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BACKGROUND: Idiopathic CD4+ T lymphocytopenia is defined as a CD4+ T lymphocytopenia of less than 0.3X109/L that is not associated with human immunodeficiency virus, other immunodeficiency, or immunosuppressive therapy. The associated clinical course and laboratory findings are variable. We describe a subset of patients whose peripheral CD4+ T-lymphocytopenia was transient, and suggest a pathomechanism for this phenomenon. OBSERVATIONS: We describe three patients with cutaneous T-cell lymphoma, atopic dermatitis, or psoriasis in whom acute erythroderma was concomitant with a peripheral CD4+ T lymphocytopenia that normalized after resolution of the erythroderma. Immunoperoxidase staining of skin biopsy specimens and quantitative estimation of CD4+ T lymphocytes in the cutane- ous and peripheral blood compartments demonstrated that the peripheral CD4+ T lymphocytopenia in these cases most probably resulted from sequestration of CD4+ T lymphocytes in the skin. The skin of an erythrodermic patient appears capable of sequestering 1010 to 1011 CD4+ T lymphocytes, whereas the peripheral blood compartment contains in the range of 109 CD4+ T lymphocytes. CONCLUSIONS: We propose that CD4+ T lymphocytopenia can occur as a result of acute erythroderma of multiple causes and that acute erythroderma associated with transient CD4+ T lymphocytopenia be considered as an exclusion criterion for idiopathic peripheral blood CD4+ T lymphocytopenia.(Arch Dermatol. 1994;130:1530-1533)

• BACKGROUND.— Paraneoplastic pemphigus refers to a specific disease entity in which neoplasia is associated with severe mucosal ulceration and polymorphous cutaneous eruptions, sometimes resembling erythema multiforme. Direct immunofluorescence and indirect immunofluorescence on standard substrates are similar to pemphigus vulgaris; however, paraneoplastic pemphigus serum uniquely binds to all epithelia and has distinctive immunoprecipitation characteristics. OBSERVATIONS.— A 63-year-old woman with chronic lymphocytic leukemia developed a severe, mucocutaneous, vesiculobullous eruption with the clinical and histopathologic characteristics of lichen planus pemphigoides evolving into a Stevens-Johnson—like presentation and the immunofluorescence findings of pemphigus vulgaris. Evaluation of her serum confirmed the presence of autoantibodies specific for paraneoplastic pemphigus by indirect immunofluorescence and immunoprecipitation criteria. CONCLUSION.— The spectrum of paraneoplastic pemphigus must now be expanded to include cases that present clinically and histologically as a lichen planus pemphigoides— like eruption.(Arch Dermatol. 1993;129:866-869)

• BACKGROUND AND DESIGN.— The optimal therapy for the mycosis fungoides type of cutaneous T-cell lymphoma has yet to be determined. Based on recent reports on the efficacy of high-dose interferon alfa in cutaneous T-cell lymphoma, we chose to test the hypothesis that systemic adjunctive therapy with low-dose interferon alfa along with psoralen and long-wave UV-A radiation (PUVA) could decrease the amount of PUVA necessary to achieve the best response, as well as improve the therapeutic effect of PUVA. Five patients with cutaneous T-cell lymphoma (mycosis fungoides type) were initially treated unsuccessfully with PUVA alone (three times a week for at least 3 months); PUVA was stopped, patients' diseases were restaged, then interferon alfa (3×106 U/d for 1 week, then 6×106 U/d for 1 week) was initiated 2 weeks prior to restarting PUVA. Responses to treatment were graded as complete remission (skin clear, or negative biopsy specimens of remaining dermatitic lesions), partial remission (>50% improvement), progression (>25% worsening), or no change (failure to qualify for other categories) at 4, 8, 12, and 16 weeks. OBSERVATIONS.— After 3 to 5 months of treatment with PUVA thrice weekly, none of the patients treated with PUVA alone had achieved complete remission. By contrast, systemic adjunctive therapy with low-dose interferon alfa along with PUVA resulted in complete remissions in all five (100%) patients in an average of 3.2 months (in three patients, lesions were cleared by 3 months). An average of 107 additional joules (68% more) and 1.6 additional months of PUVA administered thrice weekly was required to achieve the best response attainable with PUVA alone compared with complete remissions achieved with combined interferon alfa and PUVA therapy. CONCLUSION.— These data indicate that patients with disease refractory to PUVA alone can achieve a complete remission if they restart treatment with PUVA in combination with well-tolerated low doses of interferon alfa. In addition, the duration of PUVA exposure can be reduced with the addition of low-dose interferon alfa to the conventional PUVA treatment of cutaneous T-cell lymphoma of the mycosis fungoides type in such patients.(Arch Dermatol. 1993;129:747-752)

• BACKGROUND AND DESIGN.— There is much confusion in the clinical classification of immune-mediated subepithelial blistering diseases of mucous membranes. We conducted a 6-year comprehensive study to better classify this heterogeneous disease group. Indirect immunofluorescence was performed on a salt-split-skin substrate to detect circulating antibasement membrane antibodies (n=47). Serologic reactivity against cultured keratinocyte antigens was examined by immunoblots (n=38) and immunoprecipitation (n=15). The results were correlated with the clinical features and direct immunofluorescence data of the entire patient group (n=87) without preassignment of clinical diagnoses. χ2 Statistical analyses compared these results with those of the classic bullous pemphigoid group (n=36). RESULTS.— When compared with the bullous pemphigoid patients, a subset of patients with combined oral mucosal and skin lesions demonstrated marked similarity in direct and indirect immunofluorescence findings and in serologic reactivity to bullous pemphigoid antigens. By contrast, a subset of patients with only ocular lesions exhibited significantly lower in vivo deposits of IgG and C3, higher deposits of fibrin, virtual absence of circulating antibodies, and negative serologic reactivity to bullous pemphigoid antigens. CONCLUSIONS.— Ocular patients without skin or mouth lesions, in particular those with negative indirect immunofluorescence, should be distinctively classified as ocular cicatricial pemphigoid, a unique clinical and immunopathologic entity. Patients with mucous membrane involvement who also demonstrate skin lesions and antibodies to the roof of salt-split-skin substrate should be classified as anti-BP Ag mucosal pemphigoid, even though they may exhibit severe oral and/or ocular diseases. The remaining mucous membrane patients are heterogeneous. Some can be classified on the basis of autoantibodies to other basement membrane determinants, or if serum autoantibody negative, on the basis of clinical features (ie, pure oral mucosal pemphigoid or overlapping mucosal involvement).(Arch Dermatol. 1993;129:448-455)

• BACKGROUND AND DESIGN.— T-cell activation appears to be critical for the maintenance of psoriatic lesions. In this study, we determined whether cytokines released by epidermal cells from psoriatic lesions are providing signals that result in propagation of intralesional T-cell activation. Supernatants were obtained from epidermal cell cultures derived from skin biopsy specimens of psoriatic patients and normal subjects. These supernatants were added to purified normal CD4+ T cells activated via T-cell receptor (immobilized anti-CD3 and fibronectin) or via other activating pathways (anti-CDw60 or UM4D4). RESULTS.— Psoriatic supernatants (n=9), but not normal supernatants (n=7, P<.0006), potentiated T-cell stimulation with anti-CD3 and fibronectin to 172%±41% over control stimulation levels. The degree of lesional psoriatic epidermal cell potentiation correlated with the clinical severity of the lesion (r=.82, P=.007). Psoriatic epidermal cytokine potentiation of T-cell activation was not limited to T-cell receptor mediated stimulation; potentiation of anti-CDw60— stimulated CD4+ T cells was also observed. Neutralizing antisera to interleukin 1 and interleukin 8, but not interleukin 6, were found to reduce only partly the observed potentiation of T-cell activation. To determine whether cyclosporine is down modulating T-cell-potentiating cytokine activity in psoriasis, we compared samples obtained during a doubleblind clinical trial of intralesional cyclosporine. T-cell— potentiating activity from psoriatic lesional sites treated with cyclosporine was not significantly modulated relative to the activity derived from vehicle-treated or untreated sites. CONCLUSION.— These data demonstrate that lesional psoriatic epidermal cells release a balance of cytokines that potentiate T-cell activation. Because normal epidermal cells do not potentiate T-cell activation in this system, these findings demonstrate a mechanism by which the epidermis may nonspecifically potentiate and perpetuate T-cell activation in psoriatic lesions.(Arch Dermatol. 1992;128:1479-1485)

• Cyclosporine is known to be effective in the treatment of psoriasis. In this study, we have used oral cyclosporine (6 mg/kg per day) given for 5 to 30 weeks to 24 patients for the treatment of 12 different dermatoses. Patients with the following diseases demonstrated a marked response or total clearing: 1 patient each with pyoderma gangrenosum, pityriasis lichenoides chronica, and psoriasis of the acrodermatitis continua of Hallopeau type. Moderate to marked response occurred in both patients with epidermolysis bullosa acquisita and the patient with hidradenitis suppurativa. Minimal to moderate responses were obtained in both patients with granuloma annulare, 1 of 2 with acrodermatitis continua of Hallopeau, both patients with Darier's disease, and 1 of 6 patients with vitiligo. Little or no response was noted in both patients with sarcoidosis, all 3 patients with pityriasis rubra pilaris, 5 of 6 patients with vitiligo, 1 patient with pemphigus foliaceous, and 1 with pemphigus vulgaris. Clinical side effects were mild and transient and included dysesthesia, fatigue, hypertrichosis, nausea, and flushing. The most frequent clinically significant abnormalities were hypertension and renal dysfunction, with all factors normalizing within 1 month of discontinuation of cyclosporine therapy.(Arch Dermatol. 1990;126:339-350)

BACKGROUND: Cutaneous T-cell lymphomas comprise a broad spectrum of neoplasia ranging from indolent to highly aggressive types. To determine subset lineage and malignant vs benign nature, morphologic analysis, immunophenotyping, and flow cytometry have been used. However, given the shortcomings of these methods, molecular genetic techniques, which take particular advantage of the clonal nature of malignancy, are now being applied to better characterize and diagnose these lymphomas. RESULTS: Each antigen-specific T cell and its clonal progeny has a unique rearrangement of its T-cell receptor gene such that it can recognize very specific antigenic epitopes. By visualizing these particular T-cell receptor gene rearrangements, Southern hybridization techniques and polymerase chain reaction amplification can detect clonal populations of T cells in the skin, blood, and lymph nodes of patients with T-cell leukemias and lymphomas. Clonal T-cell populations have also been found in cases of benign disorders such as lymphomatoid papulosis and pityriasis lichenoides et varioliformis acuta. Although these disorders usually have a benign outcome, they may represent dysplastic clonal lymphoid expansions with a high incidence of spontaneous regression. CONCLUSIONS: Molecular genetic techniques have added to our ability to diagnose, characterize, and monitor the course of T-cell lymphomas and leukemias. In addition, they may provide insight into the pathogenesis of certain benign disorders.(Arch Dermatol. 1993;129:1484-1490)

BACKGROUND: Immune-mediated subepidermal bullous dermatoses characterized by in vivo—bound linear IgG deposition at the cutaneous basement membrane zone include bullous pemphigoid, ocular cicatricial pemphigoid, anti—bullous pemphigoid antigen mucosal pemphigoid, anti—epiligrin mucosal pemphigoid, epidermolysis bullosa acquisita, and the bullous eruption of systemic lupus erythematosus. In this article, we describe a novel IgG-mediated bullous dermatosis. OBSERVATIONS: Clinically, a unique nonscarring dermatosis was characterized by the sudden onset of extensive bullae and erosions on mucous membrane and skin, resembling toxic epidermal necrolysis or pemphigus vulgaris. Histologically, the patient's skin lesion demonstrated neutrophilic papillary dermal infiltration and subepidermal blister formation, resembling dermatitis herpetiformis. Immunopathologically, there was linear IgG and C3 deposition at the skin basement membrane zone. The patient responded well to prednisone and azathioprine immunosuppression and has achieved a lasting remission without further therapy. Further immunologic investigations revealed that this unique dermatosis is distinct from all other known IgG-mediated subepidermal bullous dermatoses. CONCLUSIONS: This novel deep lamina lucida pemphigoid can be distinctly termed anti—p105 pemphigoid on the basis of antigenic specificity of the autoantibodies. Although this novel dermatosis resembles toxic epidermal necrolysis clinically, prudent use of diagnostic immunofluorescence studies can clearly delineate its immunologic nature. Prompt recognition of this unique dermatosis and timely initiation of appropriate immunosuppressive therapy could be life-saving for those patients suffering from this dermatosis.(Arch Dermatol. 1994;130:343-347)

• Eosinophilic fasciitis has been reported to precede hematologic malignant neoplasms such as myelomonocytic leukemia, lymphocytic leukemia, and Hodgkin's lymphoma. In this case study, eosinophilic fasciitis occurred concurrently with cutaneous T-cell lymphoma (mycosis fungoides). The clinical diagnosis of eosinophilic fasciitis was based on painful sclerodermatous lesions on the extremities and trunk without acrosclerosis. There was histologic confirmation with edema and lymphocytic inflammation in the superficial muscular fascia and dermis. Deposition of immune reactants was found in the fascia and dermis. In addition, peripheral eosinophilia and circulating immune complexes were detected. The diagnosis of cutaneous T-cell lymphoma (mycosis fungoides) was based on extensive erythematous cutaneous plaques, dermal and epidermal lymphocytic atypia, loss of pan-T-cell immunologic markers, and a cutaneous lesional T-cell receptor β-chain rearrangement by Southern blot analysis. Eosinophilic fasciitis may occur as a paraneoplastic syndrome associated with hematologic malignant neoplasms, including mycosis fungoides. Cytokines or lymphokines released by activated immunocytes, either malignant leukocytes or normal leukocytes reacting to malignant cells, may be responsible for the eosinophilia and sclerosis seen in these associated hematologic malignant neoplasms.(Arch Dermatol. 1991;127:862-865)

• Epidermolysis bullosa acquisita (EBA), rarely reported in childhood, is described in a 10-year-old black girl. The age of onset during infancy and the clinical appearance mimicked hereditary dystrophic epidermolysis bullosa. Epidermolysis bullosa acquisita was diagnosed by direct immunofluorescence of perilesional skin, indirect immunofluorescence on normal epithelium and saline-split skin, direct immunoelectron microscopy, and immunoblotting of the patient's serum sample against partially purified EBA antigen/carboxyl domain of type VII collagen. Differentiation of mechanobullous disease in children is critical in that significant clinical benefit may be achieved in EBA with prednisone and/or dapsone therapy. A search for associated immunologic abnormalities and HLA-DR typing may help our understanding of EBA.(Arch Dermatol. 1989;125:944-949)

• In an open trial, five patients with lamellar ichthyosis showed no response to four weeks of treatment with oral cyclosporine (cyclosporine A) (6 mg/kg/d). Histologic examination of lamellar ichthyosis revealed hyperkeratosis; psoriasiform acanthosis; dilated, tortuous capillaries; and a slight perivascular lymphocytic infiltrate. Immunofluorescence studies revealed, in the epidermis, normal numbers of T6+DR+ Langerhans' cells and an absence of T cells and intercellular adhesion molecule-1 expression. In the papillary dermis, there were prominent capillaries as detected by staining with anti-factor VIII-related antigen. The endothelial cells also expressed large amounts of HLA-DR and intercellular adhesion molecule-1, suggesting that they were activated. Only occasional Langerhans' cells were found in the dermis. Histologic and immunofluorescence findings were unchanged with cyclosporine therapy. The effects of cyclosporine on lamellar ichthyosis are contrasted with those reported for psoriasis. Since lamellar ichthyosis and psoriasis share similar features of epidermal hyperproliferation and the presence of activated, dilated, tortuous vessels, but differ in the lack of immunologic cellular activity, their contrasting response to cyclosporine suggests that the target of the action of cyclosporine is the immune system rather than the keratinocyte or the endothelium. However, other factors may have to be considered.(Arch Dermatol 1989;125:511-514)

• Cyclosporine, a potent immunosuppressive agent, has been successfully used in the treatment of several dermatologic conditions including psoriasis. However, the drug does have an array of toxic side effects that need to be carefully considered when determining the risk-benefit ratio for the treatment of skin disease. We present another potential adverse effect of cyclosporine, namely, a benign lymphocytic infiltrate. This eruption developed in a patient with psoriasis after only ten days of cyclosporine therapy. The exact mechanism by which cyclosporine induced the lymphocytic infiltrate is unknown, but it is postulated that cyclosporine caused an imbalance of T-cell regulatory systems, thus resulting in an expanded T-cell subpopulation and the clinical manifestation of erythematous papules and nodules.(Arch Dermatol 1988;124:1097-1100)

• A patient with severe cicatricial pemphigoid demonstrated both in vivo bound and circulating anti-basement membrane zone antibodies of the IgA and IgG classes. Complement component 3 (C3) was also deposited in the basement membrane zone of lesional skin as well as in normal-appearing buccal mucosa of the patient. However, C1q was absent, while granular deposits of two factors of the alternative complement activating pathway, properdin and properdin factor B, were present only in the basement membrane zone of lesional skin, but not in normal buccal mucosa. Deposition of alternative complement pathway reactants in the lesion suggests that complement activation by IgA was associated with lesion development. Western blot analysis of the patient's serum on electrophoresed cultured keratinocyte antigens identified two distinct sets of epidermal antigens. While IgG bound antigens of 230, 205, 140, and 90 kd, the patient's IgA antibodies bound a distinct set of antigens, 180 and 130 kd. The potential pathogenic role of IgA in cicatricial pemphigoid is discussed.(Arch Dermatol. 1990;126:1466-1468)

• In this article, we describe a patient with progressive localized scleroderma, who subsequently developed pemphigus vulgaris on the previously affected sclerodermatous skin, and on the oral mucosa, the nasal mucosa, the laryngeal mucosa, and the scalp. The coexistence of pemphigus vulgaris with localized scleroderma and the histopathologic documentation of pemphigus vulgaris arising on a sclerodermatous skin have not been previously reported. Whether this is a random association or an association based on common immunologic pathomechanisms in pemphigus and localized scleroderma may be important in understanding these diseases.(Arch Dermatol. 1989;125:1555-1557)