Acute generalized exanthematous pustulosis and Stevens-Johnson syndrome overlap due to hydroxychloroquine: a case report

Abstract

Background Since the World Health Organization declared a global pandemic due to the novel coronavirus disease2019, there have been targeted efforts to establish management modalities. Hydroxychloroquine has been suggested as a possible treatment; however, it is associated with multiple adverse reactions. We report a rare case of a patient with acute generalized exanthematous pustulosis with Stevens-Johnson syndrome due to hydroxychloroquine. Acute generalized exanthematous pustulosis is characterized by acute onset of a generalized rash that is pustular and erosive in nature, affecting limbs; trunk; face; and, less often, mucosal membranes. Although rare, it is important to be mindful of this side effect because the diagnosis is often delayed, and the disease has the potential to be life-threatening. Case presentation A 68-year-old American woman presented to our hospital with a painful, rapidly spreading rash. Its morphologic features included erythema multiforme–like lesions with extensive skin sloughing in various regions of the head, neck, and trunk and mucosal involvement. Her Nikolsky sign was negative, and she had no evidence of lesions on areas of skin trauma. Four weeks prior, she had been initiated on hydroxychloroquine for a presumed diagnosis of cutaneous sarcoidosis. Three punch biopsies of the head and neck area revealed subcorneal pustules consistent with acute generalized exanthematous pustulosis. Treatment began with high doses of methylprednisolone, leading to only minimal improvement of existing areas and ongoing spread to new areas. Treatment with intravenous immunoglobulin was initiated, at which point disease stability was achieved. The patient’s rash ultimately resolved, as did her cutaneous pain and pruritus. Conclusions Among many potential adverse reactions involving hydroxychloroquine, cutaneous side effects are varied and can lead to significant morbidity or even death. The drug is currently being investigated in a multitude of trials for coronavirus disease2019 treatment, prevention, and prophylaxis after exposure to severe acute respiratory syndrome coronavirus 2. Acute generalized exanthematous pustulosis is a rare side effect of hydroxychloroquine, and even fewer cases demonstrate histologic evidence of acute generalized exanthematous pustulosis while clinically presenting with Stevens-Johnson syndrome. Patients who develop Stevens-Johnson syndrome/toxic epidermal necrolysis require best supportive care with aggressive fluid and electrolyte replacement and prevention of further breakdown of the skin barrier. With the potential of widespread hydroxychloroquine use, it is important that providers be aware of its potential severe adverse drug reactions.

The place of hydroxychloroquine in modern dermatology

“…Skin pruritus has also been reported, although it is worth noting that this may be a symptom of CLE [79,82]. HCQ may induce a drug reaction in the form of toxic epidermal necrolysis or acute generalized exanthematous pustulosis (AGEP), and although the latter is uncommon, HCQ is mentioned as one of the most frequent causes [79,83]. Photosensitivity, urticaria, erythema multiforme or drug reactions with eosinophilia and systemic symptoms (DRESS), hair loss, hair discoloration and stomatitis have been reported occasionally [79].…”

“…Opisywany był również świąd skóry, chociaż warto zauważyć, że może to być objaw CLE [79,82]. HCQ może wzbudzić reakcje polekowe o typie toksycznej nekrolizy naskórka lub ostrej uogólnionej osutki krostkowej (acute generalized exanthematous pustulosis -AGEP) i chociaż ta ostatnia nie jest częstym powikłaniem, to HCQ wymieniana jest jako jedna z najczęstszych jej przyczyn [79,83]. Sporadycznie opisywane są: nadwrażliwość na światło, pokrzywka, rumień wielopostaciowy lub reakcja polekowa z eozynofilią i objawami ogólnymi (drug reaction with eosinophilia and systemic symptoms -DRESS), łysienie, przebarwienie włosów, zapalenie błony śluzowej jamy ustnej [79].…”