Vitamin D-mediated hypercalcemia in slack skin disease: evidence for involvement of extrarenal 25-hydroxyvitamin D 1alpha-hydroxylase.

UNLABELLED: A case of granulomatous slack skin disease is presented in which we studied the possible involvement of extrarenal 1,25(OH)2D in the pathogenesis of the patient's hypercalcemia. Immunolocalization of 1alpha-OH in skin showed simultaneous dysregulation in epithelial and granulomatous cells. INTRODUCTION: Granuloma-forming diseases such as sarcoidosis are associated with extrarenal synthesis of active 1,25-dihydroxyvitamin D [1,25(OH)2D]. Here we describe a case of granulomatous slack skin disease in which we have studied the possible involvement of extrarenal synthesis of 1,25(OH)2D in the pathogenesis of the patient's hypercalcemia. The aim of the study was to clarify the etiology of hypercalcemia in this patient. MATERIALS AND METHODS: This was a case study of a 19-year-old man with a T-cell lymphoproliferative disorder diagnosed as granulomatous slack skin disease who presented with hypercalcemia and raised serum 1,25(OH)2D. Analysis of expression of the enzyme 25-hydroxyvitamin D 1alpha-hydroxylase (1alpha-hydroxylase), which catalyzes synthesis of 1,25(OH)2D, was carried out by immunohistochemical analysis of involved and uninvolved skin. Approval was granted by the Mayo Foundation Institutional Review Board and Biospecimens Subcommittee. RESULTS: In uninvolved skin, expression of 1alpha-hydroxylase was confined to the basal layer of the epidermis, whereas slack skin showed overexpression of the enzyme in dermal granulomata and basal cells of the epidermis. CONCLUSIONS: Hypercalcemia associated with granulomatous slack skin syndrome seems to be caused by dysregulation of 1alpha-hydroxylase expression in both epidermal and dermal granulomatous cells. This contrasts with psoriasis and sarcoidosis of the skin, in which overexpression of the enzyme is restricted to keratinocytes and granulomata, respectively.

Diffuse dermal angiomatosis of the breast.

BACKGROUND: Diffuse dermal angiomatosis is rare and usually considered a variant of reactive angioendotheliomatosis. It generally involves the extremities of patients with severe vascular disease and other comorbidities. Two patients with breast involvement have been described; however, neither had a relevant medical history or a vaso-occlusive disorder, but both had large pendulous breasts, and 1 was positive for IgM anticardiolipin and antinuclear antibodies. OBSERVATIONS: A 53-year-old woman had a reticulated, erythematous plaque with superficial ulceration and underlying tender nodules on her left breast. She had a history of cardiovascular disease and was a heavy smoker. Biopsy of the lesion showed diffuse proliferation of additional endothelial cells and small bland vessels within the papillary and upper reticular dermis. Angiography showed almost complete occlusion of the subclavian artery proximally. Diffuse dermal angiomatosis was diagnosed. With isotretinoin therapy, the lesions improved. One month later, after percutaneous subclavian arterial revascularization, the lesion resolved completely. A literature review suggested that a history of heavy smoking, in addition to a history of vascular disease, may be important in the pathogenesis of diffuse dermal angiomatosis. CONCLUSIONS: Clinical acumen is crucial to diagnose diffuse angiomatosis of the breast. Appropriate treatment to alleviate hypoxia may improve the patient's condition.

Effectiveness of intravenous immunoglobulin therapy for skin disease other than toxic epidermal necrolysis: a retrospective review of Mayo Clinic experience.

OBJECTIVE: To examine retrospectively the use and effectiveness of intravenous immunoglobulin (IVIg) treatment of various skin diseases, primarily immunobullous disease. PATIENTS AND METHODS: We identified patients who had received IVIg therapy for skin disease between 1996 and 2003 at the Mayo Clinic in Rochester, Minn, Scottsdale, Ariz, and Jacksonville, Fla, and retrospectively reviewed their medical records. RESULTS: Eighteen patients were treated with IVIg for various skin diseases: immunobullous disease in 11 adults (pemphigus vulgaris [7 patients], bullous pemphigold [3], and cicatricial pemphigoid [1]); dermatomyositis (2); mixed connective tissue disease (1); chronic urticaria (1); scleromyxedema (1); leukocytoclastic vasculitis (1); and linear IgA bullous disease (1). Responses of patients by type of disease were as follows: pemphigus vulgaris, 1 partial response (PR) and 6 no response (NR); bullous pemphigoid, 1 complete response (CR) and 2 NR; cicatricial pemphigoid, 1 NR; dermatomyositis, 1 CR and 1 PR; mixed connective tissue disease, 1 CR; chronic urticaria, 1 CR; scleromyxedema, 1 CR; leukocytoclastic vasculitis, 1 PR; and linear IgA bullous disease, 1 CR. Six patients (33%) experienced CR, 3 (17%) had PR, and 9 (50%) had NR to IVIg therapy. All 9 nonresponders were adult patients with immunobullous disease. CONCLUSION: Although this was a retrospective study of a small cohort of a mixture of patients, the findings emphasize that our experience with IVIg treatment for skin disease, particularly immunobullous disease, is less favorable than that reported previously. Further studies are needed to verify the efficacy of IVIg for skin disease.

Successful treatment of scleromyxedema with autologous peripheral blood stem cell transplantation.

BACKGROUND: Scleromyxedema is a rare chronic fibromucinous disorder that can have devastating clinical manifestations, including sclerosis of the skin with progressive pharyngeal and upper airway involvement, resulting in high mortality due to respiratory complications. Herein we describe a novel therapeutic approach. Because autologous hematopoietic stem cell transplantation is effective in other plasma cell proliferative disorders, it may be effective in this setting. OBSERVATIONS: We retrospectively evaluated 6 patients who were offered high-dose chemotherapy with stem cell rescue as treatment for scleromyxedema. One heavily pretreated patient was unable to mobilize stem cells. The remaining 5 patients mobilized stem cells and underwent successful transplantation. There was no treatment-related mortality. Hematologic responses were seen in 4 patients, including 2 complete remissions and 2 partial remissions, and all 4 had improvement in extracutaneous manifestations. All 4 patients subsequently had relapse of the monoclonal protein, and 3 developed skin relapses at 14, 37, and 45 months. CONCLUSIONS: High-dose chemotherapy with stem cell rescue is feasible for patients with scleromyxedema and, although not curative, offers durable remission in most patients. This therapy should be considered before treatment with alkylating agents or other treatments that could adversely affect the ability to collect stem cells.

Patch test results from the Mayo Clinic Contact Dermatitis Group, 1998-2000.

BACKGROUND: Patch testing is a diagnostic tool for the evaluation of patients with suspected allergic contact dermatitis. A standard series of allergens similar to that used by the North American Contact Dermatitis Group (NACDG) is used at Mayo Clinic. OBJECTIVE: Our aim was to report the results of patch testing with a standard series at Mayo Clinic from July 1, 1998, to Dec 31, 2000 and to compare our findings with those of the NACDG during the same period. METHODS: The results of patch testing with the standard series at Mayo Clinic were examined. Positive reaction rates were compared between Mayo Clinic and the NACDG. RESULTS: During the 30-month period, 1324 Mayo Clinic patients were patch tested with a standard series of allergens (mean, 60 allergens), whereas the NACDG standard series during this period included 50 allergens. Overall, 917 patients (69.3%) had at least one positive reaction and 606 patients (45.8%) had two or more positive reactions. The 10 allergens used both by Mayo Clinic and by the NACDG that most frequently caused positive reactions were nickel sulfate hexahydrate, balsam of Peru (Myroxylon pereirae), neomycin sulfate, cobalt chloride, fragrance mix, potassium dichromate (0.25%), thimerosal, bacitracin, formaldehyde, and glutaraldehyde. Statistically significant differences in positive reaction rates (P < .05) were observed for 12 of the 43 allergens common to both Mayo Clinic and the NACDG. CONCLUSION: With large standard patch test series, one can identify commonly encountered and potentially relevant contact allergens.

Changing trends and allergens in the patch test standard series: a mayo clinic 5-year retrospective review, january 1, 2001, through december 31, 2005.

OBJECTIVE: To present and interpret results of patch testing with the Mayo Clinic standard series over 5 years. DESIGN: Retrospective study. A standardized patch testing technique was used. Data were recorded on a standardized computer program from January 1, 2001, to December 31, 2005, and analyzed. SETTING: Tertiary referral center. PATIENTS: Patients who were referred for patch testing. INTERVENTION: Patch testing with the "standard series," ie, a standard series of allergens used by most clinicians to identify the most common offending allergens in patients with allergic contact dermatitis. MAIN OUTCOME MEASURES: Number of patients patch tested, allergens used over this period, and rates of allergic patch test reactions to allergens. RESULTS: A total of 3854 patients (mean age, 55.1 years; age range, 6.2-99.4 years; 2576 female [66.8%]) were tested. All dermatologists in the department performed patch testing. The mean number of allergens included was 69.3 (range, 6-87). There were 2664 patients with at least 1 positive reaction (69.1%) and 1933 with 2 or more positive reactions (50.2%). Metals, fragrances, topical antibiotics, preservatives, and individual allergens used in hair-care products, topical corticosteroids, glues, plastics, and rubber were still the most common allergen groups associated with allergic patch test reactions. CONCLUSIONS: We describe the structure of the patch testing service at our referral center. Ongoing analysis of our patch test reaction rates allows us to recommend broad, clinically relevant, and up-to-date allergens for testing.

Necrolytic migratory erythema: clinicopathologic study of 13 cases.

BACKGROUND: The clinical mucocutaneous manifestations of glucagonoma syndrome are recognized easily when they occur in the classic pattern of acral or periorificial lesions evolving in recurrent crops, with an annular and migratory distribution, in a patient with diabetes mellitus who has had recent weight loss and anemia. Not infrequently, noncharacteristic clinical and histopathologic features are observed and, in these cases, the diagnosis of pancreatic neoplasm may be delayed. AIM: To review the clinical and histopathologic features of cutaneous manifestations of glucagonoma syndrome. METHODS: The clinicopathologic features of 13 patients (eight women) with widespread or localized cutaneous eruption as a manifestation of islet cell pancreatic carcinoma with marked glucagon secretion (glucagonoma) were reviewed. RESULTS: The definitive diagnosis of the cutaneous eruption was established at the time of diagnosis of the pancreatic neoplasm (three patients) or afterwards (10 patients). In nine patients, the mucocutaneous manifestations preceded the diagnosis of the pancreatic neoplasm by 1 month to 3 years (mean, 12 months). In only eight biopsy specimens were the histopathologic features considered to be suggestive or characteristic of necrolytic migratory erythema. Diffuse parakeratosis, that occasionally arose abruptly from normal epidermis, was observed in 12 biopsy specimens. By the time necrolytic migratory erythema was diagnosed, the pancreatic carcinoma had metastasized to the liver, regional lymph nodes, or bone in 12 patients. CONCLUSION: Increased awareness of the polymorphic mucocutaneous and nonspecific histopathologic features of glucagonoma syndrome is needed to avoid unnecessary delay in the diagnosis of this syndrome.