Pyoderma gangrenosum secondary to azacitidine in myelodysplastic syndrome

Abstract

A 66-year-old female was diagnosed with myelodysplastic syndrome (MDS), specifically refractory cytopenia with multilineage dysplasia. Her bone marrow demonstrated 3% blasts with a complex karyotype and she had transfusion-dependent anaemia and thrombocytopenia. She was started on azacitidine for very high-risk MDS, as determined by her Revised International Prognostic Scoring System score.The first cycle of azacitidine was well tolerated. Three days into her second cycle, multiple erythematous, painful pustular plaques with a violaceous border and central haemorrhagic crusting appeared on her lips, inner nose and upper arms (top). Empirical ciprofloxacin and clindamycin had no clinical benefit and the lesions then progressed to involve her forearms, with three dominant lesions 3-4 cm in diameter.A skin biopsy demonstrated a neutrophilic infiltrate with marked acute inflammation and reactive changes (bottom); microbiological studies were negative. The clinical and pathological presentation was in keeping with pyoderma gangrenosum (PG). She was treated with prednisone and colchicine, and the azacitidine was withheld for 2 months with subsequent healing of the lesions. The forearm lesions recurred when re-challenged with azacitidine, but promptly responded to a second course of prednisone.Neutrophilic dermatoses, including Sweet syndrome and PG, are uncommon but well-documented dermatological sequalae of MDS. However, given the recurrence of skin lesions with therapy, the clinical and pathological picture was most in keeping with PG secondary to azacitidine, rather than to the underlying disease. PG in MDS has also been linked to the administration of granulocyte colony-stimulating factor. While our patient's skin lesions were controlled with concurrent colchicine and corticosteroids, her MDS did not improve with azacitidine and as a result, this drug was stopped after five cycles.

Drug-induced pyoderma gangrenosum: a model to understand the pathogenesis of pyoderma gangrenosum

“…Cases of drug‐induced PG were mainly gathered from PubMed searches using a variety of combined search terms including ‘pyoderma gangrenosum’, ‘drug‐induced pyoderma gangrenosum’, ‘neutrophilic dermatosis’, ‘treatment’ and ‘therapy’. A list of cases of drug‐induced PG is provided in Table and the proposed pathogenic mechanisms for each drug are illustrated in Figure .…”

Azacitidine Related Pyoderma Gangrenosum

“…To our knowledge, only very few cases of PG associated to Azacitidine injections were reported in the literature [6,7]. Here we report a case of a 54 year-old male with of Azacitidine induced PG.…”

Lobular neutrophilic panniculitis associated with DNA methyltransferase inhibitors in the treatment of myeloid disease

“…Neutrophilic dermatoses including pyoderma gangrenosum and Sweet syndrome are associated with myeloid disorders such as MDS or AML and may be manifestations of underlying hematologic disease or medication reactions . Previous reports have demonstrated a range of clinical presentations from typical Sweet syndrome or pyoderma gangrenosum to atypical variants, including more severe, bullous manifestations . Histologically, most cases present with neutrophilic infiltrates in the upper half of the dermis, with occasional secondary involvement of the panniculus termed “secondary neutrophilic panniculitis”; however, there are infrequent reports of primary neutrophilic infiltrate of the subcutaneous tissue, or “primary neutrophilic panniculitis,” arising in the setting of myeloid disease.…”

“…There were no other changes to medications, which included deferasirox, ondansetron, aspirin, cholecalciferol, and tamsulosin. A 6,7,11 Histologically, most cases present with neutrophilic infiltrates in the upper half of the dermis, with occasional secondary involvement of the panniculus termed "secondary neutrophilic panniculitis" 14 ; however, there are infrequent reports of primary neutrophilic infiltrate of the subcutaneous tissue, or "primary neutrophilic panniculitis," arising in the setting of myeloid disease.…”