Acute generalized exanthematous pustulosis induced by hydroxychloroquine.

Abstract

Acute generalized exanthematous pustulosis (AGEP), an adverse drug reaction, is usually triggered by antibiotics,1, 2 although several drugs are reported to be associated with this condition. Hydroxychloroquine (HCQ) is usually considered as one of the first-line treatment option for autoimmune diseases, but recently several articles reported that HCQ is used as a possible alternative treatment for coronavirus disease 2019 (COVID-19).1 AGEP triggered by hydroxychloroquine is uncommon. Herein, we report a case with AGEP induced by HCQ. A 63-year-old female patient was presented with generalized eruption of pustules for 2 days. She was diagnosed with fever of unknown origin since 6 months ago and underwent empirical antibiotic treatment with flomoxef and azithromyzin for 3 days. Then, systemic prednisolone 10 mg once daily was administrated for suspecting adult-onset Still's disease. HCQ 200 mg twice daily was administered for covering possible viral exanthema and possible autoimmune-related diseases. Seventeen days after administration of HCQ treatment, the itchy rash appeared on the face, trunk, folds, and four limbs within 1 day. Intermittent fever up to 38.4°C was noticed. Physical examination revealed scarlatiniform erythema, with several scattered, small nonfollicular pustules distributed over bilateral palms, face, trunk, back, inguinal areas, and four limbs (Figure 1A,B). Mild fever Lab data demonstrated leukocytosis with left shift (white blood cells = 43,930/mm3, normal <10,000; segment form = 93.4%). Skin biopsy was preformed from abdomen. Histopathological examination revealed spongiosis and superficial perivascular infiltration, numerous neutrophils scattered over epidermal and superficial dermis. Marked subcorneal and intracorneal separations were noticed (Figure 1C,D). The periodic acid-schiff (PAS) stain was negative for fungus. Based on the clinical and the histopathological findings, the patient was diagnosed with AGEP. Drug history was reviewed and scored according to the algorithm for assessment of drug causality in AGEP. Discontinuation of HCQ immediately and prescription of methylprednisolone 40 mg three times daily were administered for 1 week. The lesions resolved rapidly after administration of systemic steroid. AGEP is characterized by the sudden onset of an eruption of numerous small, primarily nonfollicular, sterile, and pin-sized pustules, arising within large areas of edematous erythema base. AGEP is usually associated with high fever, peripheral neutrophilia, and acute evolution with spontaneous resolution within 1–2 weeks.2 The proliferation and migration of drug-specific cluster of differentiation CD4 and CD8 T cells play a critical role in the development of AGEP.3 Compatible to our case, the onset time of HCQ-induced AGEP is ranging from 2 to 3 weeks,2 compared to which is usually longer than that of other beta-lactam antibiotics-related AGEP (24–48 hours). It is sometimes hard to differentiate AGEP from generalized acute pustular psoriasis, which is often characterized by history of psoriasis. But both the diseases present intracorneal and subcorneal pustules under histopathological examination. HCQ, usually administered for rheumatoid arthritis, systematic lupus erythematosus, had major side effect of retinopathy and hemolysis in patients with glucose-6-phosphate dehydrogenase deficiency, while cutaneous adverse reactions are uncommon, including alopecia, bullous rash, Stevens–Johnson syndrome and toxic epidermal necrolysis.4 Recently, more cases have been reported as HCQ for treating COVID-19 and numerous studies had started to report that it may cause AGEP.5 In conclusion, we report a case with AGEP induced by HCQ. This report highlights the importance of taking HCQ into consideration when dealing with AGEP. The authors declare no potential conflict of interest.