Cases reported "Psoriasis"

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1/9. Graft vs autoimmunity following allogeneic non-myeloablative blood stem cell transplantation in a patient with chronic myelogenous leukemia and severe systemic psoriasis and psoriatic polyarthritis.

    OBJECTIVE: No specific therapy exists for autoimmune diseases caused by self-reactive lymphocytes. As shown in experimental animals, which led to pilot clinical studies, elimination of self-reactive lymphocytes can be accomplished with high-dose chemoradiotherapy, followed by autologous stem cell transplantation, by re-establishment of unresponsiveness to self antigens of newly generated lymphocytes, due to a mechanism of central clonal deletion. We hypothesized that self-reactive lymphocytes causing autoimmune disease may be successfully eliminated by highly immunosuppressive yet not necessarily myeloablative conditioning in conjunction with allogeneic blood stem cell transplantation, since immunocompetent alloreactive lymphocytes of donor origin can effectively eliminate residual host-type hematopoietic cells, self-reactive lymphocytes included, by a mechanism that resembles graft-vs-leukemia (GVL) effects. The present report is an attempt to confirm the existence of graft-vs-autoimmunity (GVA) effects in parallel with amplification of the alloreactive potential of donor lymphocytes following allogeneic non-myeloablative stem cell transplantation (NST). methods: We identified a patient with severe psoriatic arthritis who also had philadelphia (bcr/abl) positive chronic myelogenous leukemia and therefore was fully eligible for NST. Both diseases responded initially to non-myeloablative conditioning involving fludarabine 30 mg/m2 x 6, anti-T-lymphocyte globulin 10 mg/kg X 4, and busulfan 4 mg/kg x 2. RESULTS: The initial NST procedure was uneventful and resulted in elimination of all signs of autoimmunity (psoriasis and arthritis). recurrence of polyarthritis and exacerbation of psoriasis were observed in parallel with a significant increase in the proportion of male (host) dna, and 5% of the mitoses were bcr/abl positive, indicating an increase in the clone of CML. Both bcr/abl-positive cells identified by RT-PCR and psoriatic arthritis were successfully eliminated following discontinuation of anti-GVHD prophylaxis with cyclosporine A (CSA), which resulted in activation of the alloreactive potential of donor T cells, accompanied by graft-vs-host disease (GVHD), suggesting the existence of GVA effects. RT-PCR for bcr/abl remains consistently negative for nearly 3 years, and all dna remains donor type. CONCLUSIONS: The response of autoimmune disease manifestations to GVA effects in parallel with elimination of all host-derived hematopoietic cells supports our working hypothesis that autoimmune diseases caused by self-reactive lymphocytes may be effectively treated by elimination of alloreactive self-reactive lymphocytes following induction of host-vs-graft tolerance, in analogy with replacement of malignant or genetically abnormal host cells following DLI. It is therefore suggested that intentional GVA effects may be inducible by DLI following a conventional or preferably safer non-myeloablative regimen in recipients with life-threatening autoimmune diseases resistant to conventional modalities. Adoptive immunotherapy of autoimmunity may thus involve a two-step procedure: first, inducing host-vs-graft and graft-vs-host transplantation tolerance through a transient stage of mixed chimerism; second, inducing controlled GVA effects, initially by discontinuation of CSA and then, if indicated, by late outpatient DLI to eradicate residual hematopoietic cells of host origin.
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2/9. Will mixed chimerism cure autoimmune diseases after a nonmyeloablative stem cell transplant?

    BACKGROUND: Mixed chimerism after allogeneic bone marrow transplantation has been shown to cure a number of genetic disorders in both the clinical and experimental settings. Although encouraging results have been reported from animal experiments, the role of mixed chimerism in eliminating autoimmune disorders is not clear. methods: A 50-year-old man with extensive psoriasis received an allogeneic transplant from his brother after nonmyeloablative conditioning with fludarabine, melphalan, and Campath-1H for relapsed non-Hodgkin's lymphoma. The chimerism status and the immunological recovery after the transplant were serially monitored. RESULTS: Twenty-one months after the transplant, the patient continues to be in complete remission from psoriasis and lymphoma with stable mixed chimerism (30% to 40% donor cells), despite significant recovery of T-cell subsets and antigen-specific response. CONCLUSIONS: If mixed chimerism can be achieved safely with novel low-intensity conditioning regimens and results in sustained remission of autoimmune diseases, allogeneic transplantation may become a realistic therapy in the management of some patients with autoimmune disease.
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3/9. Recalcitrant psoriasis vulgaris associated with Laurence-moon-Biedl syndrome.

    We report a 30-year-old European (Ashkenazi Jewish) male with Laurence-moon-Biedl syndrome (Bardet-Biedl type) who was hospitalized because of severe recalcitrant plaque-type psoriasis. Laurence-moon-Biedl syndrome has been shown to be linked to the chromosome 11q region in the majority of the patients of European descent. The same 11q region had increased frequency of aberrations in the study that included cytogenetic analysis of 477 psoriatic patients. The animal model of the syndrome (mice) showed abnormalities in hair growth and epidermal differentiation. This genetic association between Laurence-moon-Biedl syndrome and psoriasis can contribute to the understanding of the factors involved in the initiation of psoriasis and factors that modulate its severity and resistance to therapy.
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4/9. Generalized pustular psoriasis complicated by acute respiratory distress syndrome.

    psoriasis has a chronic and relatively benign course. However, severe complications are possible. One rare complication is acute interstitial pneumonitis. This entity should be suspected when a patient presents with dyspnoea and high fever. knowledge of this pathology is crucial, for although it is essential to rule out aetiologies requiring specific management such as microbial infection or drug-related syndromes, diagnosis should not be delayed as its severe clinical course is improved by corticosteroids. We report two patients with an acute respiratory distress syndrome arising during the course of pustular psoriasis. Repeated bacteriological testing in lungs and blood remained negative. In both cases lung involvement was severe, requiring artificial ventilation. Dramatic clinical resolution was obtained by using corticosteroids. Besides infectious causes and drug hypersensitivity to methotrexate or acitretin, acute respiratory distress syndrome, sometimes due to a pulmonary capillary leak syndrome, is a rare cause of pneumonitis in the course of psoriasis, and may be fatal. Its pathogenesis is unknown. However, animal models suggest a role for T-helper (Th) 1 lymphocytes, known to be activated in psoriasis, and a role for tumour necrosis factor-alpha, a major Th1 cytokine, in alveolar damage.
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5/9. Resolution of immune-mediated diseases following allogeneic bone marrow transplantation for leukaemia.

    Experimental work in animal models suggests that the course of systemic and organ-specific autoimmune disorders can be modified by allogeneic bone marrow transplantation (BMT). We describe two patients, each with a long history of psoriasis and ulcerative colitis, who received an allogeneic BMT for leukaemia. Four years post-BMT, they remain in full remission of psoriasis and ulcerative colitis, and of their leukaemia. We review the evidence for support of the concept that both psoriasis and ulcerative colitis are immune-mediated disorders and speculate on the possible role of allogeneic BMT in treating life-threatening autoimmune disorders.
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6/9. Treatment of psoriasis vulgaris with a synthetic metalloporphyrin and UVA light.

    Sn-protoporphyrin is a synthetic heme analogue which inhibits the catabolism of natural heme to bilirubin and can suppress a wide variety of experimentally induced or naturally occurring forms of jaundice in animals and man. Ten patients, 9 of whom were substantially or completely unresponsive to other forms of therapy, received 2.0 mumol/kg body weight of Sn-protoporphyrin on day 0 of this study followed by UVA light treatment for 21 days. Severity of psoriatic plaques, clinically scored (erythema 0-3; scaling, 0-3; infiltration, 0-3;) declined from a mean /- score of 7 /- 0.3 on day 0 to 3.6 /- 0.7 on day 21. Psoriatic lesions were improved in all patients and in some the effect was dramatic. No deleterious side effects were registered. As shown in this study, one-day treatment with Sn-protoporphyrin followed by conventional UVA light treatment may be a useful therapeutic modality for psoriasis patients and merits further investigation.
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7/9. methotrexate osteopathy in long-term, low-dose methotrexate treatment for psoriasis and rheumatoid arthritis.

    BACKGROUND: In dermatology and rheumatology, methotrexate is frequently prescribed in low dosages per week; in oncology, high dosages per week are prescribed. methotrexate osteopathy was first reported in children with leukemia treated with high doses of methotrexate. In animal studies, low doses of methotrexate proved to have an adverse effect on bone metabolism, especially on osteoblast activity. OBSERVATIONS: methotrexate osteopathy is a relatively unknown complication of low-dose methotrexate treatment. We describe three patients treated with low-dose oral methotrexate in whom signs and symptoms were present that were similar to those found in children treated with high doses of methotrexate. All three patients had a triad of severe pain localized in the distal tibiae, osteoporosis, and compression fractures of the distal tibia, which could be identified with radiographs, technetium Tc 99m scanning, and magnetic resonance imaging. CONCLUSIONS: methotrexate osteopathy can occur in patients treated with low doses of methotrexate, even over a short period of time. As pain is localized in the distal tibia, it is easily misdiagnosed as psoriatic arthritis of the ankle, but the diagnosis can be correctly made by careful investigation and use of imaging techniques. The only therapy is withdrawal of methotrexate. It is important that more physicians become aware of this side effect of methotrexate therapy, which can occur along with arthritic symptoms.
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8/9. Development of psoriasis after syngeneic bone marrow transplant from psoriatic donor: further evidence for adoptive autoimmunity.

    Transfer of donor immunity has been demonstrated in animal models of both allogeneic and syngeneic bone marrow transplantation (BMT). Clinical case reports have suggested that human autoimmune disease may be similarly transferred. However, it is difficult to completely exclude autoimmune phenomena associated with graft-versus-host disease (GVHD) as previously reported cases are of allogeneic BMT. In addition, the onset of autoimmunity has been distantly related to the timing of the transplant, perhaps because of the immunosuppression used for prophylaxis and treatment of GVHD. We describe a patient in whom the development of psoriasis shortly after receiving syngeneic bone marrow from a psoriatic donor and its recurrence with arthropathy following a second syngeneic BMT provide more direct evidence for the adoptive transfer of human autoimmune disease, probably by T cells.
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9/9. Outcome of rheumatoid arthritis and psoriasis following autologous stem cell transplantation for hematologic malignancy.

    Based on successful results in animal models, it has been proposed that high-dose myeloablative therapy followed by autologous bone marrow or stem cell transplantation (ABMT/ASCT) may cure autoimmune disease. The coexistence of autoimmune disease and hematologic malignancy provides an opportunity to examine the response of autoimmune disease to ABMT or ASCT. We describe 4 patients with autoimmune disease (3 with psoriasis and 1 with rheumatoid arthritis) and hematologic malignancy. In each patient, the autoimmune disease remitted posttransplantation, but, in 4 patients with long-term followup, it recurred at 8-24 months. The earliest relapse occurred in a patient treated with interferon-alpha. Our experience suggests that a single autograft with unpurged stem cells is unlikely to cure autoimmune disease, but that other strategies building on this approach are worthy of investigation.
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