Haematologica 2002; 87:(03)ECR10
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Keratoderma blenorrhagica, balanitis and uveitis after HLA-B15 mismatched bone marrow transplantation.
Au WY,3 Hon C,2 Lie AKW,1 Yeung CK,3 Ma SY,3 Chan HH3
Departments of Hematology1, Ophthalmology2 and Dermatology3, Queen Mary Hospital, Hong Kong

Correspondence to Dr Au, University Department of Medicine 4/F, Professorial Block, Queen Mary Hospital, Pokfulam Road, Hong Kong. Tel: (852) 2 855 4792. Fax: (852) 2 974 1165. Email: auwing@hotmail.com
A 32-year-old Chinese man with Burkitt's leukemia (HLA: A2 A11 B15 B40 DR4 DR12) underwent bone marrow transplantation (BMT) from his one antigen B15 mismatched mother (HLA: A2 A11 B40 B40 DR4 DR12). Cyclophosphamide and total body irradiation were used for conditioning. Despite cyclosporine and methotrexate, grade IV graft-versus-host disease (GVHD) involving the skin, liver and gut developed with severe diarrhea in particular, and he was treated with steroids, mycophenolate mofeteil and antithymocyte globulin. By day 90, he was afebrile with stable engraftment and mild chronic skin GVHD affecting the torso. However, he developed severe persistent focal exfoliative dermatitis evolving to hyperkeratosis of the palmar and plantar surfaces, reminiscent of keratoderma blenorrhagica (Figure 1 A and B), lasting for several weeks. Repeated skin biopsies showed epidermal thickening and necrosis, dermal perivascular lymphocytic infiltration with upper dermal fibrosis, and scattered basal cell degeneration, attributed to skin GVHD. The rash was accompanied by recurrent oral ulcerations, and multiple shallow, red, moist erosions over the glans penis and prepuce with marginal erythema consistent with balanitis (Figure 1C). A slit lamp examination showed bilateral acute uveitis with anterior chamber cells. There was no clinical or X-ray evidence of sacroilitis, and screening tests for chlamydia infection were negative. He was treated with oral prednisolone, topical steroid cream and eyedrops, and maintained on cyclosporine. For BMT from related donors, mismatch in the A, B and DR locus involve risks of rejection, GVHD and post-transplant lymphoma.1 In our case, due to donor HLA-B homozygosity, the risk is increased only for GVHD, theorectically mediated significantly by donor lymphocytes against HLA-B15 host antigen. Although palmar erythema early after BMT is common, the localization of GVHD to plantopalmar distribution at three months is unusual. Such a feature, with concurrent uveitis and balanitis, is unique among 534 consecutive cases of A, B, DR full-match and 18 cases of 1-antigen mismatch BMT at our institution (matching for HLA C and DQ loci is not performed at our center for related BMT). The palmoplantar predilection, together with inflammation of the eye and external genitalia, is reminiscent of Reiter's syndrome and, to a lesser extent, Behcet's disease. Both diseases are attributed to autoimmune attack on B antigens (HLA-B27 and B5) due to molecular mimicry with gut bacteria antigens.2,3 Incomplete syndromes without joint manifestations are well documented.4 For both entities, gastroenteritis often heralds the skin, eye and joint manifestations.5,6 In our case, gut GVHD and consequent bacteremia may have increased the exposure to host and cross-reacting gut bacterial antigens. Associations between seronegative spondylitis and Behcet's disease with HLA-B15 have both been reported.7,8 HLA-B15 is also linked to immune-mediated skin disorders such as erythema multiforme,9 and vasculitis such as Takayasu arteritis.10 The peculiar pattern and distribution of surface lesions caused by these autoimmune attacks on the HLA-B antigen are likely to be related to differential antigen expression on the skin, orbital and mucosa tissue. The long-term alloimmune and rheumatological consequences in our case remain to be seen.

References

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