Case Description
A 13-year-old multi-racial male presented with 1-week history of fatigue, generalized aches and pains, bruising, nose bleeds and fever. He had no lymphadenopathy or hepato-splenomegaly, and investigations showed an absolute neutrophil count of 240/mm3, platelets of 6000/cm, and Hb 8.2 gm/dL. A bone marrow aspirate was negative for malignancy and confirmed the diagnosis of very severe aplastic anemia. As outcomes after matched unrelated donor (MUD) and matched related donor (MRD) HSCT are nearly identical, it was decided to pursue treatment with HSCT.2, 3 A 10/10 HLA MUD was identified and the patient received conditioning with fludarabine, alemtuzumab and cyclophosphamide and tacrolimus for GvHD prophylaxis.3 He engrafted on day +18 and had full donor chimerism at day +30.
Around day +28 he was diagnosed with acute skin GvHD (stage 1 grade 1) and treated with topical steroids and topical tacrolimus with good response. However, recurrence of acute GvHD around day +105 (stage 2, grade 1) was treated with oral steroids with good response. Recurrence of rash around day + 271 in both groins and axillae (Figure 1 ) prompted a punch biopsy which showed psoriasiform hyperplasia with spongiosis and superficial perivascular lympho-histiocytic infiltrate after which topical treatments were stopped leading to improvement of the skin rashes. He again presented on day + 320 with raised erythematous maculopapular rash across his trunk and extremities (Figure 1), attributed to acute GvHD (stage 3, grade 2) and treated with systemic plus topical steroids and topical tacrolimus. A repeat biopsy again showed spongiform dermatitis, but now with neutrophilic and eosinophilic infiltrates, suggestive of possible infection for which he was also started on 10-day course of Cefdinir. His rash improved by day + 330.
Unfortunately, after recurrence of skin rashes on weaning of steroids, he was diagnosed with steroid dependent acute GVHD and treated with 2 doses of rabbit anti-thymocyte globulin (rATG 2.5 mg/kg/dose) with a complete response for 4 weeks, followed by recurrence while weaning steroids again around day +391. Immunophenotyping showed CD3 cells at 17.6%, CD4-12.7%, CD8- 3.0%, CD19 -67.6%, ALC-1338 cells/mm3 and NK cells 12.5% with normal B-cell activating factor level (753 pg/mL). He was given weekly rituximab infusions for 4 weeks, after which he stayed in remission for about 2 months before flaring up again around day + 482. Topical triamcinolone and tacrolimus were continued, and trimethoprim-sulfamethoxazole was switched to pentamidine. Topical terbinafine was started for a possible fungal infection and vitamin-D cream was also prescribed to apply to affected areas. Skin findings improved with these interventions, but he continued to have recurrences especially in intertriginous zones.
On day + 552, he presented with acute worsening of rash with erythema and desquamation (Figure 1) and a skin biopsy showed spongiotic dermatitis without concern for GvHD and the diagnosis of SDRIFE was made (Figure 2) . The patient was advised to stop utilizing topical tacrolimus and to only continue utilizing topical steroid. A fast wean of systemic tacrolimus was also begun. With these changes, the patient’s skin findings dramatically improved, and rashes ceased almost immediately. He had no recurrence of rashes in the intertriginous areas.