Merkel cell polyomavirus and human papilloma virus in proliferative skin lesions arising in patients treated with BRAF inhibitors.

The potential role of oncogenic viruses mediating development of proliferative skin lesions in patients treated with RAF inhibitors is poorly understood. The objective of this study was to investigate human papilloma virus (HPV) and Merkel cell polyomavirus (MCPyV) in skin lesions among patients treated with RAF inhibitors with the help of a case series describing prevalence of HPV, MCPyV, and RAS mutations in skin biopsies obtained from patients receiving RAF inhibitors and developing cutaneous lesions. HPV-DNA was amplified by PCR utilizing multiple nested primer systems designed for detection of a broad range of HPV types. MCPyV copy number determination with real time PCR technology was performed by a "Quantification of MCPyV, small t region" kit. Thirty-six patients were tested (squamous cell carcinoma (SCC) = 14; verruca vulgaris = 15; other = 11). Nine of 12 SCCs (75 %) and eight of 13 verruca vulgaris lesions (62 %) tested positive for MCPyV whereas none of the normal skin biopsies obtained from nine of these patients tested positive for MCPyV (p = 0.0007). HPV incidence in cutaneous SCCs was not different compared to normal skin (50 vs. 56 %, p = 0.86). The association between MCPyV and proliferative skin lesions after RAF inhibitor therapy merits further investigation.

A randomized trial of minoxidil in chemotherapy-induced alopecia.

BACKGROUND: Hair loss is a side effect of many chemotherapeutic agents, and patients have even refused possibly palliative or lifesaving drugs because they could not accept temporary or prolonged baldness. Topical minoxidil has been shown to be effective for androgenetic alopecia and alopecia areata. OBJECTIVE: Our purpose was to investigate the value and safety of minoxidil in chemotherapy-induced hair loss. METHODS: Twenty-two women who were facing adjuvant chemotherapy after breast surgery were registered in a protocol that used a 2% minoxidil topical solution or a placebo in a randomized double-blind trial. RESULTS: There was a statistically significant difference (favoring minoxidil) in the interval from maximal hair loss to first regrowth. Thus the period of baldness was shortened (mean, 50.2 days) in the minoxidil group. CONCLUSION: Minoxidil decreased the duration of alopecia caused by chemotherapy. There were no significant side effects.

Pustular psoriasis induced by hydroxychloroquine: a case report and review of the literature.

A variety of pharmacologic agents have been known to induce pustular psoriasis. We describe a patient with a positive personal and family history of psoriasis who developed an extensive annular pustular eruption 3 weeks after starting hydroxychloroquine (Plaquenil) for arthritis. The drug was discontinued, and she received 3 weeks of systemic and topical corticosteroids; in spite of the therapeutic intervention, showers of new lesions appeared daily, and progressed to involve 75% of the body. The development of new lesions stopped, and the older lesions began to clear after one dose of 7.5 mg of methotrexate. Subsequently, methotrexate therapy was stopped because of mild transaminase elevation; the pustular lesions then flared. New lesions stopped appearing after four doses of weekly methotrexate. The patient remains clear of lesions 6 months later.

Lingual hyperpigmentation associated with minocycline therapy.

Minocycline can cause hyperpigmentation of the conjunctiva, oral mucosa, and skin. Pigmentation of the oral mucosa may also be associated with a variety of endogenous or exogenous factors. Lingual pigmentation may be seen in Addison's disease, amalgam tatoo, malignant melanoma, Peutz-Jegher's syndrome, and other diseases. Two women who had isolated pigmentation of the tongue while taking minocycline are described; no other drug-induced pigmentation of their oral mucosa or skin occurred. Minocycline-induced pigmentation should be added to the differential diagnosis of isolated lingual hyperpigmentation.

Linear and dermatomal cutaneous graft-versus-host disease.

A 17-year-old girl had linear and dermatomal lichenoid chronic graft-versus-host disease (GVHD) 18 months after receiving an allogeneic bone marrow transplantation for aplastic anemia. The cutaneous GVHD lesions appeared on previously normal skin.

A phase-I clinical study of low-dose oral interferon-alpha.

Twenty-five patients with systemic malignancies or cutaneous disorders were treated with low dosages (1-16 IU/kg/day) of oral interferon-alpha in a phase-I study. There were no grade-3 or -4 toxicities. No patients achieved a partial or complete response. One patient with renal cell carcinoma had prolonged disease stabilization lasting for 22 months. No significant changes in lymphocyte subsets including T4/T8 ratio, or serum immunoglobulins were observed. Subjective improvement in general well-being was reported by three patients. Low dosages of interferon-alpha administered orally do not appear to have any significant immunomodulatory or antitumor activity.

Secondary syphilis presenting as cutaneous nodules in a patient previously treated for laryngeal carcinoma.

A person who had previously been treated for laryngeal carcinoma presented with the new onset of asymptomatic nodular skin lesions. The preliminary differential diagnosis included cutaneous metastasis. Examination of a biopsy specimen of the lesions and results of subsequent laboratory investigation ruled out the possibility of recurrent metastatic disease and established a diagnosis of secondary syphilis. The differential diagnosis of nodular lesions that resemble a lymphoid neoplasm or a cutaneous metastasis in a patient treated for cancer should also include secondary syphilis.

Concomitant unilateral idiopathic atrophoderma of Pasini and Pierini (IAPP) and morphea. Observations supporting IAPP as a variant of morphea.

A 17-year-old black man suddenly developed an unilateral eruption of clinically apparent lesions of idiopathic atrophoderma of Pasini and Pierini (IAPP) and concomitant lesions of morphea. Histologically the lesions are indistinguishable. IAPP appears to be a variant of morphea.

The expanding role of lymphoscintigraphy in the management of cutaneous melanoma. First Place Winner: Conrad Jobst award.

Accepted therapy for intermediate-thickness melanomas is wide local excision and regional lymphadenectomy for nodes known to be in the lymph drainage basin. Lymphoscintigraphy has been shown to be of great help in predicting the drainage pattern of truncal, shoulder, proximal extremity, and head and neck melanomas. Lymphoscintigraphy using Technetium-99 antimony sulfur colloid was performed on 17 patients with cutaneous melanomas at H. Lee Moffitt Cancer Center at the University of South Florida. Of 13 patients with primary truncal and shoulder lesions, drainage patterns were discordant 54 per cent of the time and resulted in dissection of nodal groups different than would otherwise have been planned. This resulted in several lymph nodes positive for metastatic disease removed from operative sites not expected to show metastatic spread by clinical experience alone. The discordant rate for head and neck drainage was also high with 2 of 3 forehead studies showing drainage to both anterior and posterior cervical chains when only anterior chain drainage was expected, while only one of these drained to the preauricular nodes. Again, this led to elective lymph-node dissections of nodal basins not anticipated on clinical grounds alone. After a mean follow-up of 2 years, in which 60 to 75 per cent of all recurrences from melanoma are expected to occur, there has been no lymph-node metastasis development in basins that were not predicted by the scan. It is clear from our data that well-known historical patterns of lymph drainage in addition to the clinical impression of experienced surgeons cannot reliably predict the lymphatic drainage of many truncal, shoulder, and head and neck melanomas.(ABSTRACT TRUNCATED AT 250 WORDS)

Chronic cutaneous lupus erythematosus.

Chronic cutaneous LE is a diverse disease, characterized by predominantly cutaneous disease with few systemic complications. Discoid lesions are commonly seen, but they are not specific for chronic cutaneous LE. These scarring and disfiguring changes are also present in neonatal LE, SLE, and complement deficiency LE. Because definitive diagnosis cannot be made by cutaneous examination alone, all patients should initially be evaluated for systemic disease. A small percentage of patients with chronic cutaneous LE will ultimately develop SLE, and therefore, patients should be re-evaluated periodically. The pathogenesis of the cutaneous lesions is not definitively known. There is suggestive evidence implicating T-cell mediated injury, especially in discoid LE. Antibody-dependent cellular cytotoxicity may also play a significant role in cellular damage in subacute cutaneous LE and neonatal LE, especially in the presence of anti-Ro antibody. Immunoglobulin deposition in association with membrane attack complex, has been associated with epidermal injury in some cases. Treatment of chronic cutaneous LE is largely symptomatic and nonspecific, focusing on reduction of inflammation. Further knowledge of pathogenesis will, hopefully, provide for specific immunologic therapy.

Lupus erythematosus.

Lupus erythematosus represents a wide spectrum of diseases. Within this heterogeneity, however, several clinically relevant subsets have been found that may unite differing aspects of the disease and that may have pathogenic implications for the problem as a whole. Exciting links between genetic phenotypes, certain immune responses, and related cutaneous findings in neonatal, complement-deficient, subacute cutaneous, and ANA-negative lupus erythematosus and Sjögren's syndrome have been found. The increased frequency of the anti-Ro(SSA) antibody in these groups is notable. The ultraviolet light-altered immune system found in vivo and in vitro may also be relevant to disease pathogenesis. Even if the mechanisms elaborated are not the precise aberrations in lupus erythematosus, they may serve as an operational model for further research. Continued investigations into mechanisms of photoexacerbations in lupus erythematosus, as well as into genetically mediated immune response, may further our understanding of these disorders.

Bullous sclerodermalike changes in chronic graft-vs-host disease.

Cutaneous sclerodermalike changes are a well-documented manifestation of chronic cutaneous graft-vs-host reaction. We describe a patient with chronic cutaneous graft-vs-host reaction who developed vesicles and bullae on sclerodermoid skin 18 months after bone marrow transplantation. The vesicles and bullae were subepidermal in location by light microscopy and were associated with dilated lymphatics and a sparse perivascular mononuclear cell infiltrate. No deposition of immunoreactants was seen by immunofluorescent microscopy. Electron microscopy confirmed the presence of a subepidermal blister beneath an intact basement membrane zone and surrounded by marked dermal edema. We postulate that localized lymphedema may play a role in the development of these vesicles and bullae.

Cutaneous busulfan effect in patients receiving bone-marrow transplantation.

Epidermal keratinocytes with abnormally large nuclei were found in 12 of 13 patients who received high-dose busulfan and cyclophosphamide prior to receiving bone-marrow transplantation for treatment of hematological malignancies. These cells were similar to those previously described in the lungs, cervix and bladder of patients on long-term busulfan therapy. Marked keratinocyte nuclear abnormalities were not observed in bone-marrow transplant recipients who received a preparatory regimen of cyclophosphamide and total-body irradiation. This histologic cutaneous busulfan effect was transient and was unrelated to the development of graft-versus-host reaction.

Cutaneous graft-versus-host reaction: prognostic features seen by light microscopy.

Acute graft-versus-host disease (GVHD) is a severe complication of bone marrow transplantation. The diagnosis may be made and its course followed by serial skin biopsies. The degree of epidermal change has been used as a guideline in grading each biopsy, but great variation may be found within each grade, especially grade 2 (basal cell vacuolization and dyskeratosis). To find a histologic parameter that is prognostic of more severe acute GVHD, we examined retrospectively the serial biopsies of 54 patients. When we studied early cutaneous graft-versus-host reaction (GVHR), represented by the grade 2 biopsies, the number of dermal and epidermal mononuclear inflammatory cells correlated positively with the probability of developing more severe acute GVHD. In addition, the patients who had more severe acute GVHD tended to have an earlier appearance of cutaneous histologic changes. None of the other histologic parameters examined in these grade 2 biopsies were found to be predictive of GVHD progression. In addition, no histopathologic parameters in these grade 2 biopsies were predictive of the subsequent development of chronic GVHD.