SG21 Recalcitrant Darier disease with severe pain, chronic infection and multisystem complications: therapeutic challenges and the role of radiotherapy

Abstract

Darier disease (DD) is a rare autosomal dominant disorder of keratinization associated with significant morbidity, recurrent infection and limited evidence-based treatment options. We describe a case in a 55-year-old woman with extensive disease and treatment resistance. DD was diagnosed in childhood, limited to the hands. It gradually progressed to affect the trunk and upper and lower limbs with sparing of the face and neck. Management was complicated by chronic colonization with methicillin-resistant Staphylococcus aureus, anaerobic organisms and Pseudomonas species, resulting in recurrent superinfection, severe pain and pruritus. Previous systemic treatments included acitretin, isotretinoin, ustekinumab, guselkumab, tofacitinib and oral prednisolone, all without sustained benefit. Extensive topical therapies and antiviral prophylaxis were also ineffective. Disease progression, severe pain and debilitating pruritus necessitated admission. Punch biopsy demonstrated histological features consistent with superinfected DD, with suprabasal acantholysis, corps ronds and grains, and surface neutrophilic exudate with coccobacterial colonies. Herpes simplex virus polymerase chain reaction was negative. Admission was complicated by a drug-induced liver injury due to antibiotics. Multiple subsequent admissions for severe flares followed over a 6-month period. Multidisciplinary input was required. Superficial radiotherapy (70 kV) to a dose of 20 Gy in 10 fractions was delivered over a 2-week period to a selected area of the left anterior thigh, resulting in dramatic localized improvement with demonstrable smoothening of the skin. Based on a prolonged response at 3 months, she is proceeding to total-skin electron therapy. Superficial radiotherapy provided a beneficial local effect in our patient and is an option for severe recalcitrant DD. Although there is a known low risk of radiation-induced malignancy, there are also malignancy risks associated with systemic treatments and with prolonged inflammation. This highlights the burden of severe DD, limitations of current systemic therapies and the potential role of radiotherapy as a useful option in recalcitrant disease.