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Biomedical subjects

J Guitart

Publications and source records attributed to J Guitart.

At least 37 records · Page 2Linked to original sources

Cutaneous CD8 T cell infiltrates in advanced HIV infection.

BACKGROUND: Aggressive non-Hodgkin's lymphomas are common among patients infected with HIV. Although such lymphomas are mostly of the B-cell type, various cases of cutaneous T-cell lymphoma (CTCL) have also been reported. Recent reports suggest that some HIV-related lymphoproliferative conditions may not be clonal processes, but polyclonal lymphoid proliferations. OBJECTIVE: We reviewed our experience with HIV patients seen at the dermatology clinics for possible CTCL. METHODS: A retrospective study was performed to evaluate clinical, laboratory, and histologic findings of HIV-infected patients with atypical T-cell cutaneous infiltrates. RESULTS: We observed 9 patients with advanced HIV infection and a cutaneous eruption characterized by a dense infiltrate of lymphocytes resembling mycosis fungoides histopathologically, but composed of CD8(+) cells. Although clonality was not identified in any of the 6 cases tested, 3 patients had similar CD8(+) infiltrates involving lymph nodes or bone marrow. Of the 9 patients, 8 died of AIDS wasting syndrome or infections in less than 1 year. CONCLUSION: Cutaneous and systemic infiltrates with polyclonal CD8 T lymphocytes can be seen in patients with advanced HIV infection and profound CD4 lymphopenia. The clinical presentation may resemble CTCL and is associated with a poor outcome.

Adult↗

Pleomorphic T-cell infiltrate associated with molluscum contagiosum.

The authors observed a pleomorphic lymphocytic infiltrate composed of CD8 cytotoxic/suppressor T-cells in two pediatric cases associated with molluscum contagiosum. T-cell clonality was not detected. In both cases, the lesions resolved after the biopsy was performed. The patients were otherwise healthy, and no evidence of lymphoproliferative process was detected on follow-up. The authors believe the pleomorphic lymphoid infiltrate is inflammatory and reactive in nature. The close apposition of lymphocytes to molluscum bodies and cytoid bodies with high expression of CD30 and the proliferating marker Ki67 is suggestive of a cytotoxic cell-mediate blastic reaction against poxvirus antigens.

Antigens, CD20↗

O6-alkylguanine-DNA alkyltransferase in cutaneous T-cell lymphoma: implications for treatment with alkylating agents.

Mycosis fungoides is a low-grade cutaneous T-cell lymphoma. Early treatment often involves the use of topical chemotherapy such as mechlorethamine or carmustine although single-agent oral chemotherapy with alkylators is common for advanced disease. Recently, in a Phase I study of the new alkylating agent temozolomide, two mycosis fungoides patients experienced a complete response. The mechanism of resistance to alkylating drugs such as temozolomide is thought to be due to the presence in tumor cells of the DNA repair protein, O6-alkylguanine-DNA alkyltransferase (AGT). The protein mediates a reaction with the O6-position of guanine in DNA, removing the lesion and leaving guanine intact. We, therefore, examined the levels of AGT in CD4+ T lymphocytes obtained by negative antibody selection from the blood of noncancerous individuals and mycosis fungoides patients, and in paraffin-embedded sections from mycosis fungoides patch, plaque, or tumor lesions and cells from involved lymph nodes. AGT protein levels were measured by quantitative immunofluorescence microscopy using a monoclonal antibody against human AGT. Using this approach, the mean level of our positive control (AGT-expressing cells) was 84,807 molecules/nucleus; values below 5,000 molecules/nucleus are considered very low. The mean AGT level in CD4+ T lymphocytes from noncancerous and cancerous individuals was 18,618 (n = 12) and 8,593 (n = 5), respectively. The mean fraction of outliers in circulating CD4+ T lymphocytes from mycosis fungoides patients was statistically significantly lower than T cells in lymph nodes. AGT molecules/nucleus from lymph node biopsies from 8 of 10 patients showed low (< 10,000 molecules/nucleus) or undetectable levels (n = 5) of AGT. The mean AGT level from samples of mycosis fungoides patch/plaque and tumor was also low at 221 (n = 4) and 2,363 (n = 6), respectively. Surprisingly, Hut78, a mycosis fungoides T-cell lymphoma cell line, was positive for AGT activity (median: 77,700 molecules/nucleus), and Hut102--another mycosis fungoides cell line--was low (median: 5,990 molecules/nucleus). Because AGT is a primary means of cell resistance to alkylating agents, the low level of AGT in neoplastic T lymphocytes from patients with mycosis fungoides suggests that treatment with alkylating agents producing O6-alkylguanine adducts, such as carmustine or temozolomide, may produce improved clinical outcomes.

Adult↗

Preferential activation of the complement system in the lower epidermis of patients with pemphigus vulgaris.

Pemphigus vulgaris (PV) is an immune-mediated blistering skin disease characterized by acantholysis of the suprabasal epidermis and by IgG autoantibodies targeting a desmosomal component, desmoglein 3. IgG alone has been demonstrated to induce acantholysis in some experimental conditions. The role of the complement system in blister formation in PV remains controversial. We describe four consecutive patients with new-onset PV. The acantholytic process occurred in the lower epidermis and colocalized with deposition of complement C3 and the membrane attack complex C5b-9. The colocalization of complement deposition with the acantholytic process in the lower epidermis supports a role for the complement system in blister formation in PV.

Adult↗

Skin as the primary site of Hodgkin's disease: a case report of primary cutaneous Hodgkin's disease and review of its relationship with non-Hodgkin's lymphoma.

We report an elderly patient who presented with a single cutaneous nodule of primary cutaneous Hodgkin's disease (PCHD). Reed-Sternberg cells, expressing CD30 and CD15, but not leukocyte common antigen (CD45RB), were identified in the neoplastic cells. Southern blot analysis failed to detect T-cell receptor or immunoglobulin gene rearrangement. A work-up for systemic disease at the time of presentation was negative, supporting the diagnosis of PCHD. Nevertheless, 1 year later, the disease course was complicated by the development of nodal HD and nonHodgkin's lymphoma (NHL). This case report supports the existence of this rare, but distinct, cutaneous tumor.

Aged↗

Fatal cytophagic histiocytic panniculitis after a short response to cyclosporine.

Cytophagic histiocytic panniculitis (CHP) is a disorder characterized by a histiocytic infiltrate in the subcutaneous adipose tissue which often extends to involve systemic organs. Fever, pancytopenia, hepatosplenomegaly, mucosal ulcers and serositis are common systemic symptoms. Although remissions have been reported, the disease tends to follow a chronic course often complicated by terminal hemorrhagic diathesis and death. Several reports in the recent literature have suggested that cyclosporine is the treatment of choice in CHP. We report the first case of cyclosporine treatment failure in CPH. Despite an initial response to treatment and persistent resolution of cutaneous lesions, the internal disease progressed resulting in the patient's death. Therefore the evolution of skin lesions and signs of systemic involvement may not be an accurate assessment of disease activity in patients with CHP being treated with cyclosporine.

Cyclosporine↗

Lichenoid changes in mycosis fungoides.

BACKGROUND: The lichenoid tissue reaction (LTR) is present in a variety of dermatoses. Numerous histologic variants of mycosis fungoides (MF) have also been described. OBJECTIVE: Our purpose was to analyze a subset of patients with mycosis fungoides (MF) who had a prominent LTR at the time of presentation. METHODS: Clinical and pathologic features were evaluated in 12 patients with MF and an LTR. RESULTS: The primary complaint was intense pruritus (in 10 of 12 patients). An accelerated course was noted in one half of the patients including four with Sézary syndrome. Four patients died: two with Sézary syndrome and two with extensive patch/plaque MF. Lymphocyte atypia, prominent basal cell layer epidermotropism, and the presence of plasma cells and eosinophils may help to distinguish lichenoid MF from lichen planus. CONCLUSION: A subset of patients with MF present with lichenoid changes. The pathologic features may have a striking resemblance to lichen planus. Our findings suggest that lichenoid changes in MF tend to be associated with intense pruritus and may connote a poor prognosis.

Adult↗

Solitary cutaneous myofibromas in adults: report of six cases and discussion of differential diagnosis.

Six solitary, dermal or subcutaneous lesions occurring in adult patients are presented. These masses had a circumscribed, lobulated configuration; they were composed of fusiform and epithelioid cells that lacked atypical nuclear features. The pattern of growth featured fascicles and nests, a myxofibrous stroma, and prominent blood vessels with a focally "hemangiopericytoid" appearance. Immunohistochemical analyses showed uniform reactivity for vimentin and alpha isoform-actin, with negativity for desmin and neural determinants. The overall appearance of the lesions was similar to that of "infantile myofibromatosis," and corresponded to previous descriptions of "solitary myofibroma(tosis)" in adults. Immunophenotypic and ultrastructural support exists for a proposed myofibroblastic nature for such proliferations. Differential diagnostic considerations include neurothekeomas, plexiform fibrous histiocytomas, nodular fasciitis, cutaneous inflammatory pseudotumors, dermatomyofibromas, leiomyomas, and other forms of fibromatosis affecting the skin and superficial soft tissues.

Adult↗

Hand-foot syndrome associated with liposome-encapsulated doxorubicin therapy.

BACKGROUND: Acquired immune deficiency syndrome (AIDS)-related Kaposi's sarcoma (KS) is a common complication of patients infected with human immunodeficiency virus and can cause significant morbidity. Long term therapy with standard chemotherapeutic regimens has been limited by relatively short durations of response and potential toxicity. Once therapy is discontinued, the disease typically progresses. Liposome-encapsulated doxorubicin (DOX-SL) currently is being evaluated for treating patients with AIDS-related KS. Early reports suggest a high response rate and good patient tolerance permitting continued therapy for extended periods. METHODS: Patients with AIDS-related KS are treated with a DOX-SL regimen every 2-3 weeks and are followed carefully for evidence of adverse treatment effects. RESULTS: Two cases of hand-foot syndrome (HFS) in patients receiving DOX-SL for AIDS-related KS are reported. Tissue studies demonstrated changes consistent with a toxic effect of the drug on keratinocytes. Hand-foot syndrome was reversible once treatment stopped; however, treatment cessation resulted in primary disease recurrence. CONCLUSIONS: Hand-foot syndrome can be debilitating and may be a limiting factor in the prolonged use of DOX-SL for AIDS-related KS for some patients. It is critical for clinicians using this drug to identify this side effect to limit HFS-associated morbidity.

Acquired Immunodeficiency Syndrome↗

Intertrigo: a practical approach.

Although the precise diagnosis of intertriginous dermatosis is hampered by the unique conditions of the skin folds, there are a few common rules to be considered in the therapeutic approach. Dryness must be reached by changing occlusive conditions, astringent compresses, and absorbing powders. To improve the primary dermatosis, superimposed infection must be treated. With rare exceptions, fluorinated steroids should not be used in occlusive areas. Finally, the skills of a dermatologist may be required to optimize the care of patients with complex dermatoses involving the flexural skin.

Algorithms↗