Mucous membrane pemphigoid following reduced intensity conditioning allogeneic haematopoietic SCT for biphenotypic leukaemia

Mucous membrane pemphigoid (MMP) encompasses a group of autoimmune, chronic inflammatory, subepithelial blistering disorders affecting the mucous membranes characterized by deposition of IgG, IgA or C3 on the basement membrane zone (BMZ). There is predilection for involvement of the oropharynx, nasopharynx, larynx, conjunctiva, anogenital and oesophagus with or without skin involvement.1, 2 We report an unusual case of MMP that developed in a gentleman following a reduced intensity conditioning haematopoietic SCT. A 51-year-old gentleman with acute biphenotypic leukaemia, underwent a reduced intensity conditioning haematopoietic SCT. He received a cell dose of CD34 8.49 × 106/kg (PBPCs) from an unrelated male HLA-C mismatched donor. The conditioning protocol comprised fludarabine (30 mg/m2 daily × 5days), i.v. BU (3.2 mg/kg daily × 2 days) and alemtuzumab (20 mg daily × 5 days) with ciclosporin post transplant for GVHD prophylaxis. He had no significant bacterial viral infections in the immediate peri or post transplant period. His days 28, 56 and 100 BM assessment confirmed that he was in morphological remission with full donor chimerism, and he had no evidence of GVHD. Three months post transplant, he presented with a 3-week history of recurrent febrile episodes, sore throat, wt loss and a productive cough with copious mucopurulent sputum. In addition, he developed conjunctivitis with discharge from his eyes. On clinical examination, he was cachectic, with erythematous vesicular lesions on his soft and hard palate. Respiratory examination revealed crepitations bilaterally. His blood count was Hb 8.9, WBC 6.2, neutrophils 5.38, plts 115 and lymphocytes 0.39. He was initially commenced on broad spectrum i.v. antibiotics and antiviral therapy, but he continued to have persistent pyrexial episodes. A high-resolution computer tomographic scan of his chest revealed multiple foci of consolidation and patchy areas of ground glass opacification of both lungs. A bronchoscopy was performed which revealed submucosal nodules throughout the bronchial tree. These lesions were initially thought to be viral in aetiology. However, a bronchoalveolar lavage performed was negative for virology, microbiology and atypical respiratory serology. In view of his ocular symptoms, he had an ophthalmology review and a provisional diagnosis of ocular GVHD was made. He was commenced on topical steroid and lubricant eye drops with limited benefit. He subsequently developed a skin lesion near the lateral canthus of his left eye (Figure 1), which was biopsied. The histology revealed inflammation and granulation tissue. Indirect immunofluorescence analysis of serum detected IgG class anti-BMZ antibodies to a titre of 1/10 localizing to the base of the salt split skin (Figure 2). The IgG anti-BMZ antibodies did not recognize the classical bullous pemphigoid or epidermolysis bullosa acquisita Ags, and a diagnosis of MMP was made on clinical and immunopathological features. He was treated with i.v. Ig (1 g/kg × 2 days) and was subsequently commenced on methylprednisolone at a dose of 1 g/day for 5 days. His corticosteroids were gradually weaned off over a 5-month period. Over the following weeks, there was a significant improvement in his condition with the vesicles in his oropharynx resolving and his ocular symptoms improving. A repeat high-resolution computer tomographic scan performed 1 month later showed a marked reduction in the inflammation of the upper airways. He is presently 19 months post transplant and remains in CR with no evidence of recurrence of MMP. We have reviewed the literature and identified one previously reported case in a 44-year-old female patient with refractory follicular lymphoma who developed MMP 18 months following a reduced intensity conditioning haematopoietic SCT. She was treated with prednisolone (1 mg/kg) once the diagnosis was made and achieved complete resolution of the mucosal lesions within a week.3 Other cases of MMP have also been reported in solid malignancies such as renal cell carcinoma4 or non small cell lung carcinoma.5 Bullous pemphigoid has also been reported in five cases post-allogenic SCT.3 The treatment strategies incorporated predominantly steroids or other means of immunosuppression such as ciclosporin. The most common autoantibodies found in patients with MMP are reactive to BPAG2 and an autoantigen-termed epiligrin which are thought to be associated with internal malignancy.6, 7 MMP has also been associated with certain immunogenic haplotype patterns HLA-DQB1*0301.8, 9 Although the underlying pathogenesis of MMP post-HSCT remains unclear, it is postulated that either following the conditioning regimen or thereafter in patients with GVHD, the basal cells of the epidermis are attacked, which may result in the increased exposure of the BMZ proteins for Ag presentation in susceptible patients. In conclusion, we describe a rare case of mucous membrane pemphigoid developing post-allogeneic transplant for biphenotypic leukaemia. It is important to have a high index of suspicion in patients with extensive mucosal blistering following HSCT or underlying malignancy, and it would be prudent to expedite the diagnosis with early tissue biopsy. The authors declare no conflict of interest.