Henry H. Roenigk

Methotrexate in psoriasis: Revised guidelines

The decision to administer methotrexate for the t reatment of psoriasis should be individualized. Each patient should be evaluated with reference to disease severity, amount of discomfort, degree of incapacity, and general medical and psychologic condition. Methotrexate is indicated in the symptomatic control of recalcitrant psoriasis not responsive to topical therapy. The diagnosis of psoriasis and the need for methotrexate therapy should be established by dermatologic consultation. In general, these patients should have severe psoriasis that m a y be life-ruining physically, emotionally, or economically. The psoriasis should be so severe that it cannot be adequately controlled by standard topical antipsoriasis therapy. Some examples of candidates for methotrexate therapy are patients with the following:

Treatment of mycosis fungoides with photochemotherapy (PUVA): Long-term follow-up

BACKGROUND Mycosis fungoides (MF) is a non-Hodgkins T-cell lymphoma of the skin that often begins as limited patches and plaques with slow progression to systemic involvement. No studies have been published comparing photochemotherapy (PUVA) with other topical therapies in the treatment of early-stage disease. OBJECTIVE The purpose of the study was to examine our long-term experience using PUVA to treat early-stage MF and to compare its effectiveness and side-effect profile with other previously reported topical therapies. METHODS Eighty-two patients with MF (83% stage IA or IB) were treated with PUVA. Clinical and histologic features were observed for a period from 2 months to 15 years (median, 43 months). RESULTS A response was noted in 78 patients (95%) with complete clinical and histologic clearing in 53 patients (65%) for all stages. The mean duration of total complete response to PUVA for all stages was 43 months (3.6 years). The mean survival of our study group for all stages was 8.5 years. Signs of chronic actinic skin damage were found in 10% of patients, including three patients with basal cell carcinomas and three patients with squamous cell carcinomas. In a nonrandomized comparison with previously reported data for other topical therapies, the efficacy and side-effect profile of PUVA compared favorably. CONCLUSION PUVA is an effective and safe therapy for MF with prolonged disease-free remissions being achieved. Patients with stage I and II MF respond best to PUVA. Palliative therapy with PUVA is useful in more advanced cases of MF.

Effects of topically applied capsaicin on moderate and severe psoriasis vulgaris

Alterations in the cutaneous vascular system are prominent in psoriasis and may play an important role in the pathogenesis of this disorder. We evaluated the effects of topically applied capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide), a known inhibitor of cutaneous vasodilatation, on moderate and severe psoriasis. Under a double-blind paradigm, forty-four patients with symmetrically distributed psoriatic lesions applied topical capsaicin to one side of their body and identical-appearing vehicle to the other side for 6 weeks. After 3 and 6 weeks of treatment, we performed ratings on changes in scaling and erythema, as well as overall improvement of the psoriasis. Over the course of the study, significantly greater overall improvement was observed on sides treated with capsaicin compared to sides treated with vehicle. Similarly, significantly greater reductions in scaling and erythema accompanied capsaicin application. Burning, stinging, itching, and redness of the skin were noted by nearly half of the patients on initial applications of study medication but diminished or vanished upon continued application. These results suggest that topical application of capsaicin may be a useful new approach in the treatment of psoriasis.

The cutaneous mucinoses

The cutaneous mucinoses are a group of connective tissue disorders characterized by the deposition of mucin, either focally or diffusely, in the interstices of the dermis. The diseases may be a primary (metabolic) or secondary (catabolic) process. Systemic abnormalities are seen with most of these disorders. This review discusses the primary mucinoses in which the predominant dermal mucin is hyaluronic acid. Current therapy and proposed mechanisms for the mucinoses are considered.

Effectiveness of interferon alfa-2a combined with phototherapy for mycosis fungoides and the Sézary syndrome.

PURPOSE To investigate the efficacy of combined topical therapy and systemic interferon alfa-2a in patients with mycosis fungoides (MF) and the Sézary syndrome (SS). PATIENTS AND METHODS Between December 1987 and April 1993, 39 patients with all stages of MF and SS were treated with combined phototherapy and systemic interferon alfa-2a as part of two institutional studies. The initial phase I study of 15 patients established the maximum-tolerated dose of interferon and has been previously reported. Subsequently, 24 patients have been entered onto a phase II trial. Long-term follow-up data are provided for both studies. RESULTS The median follow-up duration for the entire cohort is 28 months. Patients with all stages of disease were enrolled (stage IB, n = 14; IIA, n = 5; IIB, n = 6; III, n = 8; IVA, n = 5; IVB, n = 1). Thirty-four patients had received previous therapy. Overall, 36 of 39 patients achieved a complete response (CR; 62%) or partial response (28%) to therapy. The median response duration is 28 months (range, 1 to 64). Twenty-nine of 39 patients are alive, with a median survival duration of 62 months (range, 1 to 66). CONCLUSION Interferon alfa-2a combined with phototherapy is an effective, safe, durable therapy for MF and SS.

Atypical keloids after dermabrasion of patients taking isotretinoin

Six patients underwent dermabrasion while on or having recently completed isotretinoin (Accutane) therapy. All patients developed keloids in atypical locations; the keloids eventually responded to topical or intralesional steroid therapy. Retinoids have a modulatory effect on connective tissue metabolism, including suppression of collagenase, which may enhance keloid formation. Dermabrasion should be delayed in those patients taking or recently on isotretinoin therapy.

Mycosis fungoides and the Sézary syndrome: a review of pathogenesis, diagnosis, and therapy.

Mycosis fungoides (MF) and the Sézary syndrome (SS) are non-Hodgkins lymphomas with a T-cell phenotype, which have cutaneous involvement as their predominant feature. These disorders are becoming more common, and the patients are frequently being referred to medical oncologists for assistance in management. The development of advanced laboratory techniques, such as molecular genetics and cell-surface phenotyping, has greatly enhanced our understanding of their pathogenesis and may lead to identification of responsible etiologic factors. A myriad of treatment options have been investigated including topical approaches, systemic chemotherapy, and external radiation. Currently, extensive trials are underway examining the potential benefits of agents such as the interferons, interleukin-2, monoclonal antibodies, the retinoids, 2-chlorodeoxyadenosine, and other novel biologic response modifiers or chemotherapeutics. Although all these therapies have benefit in phase II trials, few randomized comparative trials have been performed to identify optimal therapies. Performance of such trials should now become a priority.

Dermatologic surgery : principles and practice

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Photochemotherapy in cutaneous T cell lymphoma and parapsoriasis en plaques: Long-term follow-up in forty-three patients

Forty-three patients with clinical plaque- and tumor-stage mycosis fungoides, the erythrodermic/Sézary syndrome variant of mycosis fungoides, and parapsoriasis en plaques were treated with oral psoralens and ultraviolet A (PUVA). Pretreatment skin biopsies, evaluated by light microscopy, revealed seventeen diagnostic, seventeen suggestive, and nine nonspecific specimens. Clinical and histologic parameters were followed for an average of 38.4 months (range, 4-67 months). Twenty-five patients had complete clearing, and fourteen did not respond. Most patients in the complete-response group had either plaque lesions of mycosis fungoides or parapsoriasis en plaques prior to PUVA. Most patients in the no-response group had either tumor lesions or the erythrodermic/Sézary mycosis fungoides at the start of PUVA. In the no-response group the treatment modalities used prior to PUVA were twice the number used in the complete-response group. Patients in the complete-response group had clearing of their lesions after an average PUVA dose of 117 joules/cm2. Relapse occurred in seventeen patients after an average remission time of 6.3 months and responded to additional PUVA. Patients whose skin remained clear after the first course of PUVA continued to have clear skin for up to 58 months, with an average complete remission of 29.5 months by the end of the study period. Histologic evaluation before PUVA and at clearing revealed a definite trend toward a normal microscopic picture, but at least a mild inflammatory infiltrate usually persisted. At the end of the study period, the lesions of ten patients had entirely cleared for an average of 44 months, the lesions of five had cleared during a second course of PUVA, five had stable limited-plaque disease while receiving maintenance PUVA, eleven were undergoing electron beam radiation therapy or chemotherapy for progressive disease, ten had died, and two patients were lost to follow-up. Therefore, in the early stage of mycosis fungoides, PUVA may induce significant disease-free intervals. Prior treatment with a variety of modalities, the patients age, and/or the duration of disease may affect response to PUVA.

Treatment of resistant severe psoriasis with systemic cyclosporine

Four patients with severe psoriasis have been treated with oral cyclosporine for 6 months. Two had generalized erythroderma and two had extensive plaque-type psoriasis; all had either become unresponsive to or were unable to use other accepted treatments. All four patients responded rapidly and were completely clear of psoriasis within 3 weeks of beginning therapy. Initial doses ranged from 7.5 to 8.5 mg/kg/day. Mild reversible nephrotoxicity occurred in the one patient whose cyclosporine trough level briefly exceeded 200 ng/ml. Cyclosporine may offer an alternative therapeutic modality in the management of erythrodermic or severe resistant plaque-type psoriasis. The effectiveness of cyclosporine in psoriasis underscores the putative role of cell-mediated immune factors in the pathogenesis of psoriasis.