Impact of adding an IgG4 conjugate to routine direct immunofluorescence testing for subepithelial and intraepithelial autoimmune blistering disorders.

BACKGROUND: Certain autoimmune bullous dermatoses are mediated by autoantibodies of the IgG4 subclass. We determined the diagnostic impact of adding IgG4 to our conventional direct immunofluorescence (DIF) panel. METHODS: For all cases submitted to our referral laboratory for DIF over 1 month (n = 630), we performed IgG4 testing and collected consecutive biopsy specimens showing definite or indeterminate linear or cell-surface deposition of IgG, IgG4, and/or C3. On retrospective blinded review, we classified the pattern and whether the findings were definite, indeterminate, or negative. When present, substantial background staining was recorded. RESULTS: Seventy DIF specimens met the inclusion criteria. Of 22 (31.4%) specimens equivocal for linear or cell-surface deposition, 9 (40.9%) had definitive IgG4 findings, either linear (3 of 14 equivocal linear cases; 21.4%) or cell-surface (6 of 8 equivocal cell-surface cases; 75.0%). Background deposition was substantial in 14 cases (20.0%) for IgG but in none for C3 or IgG4. CONCLUSION: IgG4 allowed the classification of over 40% of DIF cases that were otherwise equivocal by IgG and C3. IgG4 staining showed lower levels of non-specific background staining than IgG or C3. IgG4 appears to contribute most value in cases with cell-surface deposition or with equivocal linear IgG deposition and negative C3 results.

Radiation-induced pemphigus or pemphigoid disease in 3 patients with distinct underlying malignancies.

The cutaneous lesions of radiation-induced pemphigus or pemphigoid disease may resemble other skin diseases, including recurrent underlying cancer. We performed a computerized search of Mayo Clinic (Rochester, Minnesota) archives and identified 3 cases of pemphigus or pemphigoid disease that occurred after radiation therapy for breast, cervical, and metastatic malignancies, respectively. In 2 of these patients, the disease was initially confined to the irradiated field but subsequently disseminated to other parts of the patients' bodies, including mucosal surfaces. In all 3 patients, the blistering disease occurred 5 to 14 months after the onset of radiation therapy. All 3 were treated with corticosteroids and demonstrated complete recovery of the skin eruption after radiotherapy was discontinued. Although the precise mechanism of this cutaneous eruption is unknown, clinicians should be alert for this potentially serious complication and evaluate all cutaneous eruptions developing during and after radiotherapy.

Pneumocystis jiroveci pneumonia in patients treated with systemic immunosuppressive agents for dermatologic conditions: a systematic review with recommendations for prophylaxis.

Pneumocystis jiroveci pneumonia is an opportunistic infection associated with substantial rates of mortality in immunosuppressed patients. Prophylaxis recommendations are mostly targeted toward patients with non-dermatologic diagnoses. This study was conducted to determine when dermatology patients treated with immunosuppressive medications should be offered P. jiroveci pneumonia prophylaxis. We searched the literature from January 1, 1993, to December 31, 2013, using terms relating to P. jiroveci pneumonia and dermatologic diagnoses to analyze the clinical characteristics of previously affected patients. Guidelines for P. jiroveci pneumonia prophylaxis from other medical fields were also analyzed. Of 17 dermatology patients reported to have contracted P. jiroveci pneumonia, eight (47.1%) died of the pneumonia. Risk factors included lack of prophylaxis, systemic corticosteroid therapy, lymphopenia, hypoalbuminemia, low serum CD4 counts, comorbid pulmonary or renal disease, malignancy, and prior organ transplantation. The present conclusions are limited by heterogeneity among the selected studies and limitations in their identification and selection. However, P. jiroveci pneumonia in dermatology patients is associated with a high mortality rate. Based on our analysis, we propose that prophylaxis be considered in dermatology patients in whom treatment with systemic corticosteroids at doses exceeding 20 mg/day or treatment with corticosteroid-sparing immunosuppressive agents is anticipated for at least 4 weeks, and in patients with additional risk factors for P. jiroveci pneumonia.

Frequency of cutis laxa-like clinical features and elastolysis in scleromyxedema: a retrospective clinicopathologic study of 19 patients with scleromyxedema.

BACKGROUND: Cutis laxa-like features were observed in a subset of patients with scleromyxedema. Given this observation, clinical and histopathologic features of scleromyxedema were reviewed in correlation with elastic tissue staining. METHODS: We retrospectively reviewed clinical records and histopathologic features from patients with scleromyxedema seen at our institution from 1992 through 2013. We also evaluated available skin biopsies with an elastin stain and assessed whether dermal elastin fibers were diminished in density or were fragmented (or both). RESULTS: Nineteen patients with scleromyxedema and 34 skin biopsies were identified. Alcian blue (mucin) stain was used to grade mucin deposition as weakly positive (24%), positive (44%) and markedly positive (32%). Eight patients (42%) had clinical findings of cutis laxa, which were often observed in conjunction with areas of papular eruption or induration. Elastic tissue fibers were normal in 9 of 34 skin specimens (26%), 18 of 34 specimens (53%) had diminished elastic fiber density and 7 of 34 (21%) had markedly decreased density. The elastic tissue was fragmented in 25 specimens (74%). CONCLUSIONS: A cutis laxa-like clinical presentation and decreased elastic tissue density on skin biopsy were consistent findings. Dermatologists and dermatopathologists should be aware of these previously unreported clinical and histopathologic findings.

CAM use in dermatology. Is there a potential role for honey, green tea, and vitamin C?

Complementary and alternative medicine (CAM) is a group of non-traditional medical practices that includes natural products, manipulations, and mind and body medicine. CAM use has grown and become popular among patients. In dermatology, honey, green tea, and vitamin C have been used as topical treatments for a variety of diseases. We performed a systematic review to explore the cutaneous effects of each of these three products. Honey's unique antibacterial, anti-inflammatory, and antioxidant properties were shown to contribute to wound healing, especially in ulcers and burns. Green tea, among many health benefits, demonstrated protection from ultraviolet-induced events, such as photoimmunosuppression and skin cancer growth. Vitamin C, known for its antioxidant properties and key role in collagen production, has been shown to produce positive effects on skin hyperpigmentation and aging. Future large well-designed clinical trials are needed in order to further investigate the potential of these agents as dermatological therapies.

Combination cytokine therapy inhibits tumor growth by generation of tumor-specific T-cell responses in a murine melanoma model.

Various cytokines, including interferon alpha (IFNalpha), tumor necrosis factor alpha (TNFalpha), and granulocyte-macrophage colony-stimulating factor (GM-CSF), have been used as adjuvant therapy for advanced-stage melanoma with some success but with marked toxicity, which appears to be related to higher doses. We investigated the efficacy of IFNalpha, GM-CSF, and TNFalpha in various combinations to induce antitumor and immune responses in a B16F10 murine melanoma model. These studies showed that GM-CSF, IFNalpha, and TNFalpha, when injected together intratumorally, mediated significant inhibition of tumor growth. Tumor regression correlated with local tumor necrosis and significant infiltration of T cells. In addition, this injected intralesional cytokine cocktail also induced lymphadenopathy, with an increase in both CD4(+) and CD8(+) T cells in the draining lymph nodes. Furthermore, tumor-specific CD8(+) T cells were identified from draining lymph nodes. These investigations identify the combined effects of IFNalpha, GM-CSF, and TNFalpha in induction of the adaptive immune response and generation of antigen-specific T-cell reactivity. These results support potential clinical trials of the low-dose cytokine combination as adjuvant therapy for melanoma.

Cytokine therapy in advanced melanoma.

Patients with melanoma considered at high risk for recurrence or regional metastases often have to choose between adjuvant interferon therapy or enrolling in a clinical trial. High-dose interleukin-2 therapy has had limited success in producing durable responses in stage IV melanoma; this success has been offset by marked toxicity. High-dose interferon alpha therapy has consistently shown disease-free survival benefit in clinical trials but has marked toxicity. The overall survival benefit has been inconsistent and controversial. Treatment with granulocyte macrophage colony-stimulating factor has shown promise in early studies. Various cytokines have had some success in treating advanced stage melanoma but with marked toxicity. Cytokine therapy that is well-tolerated and consistently provides an overall survival benefit for high-risk melanoma patients has not been achieved. Cytokines will continue to have a role in therapy for advanced-stage melanoma, most likely in combination with other immunomodulatory therapy. The challenge is finding the right doses, frequency, combinations, and duration of treatment.

Cutaneous complications of intravesical treatments for bladder cancer: granulomatous inflammation of the penis following BCG therapy and penile gangrene following mitomycin therapy.

Transitional cell carcinoma of the bladder is frequently treated with intravesical injection of immunotherapeutic (eg, BCG) or chemotherapeutic (eg, mitomycin C) agents. The aim of this study was to report cutaneous complications of intravesical therapy in 2 patients with transitional cell carcinoma of the bladder. A 69-year-old man had an ulceration at the base of the penis and papules involving the glans penis 1 month after injection of intravesical BCG. Biopsy findings showed granulomatous inflammation with foci of dermal necrosis suggestive of a BCG-related granulomatous reaction. The second patient was a 73-year-old man with penile gangrene. Erythema involving his penis and perineum had developed within 24 hours after intravesical administration of mitomycin C, which spilled onto his perineum during catheter removal. The resulting penile gangrene required penectomy 3 months after the injection. Mitomycin C patch testing showed a clear allergic contact reaction. Dermatologists should be aware of these potential cutaneous complications.

Cytokines in dermatology.

Cytokines are polypeptides that are produced by various cell types and act in an autocrine or paracrine manner. They have many different biological actions and have been used in dermatology to treat a wide range of dermatologic diseases. In this paper we review some of the more commonly used cytokines in dermatology, including interferon-alpha and -gamma, interleukins-2 and -10, and granulocyte-macrophage colony-stimulating factor. We specifically examine their roles in the treatment of condyloma and verruca, hemangiomas, keloids, skin cancers, atopic dermatitis, psoriasis, Behcet disease, chronic granulomatous disease, wound healing, and cutaneous T cell lymphoma. In addition, some of the adverse effects associated with these cytokines are discussed.

Plasmapheresis for refractory urticarial vasculitis in a patient with B-cell chronic lymphocytic leukemia.

BACKGROUND: Urticarial vasculitis is a form of cutaneous leukocytoclastic vasculitis clinically characterized by persistent and often painful urticarial lesions. Numerous systemic diseases have been associated with urticarial vasculitis, including certain hematologic disorders. This distinctive form of cutaneous necrotizing vasculitis can be resistant to standard therapeutic modalities, necessitating more aggressive intervention. METHODS: We report a case of refractory urticarial vasculitis developing in association with B-cell chronic lymphocytic leukemia in a 46-year-old man. We also reviewed the literature to identify other cases of urticarial vasculitis managed with this therapeutic modality. RESULTS: The disease progressively improved during 6 treatments with plasmapheresis (plasma exchange). In the additional cases identified in the literature, plasmapheresis was generally effective and well tolerated. CONCLUSION: On the basis of these findings, we propose that plasmapheresis be considered a treatment option for refractory urticarial vasculitis.

Management of multifocal primary cutaneous CD30 anaplastic large cell lymphoma.

Primary cutaneous CD30(+) anaplastic large cell lymphoma in adults is rare, but the prognosis is generally excellent. Skin lesions may be localized or, less commonly, multifocal. Although not extensively reported, multifocal primary cutaneous anaplastic large cell lymphoma tends to relapse after systemic chemotherapy and is generally considered more prone to progress to extracutaneous involvement than the localized disease. We report the case of a 21-year-old woman with primary cutaneous CD30(+) anaplastic large cell lymphoma manifesting as widespread papules and nodules. Despite remaining localized to the skin, the disease relapsed after multiple chemotherapy regimens and autologous stem-cell transplantation. Treatment with an experimental anti-CD30 monoclonal antibody was successful. Review of this case and similar cases illustrates that traditional combination chemotherapy may not be best. Newer treatments, including anti-CD30 monoclonal antibodies, show promise. However, further study is needed to develop optimal therapeutic strategies.

Recurrent palmoplantar hidradenitis with exclusive palmar involvement and an association with trauma and exposure to aluminum dust.

Recurrent palmoplantar hidradenitis is a benign, self-limited inflammatory skin condition that has been reported to occur on the soles and palms of otherwise healthy children and young adults. Patients with the disease present with tender, erythematous and edematous plaques and nodules on the palmoplantar skin. We describe a child who had recurrent palmoplantar hidradenitis that occurred after trauma and exposure to aluminum dust and manifested as lesions localized to only the palmar surfaces. This case is presented to add exclusive palmar involvement to the diagnostic spectrum of recurrent palmoplantar hidradenitis and to review the proposed pathogenesis of the disease.