Generalized pustular figurate erythema first report in two COVID‐19 patients on hydroxychloroquine

Abstract

Dear Editor, Generalized pustular figurate erythema (GPFE) is a distinctive severe cutaneous drug reaction with widespread urticarial or edematous plaques scattered over the entire body that become topped with non-follicular pustules that evolve into erythematous and sometimes atypical targetoid plaques converging into annular and arcuate patterns prominent on the trunk and extremities.1 It has been linked with medications, especially hydroxychloroquine. We describe two COVID-19 patients on hydroxychloroquine who developed this eruption 2 and 3 weeks after the onset of hydroxychloroquine. This report is the first to our knowledge of COVID-19 patients on hydroxychloroquine developing GPFE. A 64-year-old man (case 1) with diffuse large B-cell lymphoma undergoing chemotherapy developed bilateral pneumonia from SARS-CoV-2, as did a 60-year-old woman (case 2) with a history of rheumatoid arthritis on etanercept and prednisone (5 mg/days). Diagnosis was rendered by real-time reverse transcriptase-polymerase chain reaction from a nasopharyngeal swab. Both were treated with the same protocol of hydroxychloroquine (400 mg twice a day first day followed by 200 mg twice a day for 10 days) and lopinavir/ritonavir (200 mg/50 mg twice a day) and also teicoplanin, with the woman also given azithromycin. Two to three weeks after starting these medications, each developed a pruritic purpuric erythematous rash with non-follicular pustules, on the trunk and limbs, with intense involvement of armpits and scalp (Fig. 1a–d, case 1). The woman also had intense involvement of neck and face and targetoid lesions on the back (Fig. 1e, case 2). Nikolsky's sign was negative in both; neither had mucosal involvement nor fever. A punch biopsy specimen was obtained from each of them and they both received 0.05% betamethasone dipropionate cream twice a day, loratadine (10 mg/days) and methylprednisolone (40 mg/days), with slow resolution over 4 weeks. In both cases the skin biopsy specimens revealed an acanthotic epidermis with parakeratosis and numerous intracorneal, subcorneal and intraepidermal pustules. Exocytosis of neutrophils and mild spongiosis were present at the periphery of the intraepidermal pustules. The upper dermis showed mild edema with erythrocyte extravasation, dilated capillaries and perivascular lymphocytic infiltrated with occasional neutrophils and rare eosinophils (Fig. 2a–d, case 1; E-H, case 2). COVID-19 patients are being carefully monitored for cutaneous manifestations, as the infection itself may produce suggestive skin findings, which need to be distinguished from drug eruptions.1-3 GPFE has characteristic varied morphology that is reminiscent of both AGEP with its pustulosis and Stevens-Johnson syndrome/toxic epidermal necrolysis with its targetoid component.1, 4-6 Hence patients with it have been labelled as having atypical AGEP or AGEP/Stevens-Johnson syndrome/toxic epidermal necrolysis overlap. Unlike AGEP, which has an onset typically within 48 h of ingestion, GPFE is characterized by an onset of 2–3 weeks, as seen in the two patients herein described. AGEP has been linked with many medications, including teicoplanin and lopinanvir that were taken by the patient, but infections may also be occasional triggers.4-7 Patch testing is often positive in AGEP with confirmation of the culprit drug; however, it can cause recurrence of the skin eruption.8 We report GPFE in two patients with COVID-19. Cutaneous manifestations associated with COVID-19 have been classified into clincial patterns,2, 3 which are distinct from GPFE. Clinicians should be aware of this severe cutaneous drug reaction linked possibly with hydroxychloroquine in two COVID-19 patients. The authors report no conflict of interest. None.

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