Hatice Sanli

Vitiligo after Hematopoietic Cell Transplantation: Six Cases and Review of the Literature

Aim: To investigate the prevalence and clinical characteristics of vitiligo after allogeneic hematopoietic cell transplantation (AHCT). Methods: The development of vitiligo was analyzed among 421 patients who underwent AHCT in Ibni Sina Hospital (University of Ankara) between 1988 and 2004. Results: Among 421 patients, we describe 6 with generalized vitiligo occurring after AHCT for chronic myelogenous leukemia. Five of them had severe chronic graft-versus-host disease (GVHD). Vitiligo was accompanied by alopecia areata and acquired ichthyosis in 2 patients with GVHD. Conclusion: Melanocyte destruction caused by the autoimmune reactions triggered by chronic GVHD as well as a genetic predisposition might have played a role in the development of vitiligo in our patients. These data support the hypothesis that vitiligo is an autoimmune entity.

Evaluation of nail involvement in patients with chronic cutaneous graft versus host disease: a single-center study from Turkey.

Although graft versus host disease (GVHD) is associated with a myriad of cutaneous signs, nail involvement is rarely mentioned in the literature. This study was conducted at the Department of Dermatology and The Bone Marrow Transplantation Unit of Hematology. All patients were examined clinically for presence of nail abnormalities. Severity of nail involvement was assessed as mild or severe. Of 28 patients diagnosed with chronic cutaneous GVHD, 14 had nail manifestations. Longitudinal ridging was the most frequently observed nail change on both the fingernails and the toenails. Severe nail changes such as ptergyium and onicoatrophy were noted in a few patients. As a result we could not find any relationship between nail changes and clinical severity but there was a relationship between nail changes and duration of disease. Nail manifestations could be responsible for considerable morbidity.

Clinical manifestations of cutaneous graft-versus-host disease after allogeneic haematopoietic cell transplantation: long-term follow-up results in a single Turkish centre.

The aim of this study was to evaluate the clinical manifestations of cutaneous graft-versus-host disease (GVHD) developed after allogeneic haematopoietic cell transplantation. In all, 67 patients were evaluated: 49 patients developed acute GVHD, 17 patients developed de novo chronic GVHD and 29 developed secondary chronic (15 limited, 14 progressive) GVHD following acute cutaneous GVHD. Of the 46 patients with chronic GVHD, lichenoid lesions were observed in 32 and sclerodermoid lesions were observed in 12. In four patients with sclerodermoid cutaneous GVHD, these lesions occurred after a lichenoid phase. Oral lesions were present in 61% of the patients and six of them had only oral mucosal involvement without any skin lesions. Nail lesions were observed in 31% of the patients. During the follow-up period 15 patients with GVHD died and in 7 of them the cause of death was related to chronic GVHD. In conclusion, GVHD has a wide spectrum of cutaneous manifestations, which can be used as an important tool for the early diagnosis of the disease.

Long-term results of rituximab–intravenous immunoglobulin combination therapy in patients with epidermolysis bullosa acquisita resistant to conventional therapy

Abstract Background: Epidermolysis bullosa acquisita (EBA) is a rare subepidermal bullous disease. Long-term remission in this disease is difficult using current treatments, unlike that in patients with other autoimmune bullous diseases. Objective: We retrospectively evaluated the effectiveness and side effects of rituximab–intravenous immunoglobulin (IVIg) combination treatment in five patients with EBA resistant to conventional treatment. Patients and methods: Rituximab (375 mg/m2) was administered for four consecutive weeks to four patients, and their treatment continued with IVIg at a dose of 2 g/kg/month. One patient received two cycles of rituximab for three consecutive weeks, IVIg in the fourth week, followed by monthly IVIg administrations as in the other patients. Results: The total number of IVIg therapy cycles ranged from 10 to 26 (mean 19.4). Mean skin involvement, mucosal involvement, and disease severity scores decreased after a mean follow-up of 22.6 months (range, 10–28 months). In an analysis performed during months 24–28, the number of CD19-positive B cells was found to be below the normal reference range in four patients. Limitations: This was a retrospective study with a limited number of patients. Conclusion: Rituximab–IVIg combination treatment seems to be effective and safe for treating patients with EBA resistant to conventional treatments.

Acquired ichthyosis associated with type 1 diabetes mellitus

Acquired ichthyosis is an uncommon disease which is characterized by symmetric scaling of the skin. Acquired ichthyosis has been described in association with a variety of underlying causes, including malignancies, drugs, infections, endocrine, metabolic and autoimmune diseases. Acquired ichthyosis associated with diabetes mellitus has been reported only in one case. We report the case of a new-onset diabetes mellitus with a one-month history of generalized acquired ichthyosis and palmoplantar keratoderma corroborated with skin biopsy, which completely disappeared after regulation of blood glucose levels with insulin therapy.

Simultaneous onset of chronic graft versus host disease and alopecia areata following allogeneic haematopoietic cell transplantation.

Sir, Chronic graft versus host disease (cGVHD) is a systemic complication that occurs after allogeneic haematopoietic stem cell or solid organ transplantation. Its incidence after allogeneic haematopoietic cell transplantation ranges between 27% and 72% (1). The immune system itself is a major target for cGVHD and the development of dysfunction may lead to autoimmune disorders. The association of vitiligo, myasthenia gravis, thrombocytopenia, autoimmune haemolytic anemia and polymyositis with cGVHD has been reported previously (2 – 6). We present three patients with alopecia areata (AA) occurring during the course of cGVHD. To the best of our knowledge, such an association has not been reported previously.

Hyperkeratosis of the nipple associated with chronic graft versus host disease after allogeneic haematopoietic cell transplantation.

Sir, Hyperkeratosis of the nipple and the areola (HNA) is a rare, benign condition characterized by asymptomatic hyperkeratosis and hyperpigmentation affecting the nipples and/or the areolae mammae (1 – 3). It may be idiopathic or associated with diseases such as ichthyosis, acanthosis nigricans, Darier’s disease or endocrinopathies. A few cases have also been reported related to internal malignancies, cutaneous T-cell lymphoma, or use of drugs (oestrogen and spironolactone) (4 – 7). We report here a case of HNA that developed during chronic cutaneous graft versus host disease (GVHD) following allogeneic peripheral blood stem cell transplantation.

Extracorporeal photochemotherapy in mycosis fungoides

OBJECTIVES Extracorporeal photo-chemotherapy (ECP, photopheresis) is an approved treatment modality for mycosis fungoides (MF). Our aim is to present our ECP data for MF. METHODS We retrospectively evaluated 50 MF patients who received ECP for clinical activity, toxicity, and response and outcome rates, and we compared these with combination therapies. RESULTS The overall response rate (ORR) was 42% (21/50), while the median time to response was 11months (range, 3-48months). Ten of the responders (48%) had 3 or more treatment lines prior to ECP. Eight patients (16%) had adverse events related to ECP. The overall survival (OS) of 50 patients was 72months (range, 3-211). There was no statistically significant difference in the OS in early-stage vs late-stage patients (77 vs 69months, P=0.077). The stage 3 and 4 patients received an average of 31 cycles compared to 55 cycles in stage 1 and 2 patients (P=0.006). The increased extent of ECP was not correlated with the response. Combined treatment with ECP significantly improved the OS (84months vs 62months, P=0.005). DISCUSSION A low frequency of side effects and improved OS observed in combination therapy makes ECP a favorable option for treating MF.

Clinical aspects of sclerodermatous type graft-versus-host disease after allogeneic hematopoietic cell transplantation

OBJECTIVE We aimed to evaluate the clinical features of sclerodermatous chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (AHSCT). METHODS We retrospectively analyzed 423 patients who underwent AHSCT. We assessed age, sex, pre-transplant diagnosis, conditioning regimen, GVHD prophylaxis, and occurrence of acute GVHD (aGVHD), chronic lichenoid and chronic systemic GVHD, and clinical properties of sclerodermatous GVHD. RESULTS Sclerotic skin lesions developed in 22 patients after a mean of 752±647 days (median 480). aGVHD appeared in 17 patients, with hepatic involvement in 2, gastrointestinal tract involvement in 2 and skin involvement in 13 of these patients. Extensive chronic GVHD (liver, pulmonary, skin and oral mucosa) developed in 12 patients. Sclerosis was generalized in 19 patients (86.4%) and localized in 3 patients (13.6%). Leopard skin eruption appeared in 8 (36.4%) of the 19 patients with generalized sclerodermatous changes. In most cases, sclerotic lesions appeared on the trunk, and distal parts of the extremities were spared. Eight patients (36.4%) progressed from lichenoid to sclerodermatous lesions, 2 (9.1%) with lichenoid and sclerodermatous phases together and 12 (55.5%) with de novo sclerodermatous lesions. Five patients died because of late transplant-related complications. CONCLUSION Sclerodermatous GVHD has a late onset and may be quite disabling. Unlike scleroderma, acral involvement is seen rarely. Although most lesions do not disappear in the course of the disease, most patients have a good prognosis.

Allogeneic hematopoietic stem cell transplantation for refractory mycosis fungoides (MF) and Sezary syndrome (SS)

Cutaneous T cell lymphoma is a heterogeneous group of lymphoproliferative disorders with different clinical behavior and prognosis in which malignant T cells accumulate in the skin. In the relapsed/refractory stage, treatment strategy varies depending on clinical perspective. We retrospectively evaluated advanced stage relapse or refractory mycosis fungoides and Sezary syndrome patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) at our hospital. The overall response rate was 25%, while the disease progressed and relapsed after transplant in 38% of patients. Allo-HSCT may be a reasonable treatment option in the relapsed/refractory stage.