Hemorrhagic diathesis associated with benign histiocytic, cytophagic panniculitis and systemic histiocytosis.

Five patients had a histiocytic, cytophagic panniculitis and a febrile, progressive course, which included hepatosplenomegaly, pancytopenia, liver function abnormalities, and a hemorrhagic death. The terminal hemorrhage was characterized by features of intravascular coagulation and liver failure. The histiocytosis could be found at times also in bone marrow, lymph nodes, liver and spleen, and serosal tissues, as well as in skin and subcutaneous tissue. Adequate biopsy diagnosis will prevent such cases from being labeled as Weber-Christian disease with bleeding, and offer an opportunity for appropriate treatment of this new syndrome of histiocytic, cytophagic panniculitis.

The Merkel cell system and a comparison between it and the neurosecretory or APUD cell system.

The Merkel cell, a neural crest migrant to the skin, possesses a characteristic intranuclear rodlet, cytoplasmic membrane-bound granules, and horn projections and is usually associated with nerve terminations. It is also associated with all types of known organizations of sensory nerve endings in the skin and possesses characteristic enzyme reactions in relation to the ending. The Merkel cell is found in the skin and the oral mucous membranes, and similar cells are observed in the taste buds and pulmonary tissue. A comparison between the Merkel cell and the APUD cell system of polypeptide hormone and amine-producing cells reveals many structural and chemical similarities.

Autotransplantation in pustular psoriasis.

Five women with chronic pustular psoriasis of the soles were subjected to transplantation of full thickness cylinders of tissue between normal glabrous skin and involved plantar skin. Concomitant psoriasis was present in only one of the patients. All patients developed typical pustular psoriasis in normal skin implanted in the foot, while previously involved plantar skin reverted to normal scar when placed in glabrous areas.

New observations in the histopathology of erythema nodosum.

Erythema nodosum presents variable clinical and histologic patterns of response in the vessels, septa, and fat lobules of the subcutaneous tissue. Acute or chronic phlebitis with hemorrhage may be commonly observed; acute panniculitis is observed in foci, but at time it may be the principal histologic feature; lymphocytic infiltration of fat lobules is often found, and lymphoid nodules are not infrequent; rarely, chronic granulomatous lesions involve septa or fat lobules; and proliferative lipocyte response may be observed. Because these variable histologic patterns may be coexistent, excision biopsy and multiple sections are necessary to recognize them. The variable histologic features correlate with the different clinical forms: acute nodular, chronic nodular, migrating plaque lesion, cellulitis, and the rate suppurative form. This variety of panniculus response in erythema nodosum can be explained on the basis of host-tissue response to a delayed hypersensitivity reaction to an antigenic stimulus.

Cutaneous neuropathology in multiple endocrine neoplasia, type 2b.

Increase in masses of mixed (myelinated and nonmyelinated) nerve are observed in the dermis of clinically normal skin of patients with multiple endocrine neoplasia, type 2b (MEN 2b). Preliminary histochemical studies revealed nucleoside triphosphatase and nonspecific acid esterase. Electron microscopy showed axonal organelles, mild degeneration of axons, and numerous axons unassociated with Schwann cells. The normal-appearing skin in MEN 2b seems to contain abnormal nerve tissue development equally with the mucosal and the gastrointestinal tract.

The human cutaneous basement membrane--anchoring fibril complex: preparation and ultrastructure.

The human cutaneous basement membrane (CBM) has been isolated together with the anchoring fibrils (AF) of the dermis. These structures are removed from the dermis as a single complex, the CBM-AF complex. The epidermis is first removed from the dermis by immersion of whole, defatted skin in cold 2 n NaSCN for 5 to 6 hr. Subsequently, removal of the CBM-AF complex is effected by focusing high-intensity ultrasonic energy against the dermal surface. Purification of the preparation is achieved by low-speed sedimentation. All stages of the process were monitored by electron microscopy, which demonstrated that the morphology of the CBM-AF complex was well preserved and that this complex represents the principal mass component in the system. In addition, our report describes an ultrasound-induced variation in collagen fibril morphology, which we have called 'disordered collagen.' This altered type of fibril lacks periodicity or recognizable banding and has a frayed appearance. Finally, the experiments provide the basis for an analysis of the relative strengths of certain bonds at the dermal--epidermal junction. The strongest of these appears to be the bond between basement membrane and anchoring fibril.

IgE in human eccrine sweat.

By the use of a sensitive and specific double antibody radioimmunoassay, immunoglobulin E was demonstrated in sweat from 6 of 11 healthy volunteers; the concentrations of IgE ranged from 1 to 3.9 ng/ml of sweat. Six of seven patients with dermatitis and elevated levels of serum IgE also had high IgE levels in sweat; the highest IgE value in sweat was 75.5 ng/ml and was noted in a patient with atopic dermatitis. Thus, all the main immunoglobulin classes can be demonstrated in eccrine sweat.

Lipid synthesis in cutaneous xanthoma.

In vitro lipogenesis was studied on the xanthoma tissue from 6 patients with normal plasma lipids and 4 patients with hyperlipidemia. Xanthoma tissue was incubated at 37 degrees C for 6 hr in Krebs-Ringer phosphate buffer containing sodium [14C]acetate. The radioactivity of each lipid class was determined after extraction and separation of lipids. The incorporation of acetate into all major lipid groups was much greater in xanthoma tissue than in control normal-appearing skin. There was no difference in the incorporation pattern of 14C between xanthomas of patients with normal plasma lipids and those of hyperlipidemic patients. The data exemplify considerable in situ lipid synthesis of xanthoma tissue. Although the lipids in xanthomas of hyperlipidemic persons may be derived from plasma, the plasma origin of xanthoma lipids in normolipidemic persons remains to be confirmed, and the contribution of local lipogenesis cannot be ignored. The lipids in cutaneous xanthomas are most likely derived from a multiple input system.

Prostaglandins and chemotaxis: enhancement of polymorphonuclear leukocyte chemotaxis by prostaglandin F2alpha.

Prostaglandins E1, E2, F1alpha, and F2alpha did not demonstrate direct in vitro chemotactic properties either to rabbit peritoneal polymorphonuclear leukocytes or to rabbit or human polymorphonuclear leukocytes isolated from blood. Prostaglandin F2alpha, however, enhanced the chemotactic responsiveness of human polymorphonuclear leukocytes to the chemotactic agent casein.

Inflammation in acne vulgaris: leukocyte attraction and cytotoxicity by comedonal material.

The chemoattraction of comedonal material for leukocytes was evaluated. Material from open comedones attracted mononculear leukocytes but did not attract polymorphonuclear leukocytes. At higher concentrations, comedonal material was cytotoxic for leukocytes of both types. Of the comedonal components tested, free fatty acids produced the greatest cytotoxicity. The attraction and killing of leukocytes by comedonal components may be the mechanisms for the initiation or the enhancement (or both) of inflammation in acne vulgaris.

Dermal mast cell activation by autoantibodies against the high affinity IgE receptor in chronic urticaria.

Previous studies identified autoantibodies against the IgE high affinity receptor alpha-chain, Fc epsilon RI alpha, in sera of selected patients with severe chronic idiopathic urticaria. We have now determined the incidence of anti-Fc epsilon RI alpha autoantibodies in a group of 163 patients. Intradermal injection of autologous serum caused skin reactions indicative of mast cell degranulation in 98 (60%) patients. Based on histamine release from IgE-sensitized and nonsensitized basophil leukocytes of healthy donors, we detected anti-Fc epsilon RI alpha autoantibodies in sera from 38 (23%) urticaria patients and evidence for anti-IgE antibodies in a further nine patients. The sera that released histamine from basophils induced histamine release (4-34%, n = 12) from mast cells in incubated skin slices. Protein-G affinity chromatography of sera demonstrated that mast cell histamine release was IgG-mediated. Preincubation of sera or the IgG fraction with a recombinant alpha-chain of Fc epsilon RI inhibited histamine release from mast cells and basophils. Further studies with the mouse anti-human Fc epsilon RI alpha antibody 29C6 showed that mast cells and basophils were similarly sensitive to IgG-mediated direct cross-linking of Fc epsilon RI, with 0.01-1.0 micrograms/ml 29C6 evoking histamine release in each case. These studies demonstrate that circulating levels of anti-Fc epsilon RI alpha autoantibodies mediate histamine release from skin mast cells in vitro and, taken together with in vivo evidence of mast cell degranulation following intradermal injection of autologous serum, support the concept that anti-Fc epsilon RI alpha autoantibodies are relevant to the pathogenesis of severe chronic urticaria in about 25% of patients.

Necrobiotic xanthogranuloma with paraproteinemia. A review of 22 cases.

Cutaneous biopsy specimens from 22 patients showed the distinctive histopathologic pattern of necrobiotic xanthogranuloma within the dermis or subcutaneous tissue (or both). Twenty of the 22 patients had 1 or more serum protein abnormalities, consisting of an IgG monoclonal protein in 16, multiple myeloma in 3, cryoglobulinemia in 3, and an abnormal serum protein electrophoresis in 1. Cutaneous lesions were seen as discrete, slowly developing red nodules and plaques with a xanthomatized hue and a predilection for the face (periorbital region in particular), trunk, and extremities. Ulceration was a notable finding in 10 patients. Histologically, the dermis and lobules of subcutaneous tissue were involved with a granulomatous infiltrate containing bands of hyaline necrobiosis and bizarre foreign body, as well as Touton giant cells. Cholesterol clefts, lymphoid nodules with or without germinal centers, and foci of plasma cells were variable but significant features. Leukocyte monoclonal antibody studies in 6 patients demonstrated helper T cells within the granulomas. Electron microscopy in 3 cases showed lipid vacuoles in macrophages in the dermis and dendritic cells in the epidermis, and study confirmed this entity as a non-X histiocytosis. Pertinent laboratory findings, in addition to the serum protein abnormalities, included elevation of the erythrocyte sedimentation rate, leukopenia with absolute neutropenia, and decreased serum complement levels, as well as decreased levels of C1-esterase inhibitor in some patients. Thirteen of the 22 patients have survived, the mean duration being 9.5 years after the onset of cutaneous disease. While given to only a few patients in the current series, low-dose chemotherapy seems to induce a favorable response in both the cutaneous and the hematologic disease.

Acral arteriovenous tumor. A clinicopathologic review.

We reviewed 47 cases of a distinctive, benign vascular tumor, acral arteriovenous tumor. Study of the clinical histories of patients with this tumor emphasized the difficulty of making a clinical diagnosis. Most of the tumors were asymptomatic and were found in generally healthy middle-aged or elderly male patients. Distribution was acral; 79% of the tumors were located on the head or extremities. Histologic study showed a component of capillary nevus in some cases in addition to the typical venous and arteriovenous channels.

Treatment of lichen planus.

Lichen planus is an inflammatory pruritic dermatosis in which T lymphocytes attack the basal epidermis, producing characteristic clinical and histological lesions. Mild cases can be treated successfully with rest, topical corticosteroids with or without wet dressings, or occlusion. Severe generalised cases may require systemic corticosteroids. Chronic, aggressive lesions may need additional therapy ranging from psoralen plus ultraviolet A (PUVA) to retinoids or cyclosporin. Complications ranging from infectious, bullous disease or ulceration require special treatment considerations.

The current treatment of scleroderma.

The treatment of scleroderma is determined by the stage of the disease, associated organ involvement, or the presence of features overlapping those of other connective tissue disease. Raynaud's phenomenon is responsive to vasoactive medication, but recently heat and plasma exchange have been shown to be more effective, reducing the need for systemic medication. In stages II and III of the disease, administration of non-toxic penicillamine in low doses for 2 to 4 years is the preferred treatment. Plasma exchange may offer some hope in the early stages. The treatment of the renal crisis of scleroderma with angiotensin-converting enzyme inhibitors has reduced mortality from this complication. These drugs are currently the preferred treatment for the hypertension of renal scleroderma. The symptomatic treatment of the pulmonary, gastrointestinal, and soft tissue complications of scleroderma is also discussed.

Porphyria cutanea tarda and chronic renal failure.

Bullous dermatosis developed in a patient with renal failure who was on hemodialysis. The results of standard tests for porphyria cutanea tarda--quantitation of urinary and fecal porphyrins by fluorometric assay--were within normal limits or were nondiagnostic. Assay of plasma using high-pressure liquid chromatography, however, revealed that this patient had a porphyrin profile consistent with porphyria cutanea tarda. A porphyria-like bullous eruption may occur in patients with chronic renal failure; however, in only a few cases have laboratory studies confirmed the diagnosis of porphyria cutanea tarda. Our experience suggests that, in patients with renal failure, a plasma assay may be more reliable than tests of the urine and feces in establishing a diagnosis in those patients who actually have disorders of porphyrin metabolism. We also report the results of assay of erythrocyte uroporphyrinogen decarboxylase activity and fecal isocoproporphyrin.

Successful treatment response of granuloma annulare and carpal tunnel syndrome to chlorambucil.

We describe a 62-year-old woman in whom skin biopsies verified the clinical diagnosis of granuloma annulare and neurologic and electromyographic studies confirmed the neurologic diagnosis of carpal tunnel syndrome. Short-term treatment with a low dose of chlorambucil taken orally was prescribed. Within weeks, the granuloma annulare had disappeared, and the clinical symptoms of carpal tunnel syndrome had resolved. Electromyography showed variable improvement at the end of treatment and resolution at 9-month follow-up. Our case confirms that short-term treatment of granuloma annulare and associated carpal tunnel syndrome with low-dose chlorambucil is successful.

Cutaneous gangrene, vascular calcification, and hyperparathyroidism.

We describe the development of necrotic ulcers with underlying vascular calcification in a 72-year-old man who had chronic renal failure. These lesions had surrounding ecchymoses. The patient had a normal serum calcium concentration, an elevated parathyroid hormone level, and findings consistent with a parathyroid adenoma on ultrasonography. We consider this another case of a characteristic cutaneous syndrome secondary to underlying vascular calcification and hyperparathyroidism.

Morphologic heterogeneity of malignant lymphomas developing in mycosis fungoides.

From an extensive series of patients with mycosis fungoides, we identified 12 in whom subsequently developing extracutaneous (lymph nodal) lymphoma manifested morphologic features other than those of so-called cutaneous T-cell lymphoma. Six patients had features diagnostic of Hodgkin's disease, two had morphologic and cytochemical features consistent with T-cell lymphoma but without the morphologic features ascribed to cutaneous T-cell type, and four had morphologic characteristics most consistent with B-cell lymphoma. Although in most cases of mycosis fungoides the lymphomas exhibit morphologically distinctive features of mycosis cells, we propose that in occasional cases this morphologic correlation is not present.

The evolution of Hodgkin's disease and necrobiotic xanthogranuloma syndrome.

We describe a woman in whom hypogammaglobulinemia and severe granulomatous cutaneous lesions had developed during childhood; subsequently, Hodgkin's disease and necrobiotic xanthogranuloma were diagnosed. This case illustrates an apparent association with disease activity and raises the question of a direct relationship of necrobiotic xanthogranuloma with lymphoproliferative disease.