Angiomas subcutáneos múltiples asociados con el comienzo de la diabetes mellitus / Multiple subcutaneous angiolipomas associated with new-onset diabetes mellitus

Un hombre de raza hispana de 44 años con antecedentes de diabetes mellitus tipo 2 y de accidente cerebrovascular se presentó en el Departamento de Dermatología del Hospital Monte Sinaí por haber observado nódulos de crecimiento rápido en ambas piernas (espinillas). Aproximadamente, dos meses antes de la aparición de los nódulos, el paciente había sido diagnosticado de diabetes mellitus tipo 2 con hemoglobina A1c (Hb A1c) del 8,5 por ciento. El paciente estaba tomando metformina por vía oral, 500 mg tres veces al día en el momento de la presentación. Aparecieron 6 nódulos durante un período de varios días. Producían quemazón y dolor punzante en la deambulación. Durante un período de 6 meses los nódulos descendieron en tamaño y 2 desaparecieron totalmente. La resolución de los nódulos coincidió con el control de la diabetes del paciente demostrada por una Hb A1c de 5,5 por ciento. El paciente negó haber tenido un trauma en las zonas de los nódulos. También negó cualquier asociación con púrpura o equimosis en los nódulos. Los antecedentes médicos significativos eran un ictus con hemiparesia residual a los 42 años de edad. En los antecedentes familiares no había enfermedades familiares reseñables, excepto una tía que tenía diabetes mellitus tipo 2. El paciente no tomaba alcohol, no fumaba ni consumía drogas por vía intravenosa. En la exploración física se encontraron 6 masas redondeadas simétricas móviles, blandas, bien demarcadas, de 1 a 2 cm de diámetro y de color de piel en la parte anterior de ambas piernas. El paciente era obeso (índice de masa corporal 38,5). Las pruebas de laboratorio (aparte de la elevación incial de la Hb A1c), eran normales. Se extirpó una de las masas. Histopatológicamente, se demostraron características típicas de angiolipoma (Figura ! a,B). No se realizó el cariotipo del angiolipoma. Puesto que la escisión del angiolipoma produjo descamación con un resultado estético malo, se intentó administrar 5mg/ml de triamcinolona dentro de la lesión sin éxito (AU)

Immunopathogenesis of scleroderma--evolving concepts.

Scleroderma, or systemic sclerosis, is a connective tissue disease which may affect various organ systems including skin, lungs, gastrointestinal tract, cardiovascular system and kidneys. While the etiology is not clear, it is currently believed that scleroderma may represent an autoimmune response to an unknown antigen. In this regard, there is evidence that both humoral and cellular immunity may play roles. The pathophysiology is complex and consists of three major features: (1) vascular damage; (2) mononuclear cellular infiltrates; and (3) massive deposition of newly synthesized connective tissue, mainly collagen. The major pathologic features of scleroderma and the roles of humoral and cellular immunity in its pathogenesis are reviewed and summarized.

Current therapy of pemphigus vulgaris.

Pemphigus vulgaris (PV) is a potentially fatal autoimmune blistering disease of the skin and mucous membranes, characterized by flaccid bullae that rupture and leave erosions. Its treatment is challenging. Although the use of systemic corticosteroids remains the cornerstone of effective therapeutic regimens for PV, their prolonged administration may lead to serious side effects. It is therefore necessary, for many patients, to add immunosuppressive agents or use immunomodulatory procedures to achieve remission. This paper will summarize the treatments available for PV, while focusing on the most recently available therapeutic options.

Cutaneous granulomas masquerading as tuberculoid leprosy in a patient with congenital combined immunodeficiency.

Combined immunodeficiency disorders are characterized by abnormalities in cellular and humoral immunity. This classification includes common variable immunodeficiency (CVI), a primary immunodeficiency disorder characterized by hypogammaglobulinemia, recurrent bacterial infections, and significant T-cell abnormalities. Associated autoimmune diseases include rheumatoid arthritis, pernicious anemia, idiopathic thrombocytopenic purpura, and systemic lupus erythematous. Granulomatous lesions in lymphoid tissues, solid organs, and skin have been reported. We describe a patient with CVI who developed cutaneous granulomas with perineural invasion; to our knowledge, this is a previously undescribed feature.

Cutaneous polyarteritis nodosa after streptococcal necrotizing fasciitis.

Polyarteritis nodosa (PAN) is a necrotizing arteritis of small and medium-sized vessels. It may present with hypertension and/or renal insufficiency. Peripheral neuropathy, myopathy, joint pains, testicular pain, and ischemic myalgias may also be seen. Gastrointestinal involvement may lead to gangrene of the bowel, peritonitis, perforation, intra-abdominal hemorrhage, and pancreatitis. The cutaneous manifestations include tender subcutaneous nodules grouped along the course of superficial arteries of the lower extremities, with or without an overlying livedo reticularis. Although multisystem involvement is characteristic, sometimes only one organ or system may be involved. Associations with viral hepatitis (both B and C) and streptococcal infection have been established for PAN. Recurrent strep infections of the upper respiratory tract, streptococcal glomerulonephritis and rheumatic fever have previously been linked to PAN. This report extends the spectrum of associated streptococcal infections to include necrotizing fasciitis.

Zosteriform Darier's disease versus acantholytic dyskeratotic epidermal nevus.

Patients with keratotic lesions distributed in a unilateral, linear, zosteriform or localized pattern and revealing histologic features of dyskeratotic acantholysis have been reported. There is still some controversy regarding the appropriate nosologic placement of this entity. Some believe it represents a localized form of Darier s disease, while others argue it is a variant of epidermal nevus. We report a case of a 42-year-old physician who presented with a 15-year history of an asymptomatic eruption that had been diagnosed as "chronic zoster." Physical exam revealed hyperkeratotic papules and plaques in a dermatomal distribution. The controversy regarding the correct nosologic placement of such a patient is discussed.

Altered expression of angiopoietins and Tie2 endothelium receptor in psoriasis.

Psoriasis is a chronic inflammatory skin disease in which epidermal proliferation is closely associated with excessive microvascular expansion within the papillary dermis. Angiopoietins have recently been identified as the major ligands of the endothelial- specific receptor Tie2. Angiopoietin 1 induces Tie2 signaling as a receptor activator and maintains blood vessel formation, whereas angiopoietin 2 destabilizes vessels by blocking Tie2 signaling as an antagonist of angiopoietin 1 and acts with vascular endothelial growth factor to initiate angiogenesis. In this study we examined the potential role of angiopoietins and the Tie2 receptor in vascular changes of psoriasis. Angiopoietin 1, angiopoietin 2, and Tie2 were upregulated in involved psoriasis skin compared to uninvolved psoriasis skin, healthy skin, and chronic spongiotic dermatitis skin. Angiopoietin 1 was expressed by stromal cells in the highly vascularized papillary dermis of involved psoriasis skin. Angiopoietin 2 was expressed by endothelial cells in the vicinity of the proliferating epidermis that abundantly expressed vascular endothelial growth factor. Vascular endothelial growth factor and basic fibroblast growth factor, which were overexpressed in involved psoriasis skin, enhanced angiopoietin 2 and Tie2 expression in dermal microvascular endothelial cell cultures. Thus, our findings suggest that upregulation of angiopoietin 1, angiopoietin 2, and Tie2 is closely associated with the development of microvascular proliferation in psoriasis, and that the angiopoietin-Tie2 system may act coordinately with vascular endothelial growth factor and basic fibroblast growth factor to promote neovascularization in psoriasis. Moreover, successful antipsoriatic treatment was accompanied by noticeable reduction of angiopoietin 2 expression, suggesting that alteration of angiopoietin 2 expression may be particularly important in controlling vascular proliferation in the treatment of psoriasis.

Collagen loss in photoaged human skin is overestimated by histochemistry.

It is well known that photoaged skin is characterized by increases in dermal matrix components that include glycosaminoglycans, proteoglycans and masses of abnormal elastic fibers accompanied by substantial collagen loss. Histochemical staining of such tissue gives the impression of "massive" loss of collagen and its replacement by these other matrix components. Early biochemical studies have lent support to this notion with a reported decrease in total collagen of approximately 45% compared to protected skin. More recent studies report considerably less, but varying, amounts of collagen loss. Rarely have the two approaches, histochemistry and biochemical analysis, been used in the same study to examine the same tissue. In this study, collagen loss was quantified biochemically in paired biopsies from sun-protected and sun-exposed arm skin of moderately photoaged female subjects (age 51-77 years). The values obtained were compared with histochemical and immunochemical findings. Quantitatively, collagen loss on a per mg protein basis was small compared to the histochemical appearance.

Basement membrane alterations in psoriasis are accompanied by epidermal overexpression of MMP-2 and its inhibitor TIMP-2.

Psoriasis is most probably an inherited disease characterized by cell proliferation, angiogenesis, and an inflammatory process. The pathophysiology remains unknown, although an alteration in cell-cell and cell-matrix adhesion versus an autoimmune process has been proposed as the primary defect. Here, we show evidence of a new mechanism involving basement membrane alterations accompanied by keratinocyte overexpression of matrix metalloproteinase (MMP) 2 and tissue inhibitor of MMP-2 (TIMP-2) in both uninvolved and involved psoriatic skin. Immunocytochemistry with antibodies against collagen IV (alpha1, alpha2 chains) and laminins (alpha2, alpha5, beta1, gamma1 chains) revealed gaps, folding, and reduplication of the epidermo-dermal basement membrane. There was overexpression of MMP-2 in the cytoplasm of suprabasal keratinocytes. Gelatin zymography revealed pro-MMP-2 and its activated form, a-MMP-2, in both uninvolved and involved psoriatic skin, whereas pro-MMP-9 was only present in involved skin. TIMP-2 was expressed at the cell surface of psoriatic involved suprabasal keratinocytes whereas it was restricted to basal keratinocytes in uninvolved areas. Western blots showed a marked increase in a-MMP-2 and TIMP-2 in uninvolved and involved psoriatic skin although it was more pronounced in the latter. MT1-MP, known to activate pro-MMP-2, was increased in involved areas. In situ hybridization revealed strong signals of MMP-2 mRNA in both uninvolved and involved psoriatic epidermis. The overexpression of MMP-2 in uninvolved and involved psoriatic epidermis supports the concept that the primary alteration may reside in the keratinocyte. In addition, the presence of the activated form of MMP-2 could be responsible for cell-cell and cell-matrix changes noted in psoriatic epidermis.

Pseudoxanthoma elasticum and calcinosis cutis.

A 42-year-old white woman presented with clinical and histologic manifestations of both calcinosis cutis and pseudoxanthoma elasticum: discrete milia-like calcifications at the anterior aspect of the neck, a funduscopic examination with classic eye findings, peripheral vascular disease, and a mottled appearance of the skin at the axillae, groin, and lateral aspects of the neck. A younger sibling had similar skin lesions and deteriorating visual acuity. The patient was normocalcemic and normophosphatemic. This case may represent the coincidental occurrence of two rare entities in the same person or may be suggestive of a pattern of dystrophic calcification associated with pseudoxanthoma elasticum.

All-trans-retinoic acid-induced scrotal ulcerations in a patient with acute promyelocytic leukemia.

Induction therapy with all-trans -retinoic acid has been shown to improve the outcome of patients with acute promyelocytic leukemia, although some side effects occur. Dry skin and lips are among the most common cutaneous side effects. We report a case of scrotal ulcerations induced by all-trans -retinoic acid in an American patient; to our knowledge this is the first such case reported.

Dermatofibrosarcoma protuberans in two patients with acquired immunodeficiency syndrome.

Dermatofibrosarcoma protuberans (DFSP) is a locally aggressive cutaneous tumor of intermediate malignancy. Most commonly, it arises as an asymptomatic, indurated plaque on the trunk within which protuberant nodules develop over time. We describe its occurrence in two patients with human immunodeficiency virus, a previously unreported association. The first patient, a 41-year-old woman, complained of painful lesions around the left shoulder that developed within a scar from previous trauma to the area. The second patient, a 50-year-old man, developed a recurrent DFSP within the scar from a previous surgical procedure. Dermatofibrosarcoma protuberans was confirmed in both cases by the histopathologic and immunohistochemical findings.

Pseudoxanthoma elasticum: an update.

Pseudoxanthoma elasticum (PXE) is an inherited disorder of elastic tissue with many systemic manifestations. The disease varies widely in its degree of expression and inheritance patterns and is believed to be considerably underdiagnosed due to lack of familiarity with the condition among physicians. The purpose of this article was to provide an update on important topics in PXE. Common presentations of the disease as well as the histopathology are discussed. The genetics of PXE as well as the importance of early diagnosis and genetic counseling are addressed. Special areas of concern, such as PXE in childhood, are reviewed. Finally, the article concludes with management of the disease and current areas of research.

Souvenir from the Hamptons - a case of cutaneous larva migrans of six months' duration.

Cutaneous larva migrans is a distinctive serpiginous eruption caused by a reaction to burrowing hookworms. The infection is usually self-limited, normally lasting 2-8 weeks, but may persist for more than a year if misdiagnosed. Biopsies of the creeping eruption rarely reveal an organism. Thus, it is important for the infection to be recognized clinically, so that effective treatment may begin. We found topical thiabendazole to be fast and effective in treating this case of cutaneous larva migrans of six months' duration.

Paraneoplastic pemphigus with a pemphigus vegetans-like plaque as the only cutaneous manifestation.

Paraneoplastic pemphigus (PNP) is a recently recognized autoimmune mucocutaneous disease associated with a few unusual lymphoreticular neoplasms. Intractable stomatitis is the most constant clinical feature but the cutaneous presentations are characteristically variable. We describe a patient with PNP associated with chronic lymphocytic leukemia who presented with severe oral, laryngeal, and pharyngeal involvement. The only cutaneous finding was a pemphigus vegetans-like plaque, a previously undescribed manifestation. The plaque evolved from a flaccid blister that formed at a prior intravenous catheter site. The mucosal biopsy specimen demonstrated faint intercellular staining with IgG, whereas results for the cutaneous plaque were negative. Indirect immunofluorescence testing was positive on both monkey esophagus and rat bladder epithelium. Immunoprecipitation (IP) studies demonstrated a complex of 4 proteins with molecular weights of 250, 230, 210, and 190 kd, confirming the diagnosis of PNP.