Haemorrhagic bullous pyoderma gangrenosum following COVID-19 vaccination.

Dear Editor,

Pyoderma gangrenosum (PG) is a destructive, inflammatory, neutrophilic dermatosis and often associated with an underlying systemic disease. PG is characterized by a rapidly progressive ulcer with a purulent, necrotic base and a raised, violaceous, undermined border developing from the breakdown of painful nodules or pustules. , Clinical variants of PG include ulcerative, bullous, pustular, vegetative and peristomal. , There have been various cutaneous reactions reported after COVID‐19 vaccination. However, to our knowledge, there has been no COVID‐19 vaccination‐associated PG reported.

A 46‐year‐old otherwise healthy male presented with fever (38.4°C) and painful blisters on the extremities for 5 days. He had received the first‐dose ChAdOx1 nCov‐19 (Oxford‐AstraZeneca) vaccination 2 weeks before presentation. Dermatologic examination revealed numerous haemorrhagic blisters on his hands, elbows, knees, legs and feet and scattered necrotic ulcers with granulomatous bases and undermined edges developing after blisters ruptured (Fig. 1a, b, and c). Histopathological examination obtained from the ulcer edge on the left leg showed neutrophilic and lympho‐histiocytic infiltrates in the undermining oedematous ulcer edge and underlying dermis (Fig. 1d). A direct immunofluorescence study and blood and tissue cultures for bacteria, fungus, mycobacteria, and herpes virus were all negative. Laboratory testing revealed normal liver and renal function, complete blood count, prothrombin time, and activated partial thromboplastin time, except for mild elevated C‐reactive protein, D‐dimer (873 ng/mL FEU; reference range, ≤ 550 ng/mL) and fibrinogen (483 mg/dL; reference range, 190–380 mg/dL) levels. Anti‐nuclear antibody and anti‐basement membrane zone antibody were unremarkable. The workup of vasculitis showed normal anti‐neutrophil cytoplasmic antibody, protein‐C, protein‐S, anti‐phospholipid antibodies and cryoglobulin levels. Negative anti‐platelet‐factor 4 testing further excluded the possibility of vaccine‐induced thrombotic thrombocytopenia. Haemorrhagic bullous PG was diagnosed on clinical and histopathologic grounds. The patient did not have any underlying diseases, such as haematological malignancy, inflammatory bowel disease (IBD) and autoimmune disease. Naranjo causality assessment showed an association between vaccination and PG. The patient was treated with intravenous methylprednisolone (1 mg/kg/day) and cyclosporin (150 mg/day) for 1 month during admission. Repeated wound cultures did not identify microorganisms. The ulcerated lesions gradually healed without developing new blisters (Fig. 1e); oral methylprednisolone and cyclosporin were tapered to 8 mg/day and 100 mg/day, respectively, during his last follow‐up, 1 month after discharge.

Figure 1

COVID‐19 vaccination‐associated haemorrhagic bullous pyoderma gangrenosum. (a–c) Numerous haemorrhagic blisters and scattered necrotic ulcers with granulomatous bases and undermined edges on the lower legs and feet. (d) Histopathology showing an undermining ulcer edge with subepidermal oedema, haemorrhage and dermal inflammatory infiltrates including numerous neutrophils (haematoxylin–eosin, original magnification ×200). (e) Healed ulcerated lesions without new blisters after 1 month of treatment. [Colour figure can be viewed at wileyonlinelibrary.com]

Bullous PG manifesting with a growing central necrotic and haemorrhagic blister has rarely been reported. PG is a diagnosis of exclusion, which is made primarily based on clinical features. A skin biopsy taken from an active ulcer border with tissue cultures to exclude other aetiologies of ulcerations and infections is recommended. Systemic corticosteroids are first‐line therapies with cyclosporine as a second‐line treatment. , PG often has an associated systemic disease, such as IBD, monoclonal gammopathy, hematologic malignancy, arthritis, infection and collagen‐vascular disease, while bullous PG is significantly associated with haematological malignancies. , The results of autoimmune and tumour markers, protein electrophoresis, peripheral blood smear, colonoscopy and whole body computed tomography in this patient were unremarkable. PG following SARS‐CoV‐2 infection and other neutrophilic dermatoses after COVID‐19 vaccination have been documented. , , COVID‐19 vaccines can induce intensive T‐ and B‐cell responses against SARS‐CoV‐2 and unwanted off‐target immune‐stimulatory effects, subsequently eliciting cutaneous T‐cell‐dependent disorders. T‐cell expansion and inflammatory cytokines play a role in PG. Systemic corticosteroids are first‐line therapies, either as an intravenous high dose (0.5–1 mg/kg/day) or pulse corticosteroid (1000 mg/day). , Cyclosporine (2.5–5 mg/kg/day) is used as a second‐line treatment, and other immunosuppressive agents, including azathioprine, methotrexate and mycophenolate mofetil, have been used. , Biologics, including anti‐tumour necrosis factors (anti‐TNFs) and interleukin‐1 receptor antagonists (IL‐1RAs), have been used to treat refractory PG effectively. , Considering the response to COVID‐19 vaccination may be reduced while receiving systemic immunomodulatory therapies, systemic corticosteroids at a prednisone‐equivalent dose of ≥20 mg/day, methotrexate and mycophenolate mofetil are recommended to be hold for 1–2 weeks in patients undergoing COVID‐19 vaccination, while anti‐TNFs or IL‐1RAs may be alternative options with less interfering the antibody titers.

We reported a case of PG following COVID‐19 vaccination, which posed a diagnostic challenge. The present case highlights the characteristic manifestations of haemorrhagic bullous PG, which is both an uncommon clinical variant of PG and a rare cutaneous reaction to COVID‐19 vaccine. Early recognition and adequate immunomodulants treatment often yield a favourable prognosis.

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Conflict of interest

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