and anemia due to blood loss.

The patient was initially managed conservatively with serial physical examinations, monitoring of the hematocrit, serial imaging studies, and discontinuation of anticoagulation, but the pain and anuria persisted. Repeat computed tomography 15 days after admission showed that the hematoma had expanded, and she now had hydronephrosis on the right side as well, requiring urologic intervention with bilateral nephrostomy tube placement.

The size of the hematoma was evaluated with serial abdominal and pelvic examinations. After several days, her urine output had improved, the nephrostomy tubes were removed, and she was discharged.

RECTUS SHEATH HEMATOMA

Our patient had a giant pelvic hematoma, probably arising from the rectus sheath. This uncommon problem can arise from trauma, anticoagulation, or increased intra-abdominal pressure, but it can also occur spontaneously.¹

In rectus sheath hematoma, a branch of the inferior epigastric artery is injured at its insertion into the rectus abdominis muscle. Symptoms arise if bleeding does not stop spontaneously from a tamponade effect.²

We speculate that in our patient, deep injection of enoxaparin into the abdominal wall injured the inferior epigastric artery, which started the hematoma, and the bleeding was exacerbated by the anticoagulation effect of the enoxaparin.

Another form of pelvic hematoma is retro­peritoneal. It is most commonly caused by trauma but can occur due to rupture of the aorta, compression from tumors, or, infrequently, anticoagulation therapy.³

The role of anticoagulation

Spontaneous pelvic hematoma is usually missed as a cause of abdominal pain in patients on anticoagulation therapy and is mistaken for common acute conditions such as ulcer, diverticulitis, appendicitis, ovarian cyst torsion, and tumor.⁴ It usually develops within 5 days of starting anticoagulation therapy. Symptoms vary depending on the location of the hematoma and are best diagnosed with abdominal computed tomography, with sensitivity as high as 100%.

MANAGEMENT

Conservative management, reserved for patients in stable condition, includes temporarily stopping and reevaluating the risks and benefits of anticoagulation and antiplatelet agents, giving blood transfusions, and controlling pain. If conservative measures fail, options are arterial embolization, stent grafting, and blood vessel ligation.⁵ If these measures fail, patients should undergo surgical evacuation of the hematoma and ligation of bleeding vessels.⁶

TAKE-HOME MESSAGE

Subcutaneous injections, especially of anticoagulants, into the abdominal wall can increase the risk of hematoma. Other risk factors are older age, female sex, and thin body habitus with less abdominal fat.⁷ Healthcare professionals should avoid deep injections into the abdomen and should counsel patients and their caregivers about this, as well. The deltoid region could be a safer alternative.

A 78-year-old woman presented to the emergency department with shortness of breath and palpitations and was found to have atrial fibrillation with rapid ventricular response. Medical therapy with drug therapy and cardioversion proved ineffective. She then underwent atrioventricular node ablation and placement of a pacemaker.

At the time of admission, anticoagulation was started with full-dose enoxaparin, injected subcutaneously on the left side of the abdominal wall, as her CHA₂DS₂-VASc score (http://chadvasc.org) was 5, due to age, female sex, and history of heart failure and hypertension.

Four days after admission, she reported lower abdominal pain, and her urine output was minimal. A bladder scan showed more than 500 mL of residual urine. She was hemodynamically stable, but physical examination revealed mild abdominal distention and tenderness in the suprapubic region. Laboratory testing showed a sharp rise in serum creatinine and a drop in hematocrit.

Computed tomography of the abdomen revealed a hematoma measuring 15 by 15 cm within the paracolic gutter and pelvis, compressing the bladder and causing left-sided hydronephrosis (Figure 1). Her laboratory abnormalities were therefore interpreted as postrenal acute kidney injury and anemia due to blood loss.

The patient was initially managed conservatively with serial physical examinations, monitoring of the hematocrit, serial imaging studies, and discontinuation of anticoagulation, but the pain and anuria persisted. Repeat computed tomography 15 days after admission showed that the hematoma had expanded, and she now had hydronephrosis on the right side as well, requiring urologic intervention with bilateral nephrostomy tube placement.

The size of the hematoma was evaluated with serial abdominal and pelvic examinations. After several days, her urine output had improved, the nephrostomy tubes were removed, and she was discharged.

RECTUS SHEATH HEMATOMA

Our patient had a giant pelvic hematoma, probably arising from the rectus sheath. This uncommon problem can arise from trauma, anticoagulation, or increased intra-abdominal pressure, but it can also occur spontaneously.¹

In rectus sheath hematoma, a branch of the inferior epigastric artery is injured at its insertion into the rectus abdominis muscle. Symptoms arise if bleeding does not stop spontaneously from a tamponade effect.²

We speculate that in our patient, deep injection of enoxaparin into the abdominal wall injured the inferior epigastric artery, which started the hematoma, and the bleeding was exacerbated by the anticoagulation effect of the enoxaparin.

Another form of pelvic hematoma is retro­peritoneal. It is most commonly caused by trauma but can occur due to rupture of the aorta, compression from tumors, or, infrequently, anticoagulation therapy.³

The role of anticoagulation

Spontaneous pelvic hematoma is usually missed as a cause of abdominal pain in patients on anticoagulation therapy and is mistaken for common acute conditions such as ulcer, diverticulitis, appendicitis, ovarian cyst torsion, and tumor.⁴ It usually develops within 5 days of starting anticoagulation therapy. Symptoms vary depending on the location of the hematoma and are best diagnosed with abdominal computed tomography, with sensitivity as high as 100%.

MANAGEMENT

Conservative management, reserved for patients in stable condition, includes temporarily stopping and reevaluating the risks and benefits of anticoagulation and antiplatelet agents, giving blood transfusions, and controlling pain. If conservative measures fail, options are arterial embolization, stent grafting, and blood vessel ligation.⁵ If these measures fail, patients should undergo surgical evacuation of the hematoma and ligation of bleeding vessels.⁶

TAKE-HOME MESSAGE

Subcutaneous injections, especially of anticoagulants, into the abdominal wall can increase the risk of hematoma. Other risk factors are older age, female sex, and thin body habitus with less abdominal fat.⁷ Healthcare professionals should avoid deep injections into the abdomen and should counsel patients and their caregivers about this, as well. The deltoid region could be a safer alternative.

A 78-year-old woman presented to the emergency department with shortness of breath and palpitations and was found to have atrial fibrillation with rapid ventricular response. Medical therapy with drug therapy and cardioversion proved ineffective. She then underwent atrioventricular node ablation and placement of a pacemaker.

At the time of admission, anticoagulation was started with full-dose enoxaparin, injected subcutaneously on the left side of the abdominal wall, as her CHA₂DS₂-VASc score (http://chadvasc.org) was 5, due to age, female sex, and history of heart failure and hypertension.

Four days after admission, she reported lower abdominal pain, and her urine output was minimal. A bladder scan showed more than 500 mL of residual urine. She was hemodynamically stable, but physical examination revealed mild abdominal distention and tenderness in the suprapubic region. Laboratory testing showed a sharp rise in serum creatinine and a drop in hematocrit.

Computed tomography of the abdomen revealed a hematoma measuring 15 by 15 cm within the paracolic gutter and pelvis, compressing the bladder and causing left-sided hydronephrosis (Figure 1). Her laboratory abnormalities were therefore interpreted as postrenal acute kidney injury and anemia due to blood loss.

The patient was initially managed conservatively with serial physical examinations, monitoring of the hematocrit, serial imaging studies, and discontinuation of anticoagulation, but the pain and anuria persisted. Repeat computed tomography 15 days after admission showed that the hematoma had expanded, and she now had hydronephrosis on the right side as well, requiring urologic intervention with bilateral nephrostomy tube placement.

The size of the hematoma was evaluated with serial abdominal and pelvic examinations. After several days, her urine output had improved, the nephrostomy tubes were removed, and she was discharged.

RECTUS SHEATH HEMATOMA

Our patient had a giant pelvic hematoma, probably arising from the rectus sheath. This uncommon problem can arise from trauma, anticoagulation, or increased intra-abdominal pressure, but it can also occur spontaneously.¹

In rectus sheath hematoma, a branch of the inferior epigastric artery is injured at its insertion into the rectus abdominis muscle. Symptoms arise if bleeding does not stop spontaneously from a tamponade effect.²

We speculate that in our patient, deep injection of enoxaparin into the abdominal wall injured the inferior epigastric artery, which started the hematoma, and the bleeding was exacerbated by the anticoagulation effect of the enoxaparin.

Another form of pelvic hematoma is retro­peritoneal. It is most commonly caused by trauma but can occur due to rupture of the aorta, compression from tumors, or, infrequently, anticoagulation therapy.³

The role of anticoagulation

Spontaneous pelvic hematoma is usually missed as a cause of abdominal pain in patients on anticoagulation therapy and is mistaken for common acute conditions such as ulcer, diverticulitis, appendicitis, ovarian cyst torsion, and tumor.⁴ It usually develops within 5 days of starting anticoagulation therapy. Symptoms vary depending on the location of the hematoma and are best diagnosed with abdominal computed tomography, with sensitivity as high as 100%.

MANAGEMENT

Conservative management, reserved for patients in stable condition, includes temporarily stopping and reevaluating the risks and benefits of anticoagulation and antiplatelet agents, giving blood transfusions, and controlling pain. If conservative measures fail, options are arterial embolization, stent grafting, and blood vessel ligation.⁵ If these measures fail, patients should undergo surgical evacuation of the hematoma and ligation of bleeding vessels.⁶

TAKE-HOME MESSAGE

Subcutaneous injections, especially of anticoagulants, into the abdominal wall can increase the risk of hematoma. Other risk factors are older age, female sex, and thin body habitus with less abdominal fat.⁷ Healthcare professionals should avoid deep injections into the abdomen and should counsel patients and their caregivers about this, as well. The deltoid region could be a safer alternative.

A 21-year-old woman with obesity, type 2 diabetes mellitus, and dyslipidemia presented with eruptive lesions on her extremities that first appeared 2 weeks earlier. Yellowish erythematous papules were noted on the extensor surfaces of both arms and thighs (Figure 1).

Skin biopsy study showed foamy histiocytes mixed with streaks of connective tissue in the dermis (Figure 2). Her fasting serum triglyceride level was 10,250 mg/dL (reference range < 150) and her hemoglobin A_1c level was 12.4% (reference range 4%–5.6%). On further questioning, the patient said that she had stopped taking her prescribed antidiabetic medications and fenofibrate a year previously.

A workup for secondary causes of hypertriglyceridemia was negative for hypothyroidism and nephrotic syndrome. She was currently taking no medications. She had no family history of dyslipidemia, and she denied alcohol consumption.

Based on the patient’s presentation, history, and the results of laboratory testing and skin biopsy, the diagnosis was eruptive xanthoma.

A RESULT OF ELEVATED TRIGLYCERIDES

Eruptive xanthoma is associated with elevation of chylomicrons and triglycerides.¹ Hyperlipidemia that causes eruptive xanthoma may be familial (ie, due to a primary genetic defect) or secondary to another disease, or both.

Types of primary hypertriglyceridemia include elevated chylomicrons (Frederickson classification type I), elevated very-low-density lipoprotein (VLDL) (Frederickson type IV), and elevation of both chylomicrons and VLDL (Frederickson type V).^2,3 Hypertriglyceridemia may also be secondary to obesity, diabetes mellitus, hypothyroidism, nephrotic syndrome, liver cirrhosis, excess ethanol ingestion, and medicines such as retinoids and estrogens.^2,3

Lesions of eruptive xanthoma are yellowish papules 2 to 5 mm in diameter surrounded by an erythematous border. They are formed by clusters of foamy cells caused by phagocytosis of macrophages as a consequence of increased accumulations of intracellular lipids. The most common sites are the buttocks, extensor surfaces of the arms, and the back.⁴

Eruptive xanthoma occurs with markedly elevated triglyceride levels (ie, > 1,000 mg/dL),⁵ with an estimated prevalence of 18 cases per 100,000 people (< 0.02%).⁶ Diagnosis is usually established through the clinical history, physical examination, and prompt laboratory confirmation of hypertriglyceridemia. Skin biopsy is rarely if ever needed.

RECOGNIZE AND TREAT PROMPTLY TO AVOID FURTHER COMPLICATIONS

Severe hypertriglyceridemia poses an increased risk of acute pancreatitis. Early recognition and medical treatment in our patient prevented serious complications.

Treatment of eruptive xanthoma includes identifying the underlying cause of hypertriglyceridemia and commencing lifestyle modifications that include weight reduction, aerobic exercise, a strict low-fat diet with avoidance of simple carbohydrates and alcohol,⁷ and drug therapy.

The patient’s treatment plan

Although HMG-CoA reductase inhibitors (statins) have a modest triglyceride-lowering effect and are useful to modify cardiovascular risk, fibric acid derivatives (eg, gemfibrozil, fenofibrate) are the first-line therapy.⁸ Omega-3 fatty acids, statins, or niacin may be added if necessary.⁸

Our patient’s uncontrolled glycemia caused marked hypertriglyceridemia, perhaps from a decrease in lipoprotein lipase activity in adipose tissue and muscle. Lifestyle modifications, glucose-lowering agents (metformin, glimepiride), and fenofibrate were prescribed. She was also advised to seek medical attention if she developed upper-abdominal pain, which could be a symptom of pancreatitis.

A 21-year-old woman with obesity, type 2 diabetes mellitus, and dyslipidemia presented with eruptive lesions on her extremities that first appeared 2 weeks earlier. Yellowish erythematous papules were noted on the extensor surfaces of both arms and thighs (Figure 1).

Skin biopsy study showed foamy histiocytes mixed with streaks of connective tissue in the dermis (Figure 2). Her fasting serum triglyceride level was 10,250 mg/dL (reference range < 150) and her hemoglobin A_1c level was 12.4% (reference range 4%–5.6%). On further questioning, the patient said that she had stopped taking her prescribed antidiabetic medications and fenofibrate a year previously.

A workup for secondary causes of hypertriglyceridemia was negative for hypothyroidism and nephrotic syndrome. She was currently taking no medications. She had no family history of dyslipidemia, and she denied alcohol consumption.

Based on the patient’s presentation, history, and the results of laboratory testing and skin biopsy, the diagnosis was eruptive xanthoma.

A RESULT OF ELEVATED TRIGLYCERIDES

Eruptive xanthoma is associated with elevation of chylomicrons and triglycerides.¹ Hyperlipidemia that causes eruptive xanthoma may be familial (ie, due to a primary genetic defect) or secondary to another disease, or both.

Types of primary hypertriglyceridemia include elevated chylomicrons (Frederickson classification type I), elevated very-low-density lipoprotein (VLDL) (Frederickson type IV), and elevation of both chylomicrons and VLDL (Frederickson type V).^2,3 Hypertriglyceridemia may also be secondary to obesity, diabetes mellitus, hypothyroidism, nephrotic syndrome, liver cirrhosis, excess ethanol ingestion, and medicines such as retinoids and estrogens.^2,3

Lesions of eruptive xanthoma are yellowish papules 2 to 5 mm in diameter surrounded by an erythematous border. They are formed by clusters of foamy cells caused by phagocytosis of macrophages as a consequence of increased accumulations of intracellular lipids. The most common sites are the buttocks, extensor surfaces of the arms, and the back.⁴

Eruptive xanthoma occurs with markedly elevated triglyceride levels (ie, > 1,000 mg/dL),⁵ with an estimated prevalence of 18 cases per 100,000 people (< 0.02%).⁶ Diagnosis is usually established through the clinical history, physical examination, and prompt laboratory confirmation of hypertriglyceridemia. Skin biopsy is rarely if ever needed.

RECOGNIZE AND TREAT PROMPTLY TO AVOID FURTHER COMPLICATIONS

Severe hypertriglyceridemia poses an increased risk of acute pancreatitis. Early recognition and medical treatment in our patient prevented serious complications.

Treatment of eruptive xanthoma includes identifying the underlying cause of hypertriglyceridemia and commencing lifestyle modifications that include weight reduction, aerobic exercise, a strict low-fat diet with avoidance of simple carbohydrates and alcohol,⁷ and drug therapy.

The patient’s treatment plan

Although HMG-CoA reductase inhibitors (statins) have a modest triglyceride-lowering effect and are useful to modify cardiovascular risk, fibric acid derivatives (eg, gemfibrozil, fenofibrate) are the first-line therapy.⁸ Omega-3 fatty acids, statins, or niacin may be added if necessary.⁸

Our patient’s uncontrolled glycemia caused marked hypertriglyceridemia, perhaps from a decrease in lipoprotein lipase activity in adipose tissue and muscle. Lifestyle modifications, glucose-lowering agents (metformin, glimepiride), and fenofibrate were prescribed. She was also advised to seek medical attention if she developed upper-abdominal pain, which could be a symptom of pancreatitis.

A 21-year-old woman with obesity, type 2 diabetes mellitus, and dyslipidemia presented with eruptive lesions on her extremities that first appeared 2 weeks earlier. Yellowish erythematous papules were noted on the extensor surfaces of both arms and thighs (Figure 1).

Skin biopsy study showed foamy histiocytes mixed with streaks of connective tissue in the dermis (Figure 2). Her fasting serum triglyceride level was 10,250 mg/dL (reference range < 150) and her hemoglobin A_1c level was 12.4% (reference range 4%–5.6%). On further questioning, the patient said that she had stopped taking her prescribed antidiabetic medications and fenofibrate a year previously.

A workup for secondary causes of hypertriglyceridemia was negative for hypothyroidism and nephrotic syndrome. She was currently taking no medications. She had no family history of dyslipidemia, and she denied alcohol consumption.

Based on the patient’s presentation, history, and the results of laboratory testing and skin biopsy, the diagnosis was eruptive xanthoma.

A RESULT OF ELEVATED TRIGLYCERIDES

Eruptive xanthoma is associated with elevation of chylomicrons and triglycerides.¹ Hyperlipidemia that causes eruptive xanthoma may be familial (ie, due to a primary genetic defect) or secondary to another disease, or both.

Types of primary hypertriglyceridemia include elevated chylomicrons (Frederickson classification type I), elevated very-low-density lipoprotein (VLDL) (Frederickson type IV), and elevation of both chylomicrons and VLDL (Frederickson type V).^2,3 Hypertriglyceridemia may also be secondary to obesity, diabetes mellitus, hypothyroidism, nephrotic syndrome, liver cirrhosis, excess ethanol ingestion, and medicines such as retinoids and estrogens.^2,3

Lesions of eruptive xanthoma are yellowish papules 2 to 5 mm in diameter surrounded by an erythematous border. They are formed by clusters of foamy cells caused by phagocytosis of macrophages as a consequence of increased accumulations of intracellular lipids. The most common sites are the buttocks, extensor surfaces of the arms, and the back.⁴

Eruptive xanthoma occurs with markedly elevated triglyceride levels (ie, > 1,000 mg/dL),⁵ with an estimated prevalence of 18 cases per 100,000 people (< 0.02%).⁶ Diagnosis is usually established through the clinical history, physical examination, and prompt laboratory confirmation of hypertriglyceridemia. Skin biopsy is rarely if ever needed.

RECOGNIZE AND TREAT PROMPTLY TO AVOID FURTHER COMPLICATIONS

Severe hypertriglyceridemia poses an increased risk of acute pancreatitis. Early recognition and medical treatment in our patient prevented serious complications.

Treatment of eruptive xanthoma includes identifying the underlying cause of hypertriglyceridemia and commencing lifestyle modifications that include weight reduction, aerobic exercise, a strict low-fat diet with avoidance of simple carbohydrates and alcohol,⁷ and drug therapy.

The patient’s treatment plan

Although HMG-CoA reductase inhibitors (statins) have a modest triglyceride-lowering effect and are useful to modify cardiovascular risk, fibric acid derivatives (eg, gemfibrozil, fenofibrate) are the first-line therapy.⁸ Omega-3 fatty acids, statins, or niacin may be added if necessary.⁸

Our patient’s uncontrolled glycemia caused marked hypertriglyceridemia, perhaps from a decrease in lipoprotein lipase activity in adipose tissue and muscle. Lifestyle modifications, glucose-lowering agents (metformin, glimepiride), and fenofibrate were prescribed. She was also advised to seek medical attention if she developed upper-abdominal pain, which could be a symptom of pancreatitis.