General Dermatology

Severe Cutaneous Drug Reaction to Hydroxychloroquine Delineated

Dibash Kumar Das, PhD
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Sweet syndrome affects males and females of all ages, but most cases occur in individuals age 30 to 50.13 Sweet syndrome is 3 times more common in females. It is considered idiopathic, but possible triggers include infection, malignancy, autoimmune disorders, and certain medications.13 Approximately 2% of cases are related to pregnancy; it most often arises during the first or second trimester.2 At onset, patients have sudden eruptions of tender, painful plaques or plaque-like nodules.13 The lesions usually appear on the face, neck, trunk, and limbs but occasionally affect the mouth, genitals, and eyes. Common symptoms include fever and arthralgia. Histopathologic examination will reveal neutrophilic infiltrates. Laboratory findings often include leukocytosis, neutrophilia, and elevated erythrocyte sedimentation rate.13 Most cases resolve fairly quickly without treatment, but topical or oral corticosteroids can be used. Sweet syndrome does not appear to harm fetal health.2

Sweet syndrome affects males and females of all ages, but most cases occur in individuals age 30 to 50.13 Sweet syndrome is 3 times more common in females. It is considered idiopathic, but possible triggers include infection, malignancy, autoimmune disorders, and certain medications.13 Approximately 2% of cases are related to pregnancy; it most often arises during the first or second trimester.2

At onset, patients have sudden eruptions of tender, painful plaques or plaque-like nodules.13 The lesions usually appear on the face, neck, trunk, and limbs but occasionally affect the mouth, genitals, and eyes. Common symptoms include fever and arthralgia. Histopathologic examination will reveal neutrophilic infiltrates. Laboratory findings often include leukocytosis, neutrophilia, and elevated erythrocyte sedimentation rate.13 Most cases resolve fairly quickly without treatment, but topical or oral corticosteroids can be used. Sweet syndrome does not appear to harm fetal health.2

The delayed onset of a severe cutaneous reaction to hydroxychloroquine means clinicians may continue to see patients presenting with the symptoms.

Ingestion of hydroxychloroquine results in a severe cutaneous drug reaction delineated as Generalized Pustular Figurate Erythema (GPFE), according to a study published in Dermatologic Therapy.

Researchers have documented a disorder resembling acute generalized exanthematous pustulosis (AGEP). The investigators describe a severe cutaneous adverse reaction with an onset of 2 to 3 weeks after ingestion of hydroxychloroquine. The adverse reaction is distinguishable by its increased severity, increased difficultly to treat, a longer duration, and pathogenic mechanism that differs from the typical AGEP. The researchers highlight this perplexing disorder as generalized pustular figurate erythema (GPFE). Although it can be associated with several medications, it is most strongly associated with hydroxychloroquine.

Hydroxychloroquine, a common anti-malarial drug, has been evaluated as an antiviral agent against coronavirus-19. Clinical examinations have shown a sharp onset of a pruritic eruption indicative of a severe cutaneous drug reaction. GPFE may first present itself as erythematous papules and plaques on the face with facial edema and widespread urticarial plaques on the entire body, with progression of nonfollicular pustules atop erythematous and sometimes uncharacteristic targetoid erythema multiforme-like plaques “converging into arcuate patterns prominent on the trunk, upper and lower extremities,” the investigators wrote.

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Various treatment modalities for GPFE including topical and systemic steroids, other potent topical steroids with oral dapsone or etretinate, may be followed by cyclosporine when GPFE is not responsive.

The authors conclude that “additional experience with GPFE and its treatment can be anticipated to surge as hydroxychloroquine becomes widely utilized in the COVID-19 pandemic.”

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Reference

Schwartz RA, Janniger CK. Generalized pustular figurate erythema a newly delineated severe cutaneous drug reaction linked with hydroxychloroquine (published online April 6, 2020). Dermatol Ther. doi: 10.1111/dth.13380

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