Abstract Purpose Here, we report the feasibility and long-term efficacy of a granulomatous slack skin disease (GSSD) treatment with combined high-energy photon and proton beams. Patient and methods A GSSD patient with abdominal disease volume 25×15×2–4 cm deep was recommended for treatment at this institution. In addition to photons and electrons, high-energy protons delivered with advanced planning techniques and patient positioning were used. The patient was irradiated to a total dose of 40 Gy by using 20 Gy matched photon and electrons followed by 20 Gy equivalent protons delivered by using innovative range compensation and patient positioning. Results The test patient tolerated the treatment well and is now a 10-year survivor of the disease. Conclusions Treatment of GSSD with protons is feasible. The range and narrow penumbra properties of the proton beam provided an ideal capability to match fields accurately to cover large volumes while also sparing underlying normal tissues.

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.

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.

BACKGROUNDDiffuse 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.OBSERVATIONSA 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.CONCLUSIONSClinical acumen is crucial to diagnose diffuse angiomatosis of the breast. Appropriate treatment to alleviate hypoxia may improve the patient's condition.

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.

RATIONALE: Airborne fungi have been implicated as a possible cause of chronic rhinosinusitis (CRS), with mediation by sensitized lymphocytes. In this study, we have tested by patch testing, whether patients with CRS have lymphocytes sensitized to Alternaria and other airborne fungi. METHODS: Patch testing was performed with allergen extracts of Alternaria tenuis, Aspergillus fumigatus, Candida albicans, Curvularia spicifera, Helminthosporium, Hormodendrum, Penicillium, Trichoderma viride and Trichophyton rubrum on 23 patients with seasonal allergic rhinitis (SAR), 10 patients with CRS with history of previous sinus surgery for CRS, 13 patients with CRS with no history of sinus surgery and 24 healthy controls. Concentrations used for the patch testing were based on concentrations used for skin prick testing and concentrations used for immunotherapy. Two concentrations were used for each fungus. The patch tests were graded by dermatologists at 48 and 96 hours on a 0-4 scale. RESULTS: Of the 23 patients with SAR, 1 patient was positive to Alternaria, Candida, Penicillium and Trichophyton. Of 13 patients with CRS and no previous surgery, 1 was positive to Aspergillus. All 10 patients with CRS and previous sinus surgery for CRS were negative to testing. Of 24 healthy controls, 4 had positive responses to one or more of the allergens tested. CONCLUSION: In this study setting, we found no evidence of delayed hypersensitivity to fungal allergens in patients with CRS. The unexpected finding of positive patch testing to fungal allergens in healthy controls and SAR is puzzling and deserves further investigation.

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 pemphigoid [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. To examine retrospectively the use and effectiveness of intravenous immunoglobulin (IVIg) treatment of various skin diseases, primarily immunobullous disease. 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. Eighteen patients were treated with IVIg for various skin diseases: immunobullous disease in 11 adults (pemphigus vulgaris [7 patients], bullous pemphigoid [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. 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.

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.

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.

We appreciate the interest of Dr. Miller and colleagues. Our review article has 151 references. Obviously, we could review only the main points in each reference and not critique each one of them. We agree with Dr. Miller and associates that radiotherapy is most beneficial for painful or cosmetically troublesome Kaposi's sarcoma and that complications with use of radiation therapy for oral Kaposi's sarcoma are severe. Extreme caution should be exercised when irradiation is used for visceral organs in patients with the human immunodeficiency virus (HIV). The brief report by Drs. Narasimhan and Hitti was interesting. As we demonstrated in our review article, multiple atypical or exaggerated symptoms can occur in patients with HIV infection. Because emergency tracheostomy provides immediate relief for these patients, we appreciate the authors sharing their experience.

In patients with alcoholic liver disease, IgA deposits are often found in the liver, kidneys and skin. The present study was undertaken to determine the specificity, sensitivity and characteristics of IgA deposition in the skin of a group of alcoholic patients with or without overt liver disease, and compare these with findings in non-alcoholic cirrhotics. Twenty-six out of 28 patients with alcoholic cirrhosis had IgA deposition in the skin. In contrast, only 6 out of 11 patients who were alcoholic without any clinical liver disease and 3 out of 13 patients with non-alcoholic cirrhosis of the liver had IgA deposition. In the control group, only 1 out of 52 patients with various dermatoses (excluding IgA dermatoses) had this IgA deposition. Unlike other IgA dermatoses, such as Henoch-Schoenlein purpura or dermatitis herpetiformis, IgA deposition in alcoholic liver disease is characterized by its presence in the basement membrane of the eccrine secretory coils. This particular pattern of IgA deposition can be helpful in the diagnosis of alcoholic liver disease or alcoholism since the specificity is 100% with a sensitivity of 75%.

Treatment with cyclosporine is beneficial for many dermatologic diseases such as psoriasis, lichen planus, Behçet disease, atopic dermatitis, pyoderma gangrenosum, and epidermolysis bullosa acquisita. The selective action of cyclosporine on helper T cells and its rapid therapeutic action and weak myelotoxicity are the key advantages in the treatment of many dermatologic diseases. Nevertheless, drug toxicity, especially nephrotoxicity, high rates of relapse after treatment cessation, and high cost have limited its use to those diseases refractory to other therapies. Herein we discuss the use of cyclosporine for dermatologic diseases relative to efficacy, dosage, safety profile, and monitoring. In addition, we review the formulations and metabolism of cyclosporine; discuss its mechanism of action, clinical indications in dermatology, and side effects; and provide usage guidelines for this drug. Cyclosporine can be safely administered when potential toxicities, dosing, and monitoring guidelines are known.

Dermatology has given rise to syphilology, which ties the specialities of dermatology and venereology closely together. Venereology was long dominated by the classical venereal diseases gonorrhea and syphilis. Lately the term sexually transmissible diseases (STDs) has been introduced to illustrate the rapid expansion of the area. It is indeed significant that we today only mention gonorrhea and syphilis in passing — although substantial progress has indeed been made in these fields too — in order to focus on the new challenges.

It is not known whether patients with anti-epiligrin cicatricial pemphigoid (AECP) have an increased risk of malignancy. We calculated the expected numbers of cancers in a c hort of 35 such patients based on respective incidence rates for all cancers in the National Cancer Institute's Surveillance, Epidemiology, and End Results (NCI SEER) Registry. Ten patients in this cohort had solitary solid cancers; eight patients developed cancer after onset of AECP (seven within 14 months). The relative risk (RR) for cancer in this cohort was 6·8 (95% confidence intervals [CI]: 3·3-12·5). AECP seems to be associated with an increased relative risk for cancer.

Fifty patients with chronic idiopathic urticaria were studied to compare responses to treatment with doxepin (10 mg three times a day) and with diphenhydramine (25 mg three times a day). All patients had an evaluation that failed to disclose a cause for their disease. Therapeutic response was assessed according to the suppression of symptoms and symptom diary scores of daily itching and frequency, number, size, and duration of hives. Total clearing of the pruritus and urticarial lesions occurred in 43% of the patients while receiving doxepin and in only 5% while receiving diphenhydramine (p less than 0.001). Partial or total control of the pruritus and hives was noted in 74% of the patients receiving doxepin and in only 10% of those receiving diphenhydramine (p less than 0.001). Doxepin induced markedly less sedation (22%) than diphenhydramine (46%) (p less than 0.05). Dermatopathologic categories included (1) urticaria simplex, (2) lymphocytic urticaria, and (3) leukocytoclastic urticaria. Patients with urticaria simplex had a more favorable response to doxepin than the two other groups.

We have developed an immunoradiometric assay for IgE antibodies to Staphylococcus aureus (Staph IgE-Ab) which uses purified cell walls (PCW) from the Wood 46 strain of S. aureus as an immunosorbent. We compared Wood 46 PCW and whole organisms (WO) as immunosorbents for Staph IgE-Ab by performing tests on sera from patients with atopic dermatitis (AD) or the hyperimmunoglobulin E syndrome (hyper IgE syndrome). Sera with Staph IgE-Ab demonstrated dose-dependent binding to PCW and WO, but the ratio of specific to non-specific binding was much greater with PCW. Mean non-specific binding to WO was greater than to PCW, 5% versus 2%; and non-specific binding to WO varied directly with the serum concentration of IgE. Results of tests on patients' sera indicated that PCW are required in screening assays for Staph IgE-Ab to avoid false positive results caused by high levels of non-specific binding to WO.

The study of ten cases of cutaneous periarteritis nodosa by direct immunofluorescence microscopy of excision biopsy specimens revealed positive findings in nine. Deposition of IgM was found in the vessel walls in six cases, and C3 was observed in four; however, only in two cases was C3 found with IgM in the vessel walls. Deposits of IgM in the superficial vessels were found in five cases, although only the deep muscular vessels showed evidence of the vasculitis in cutaneous periarteritis nodosa. Serum hepatitis B antigen was absent in the nine cases that were tested. Positive immunofluorescence findings in superficial as well as in deep vessels suggest that although periarteritis nodosa is characterized by an inflammatory panarteritis, occasional vasculitis of small vessels might be expected.

The classification of lupus erythematosus (LE) is difficult because of variable and multisystem involvement, occurrence of transitional forms, and overlapping with connective tissue disorders. One of the earliest attempts at classification was made by O'Leary (1934), who classified LE clinically into four main types: (1) chronic discoid lupus erythematosus (DLE), or fixed type with the typical erythematous, scaly, well‐demarcated eruption, usually showing follicular plugging and atrophy, confined to the head region; (2) generalized DLE, or chronic disseminated type differing from the localized discoid type in that the erythematous plaques are found not only on the head area but also below the neck region (O'Leary considered that constitutional systems were generally lacking in these two types); (3) subacute disseminated LE; and (4) acute disseminated LE. The last two categories reflect what we now call systemic lupus erythematosus (SLE) of varying severity. Many authors have used O'Leary's clinical classification, but progress in laboratory medicine—in particular the discovery of the LE cell—has led to other schemes, the most widely accepted at present being that related to the American Rheumatism Association's (ARA) preliminary criteria for the diagnosis of SLE (Cohen et al., 1971). These criteria have been criticized by many authorities because they do not include important data, such as those relative to the antinuclear antibody test, serum anti‐native‐DNA, serum complement levels, many neurological abnormalities, renal biopsy changes, and cutaneous immunofluorescent (IF) findings. However, Dubois (1974b) pointed out that all categorizations of LE are arbitrary, and he accepted the ARA criteria as a successful method for differentiating LE. This report involves the clinical and laboratory findings in 123 patients with LE seen at the Mayo Clinic during the 3‐year period 1971–1974 and an assessment of the validity and usefulness of O'Leary's classification.