Adjuvant high-dose interferon alfa-2b in patients with high-risk melanoma.

We performed an analysis of toxicity and survival in stage III melanoma patients receiving adjuvant interferon alfa-2b (IFN). This was a retrospective single-arm analysis of 40 patients with stage III melanoma who received (IFN) administered at maximum tolerated doses of 20 mU/m2/day intravenously (i.v.) for 1 month and 10 mU/m2 three times per week subcutaneously (s.c.) for 48 weeks. Toxicity in our series is comparable to that experienced in the Eastern Cooperative Oncology Group (ECOG) 1684 trial, except for higher rates of dose-limiting myelosuppression and hepatotoxicity. All 40 patients experienced constitutional symptoms, but only 14/40 (35%) experienced grade 3 to 4 symptoms. Of the 40 patients, 36 (90%) experienced neurologic symptoms, but only seven (17.5%) experienced grade 3 to 4 neurotoxicity. Two patients stopped treatment because of severe psychiatric symptoms; one patient attempted suicide, and a psychosis developed in another. Thirty-nine (97.5%) patients experienced myelosuppression; 31 (77.5%) developing grade 3 to 4 myelosuppression. Hepatotoxicity was evident in 39 (97.5%) patients, and 26 (65%) experienced grade 3 to 4 hepatotoxicity. Three patients (7.5%) experienced mild renal toxicity. At a median follow-up of 27 months from initiation of therapy, there have been 19 relapses (47.5% disease-free survival [DFS]) and 10 deaths (75% OS) resulting from progression of disease. The DFS compares with the treatment arm in ECOG 1684 at 27 months, but overall survival is higher in our series of patients at the same time point. In a single program setting, IFN can be administered with similar side effects and outcome profiles seen in multi-institutional studies. Modifications in the induction regimen resulted in notably higher hematologic and hepatic toxicities but did not preclude administering further therapy and did not result in increased attrition rate among patients: only nine patients (22.5%) had their treatment stopped as a result of IFN-related toxicity. In comparison, 26% of patients had to have their treatment discontinued because of toxicity in ECOG 1684.

Off-label dermatologic therapies. Usage, risks, and mechanisms.

Off-label refers to the prescribing of Food and Drug Administration-approved drugs for a use not indicated on the package insert. The prescribing of off-label drugs may benefit patients with many dermatologic diseases including angiogenesis-related conditions. We surveyed 55 dermatologists from a single large academic program to assess their use of particular drugs for specific skin conditions, their perception of such use as being for Food and Drug Administration-approved or for off-label indications, and their attitudes towards off-label therapies. The practice of prescribing off-label drugs was common among the respondents, many of whom had misperceptions about which conditions are Food and Drug Administration-approved indications and about the legal ramifications of off-label therapies. We suggest that understanding the principles of off-label prescribing in conjunction with the mechanisms of drug action in diseases may help clinicians exercise their judgment in finding innovative therapies for their patients.

Lesions resembling malignant atrophic papulosis in a patient with dermatomyositis.

Many consider porcelain white atrophic papules as pathognomonic for malignant atrophic papulosis (MAP), or Degos' disease. During the past three decades, five patients with a collagen vascular disease have been reported to have MAP-like lesions as a manifestation of their underlying illness. We describe a patient with dermatomyositis who had porcelain-white atrophic papules resembling malignant atrophic papulosis.

Atypical angiomatosis in polyarteritis nodosa.

Biopsies from an area of livedo reticularis and adjacent to a leg ulcer in a woman with polyarteritis nodosa showed florid angioendothelial proliferation simulating angiosarcoma. This angioproliferative reaction has not been described previously in polyarteritis nodosa. Its microscopic differentiation from angiosarcoma is important.

Actinic reticuloid. Response to combination treatment with azathioprine, hydroxychloroquine, and prednisone.

We treated an intractable case of actinic reticuloid with azathioprine, hydroxychloroquine, prednisone, and solar protection with E-Z film and obtained a clinically worthwhile effect. The patient was initially sensitive to less than 2 mjoules/cm2 ultraviolet B (UVB) and less than 1 joule/cm UVA, which caused erythematous and infiltrated scaly plaques that persisted for more than 6 weeks after testing. The case is also instructive in the difficulty presented in differentiating it from mycosis fungoides, and for the presence of Sézary-type cells in skin, blood, and lymph nodes.

Necrotizing vasculitis from radiographic contrast media.

Two patients in whom cutaneous necrotizing vasculitis and nephritis developed 12 to 22 hours after the intravascular injection of radiocontrast media are presented. In one patient, the fortuitous observation was made of sparing of the skin from vasculitis in an area into which xylocaine and epinephrine had been injected 4 hours prior to administration of the radiocontrast material. The possible mechanisms by which these reactions may have taken place and the potential implications are discussed.

Necrotizing vasculitis within cutaneous lesions of mycosis fungoides.

Mycosis fungoides is a T cell lymphoma with a predilection for cutaneous involvement. This paper describes the clinical manifestations and histopathologic features of a case of mycosis fungoides with necrotizing vasculitis localized to the lesions of cutaneous lymphoma. Elevated levels of circulating immune complexes were found in this patient. The large numbers of perivascular malignant helper T lymphocytes may have induced immunoglobulin synthesis, resulting in the formation of these complexes followed by deposition in vessel walls and subsequent necrotizing vasculitis. Possible alternative mechanisms include the presence of anti-T cell antibodies, or cytotoxic effector cells.

Nonrashes. Part I: The Koebner nonreaction.

"Nonrashes" range from pruritus that may signal an underlying systemic illness to delusional parasitosis associated with severe psychological disturbance. We report another kind of nonrash, the Koebner nonreaction or isomorphic nonresponse, that was manifested by the absence of a drug rash at the site of recently administered x-irradiation. We also present a compilation of a number of other nonrashes, such as the mitempfindungen (referred itch) and the prodrome of herpes zoster. The recognition of certain types of nonrashes may be lifesaving.

Cutaneous lesions in disseminated candidiasis mimicking ecthyma gangrenosum.

Cutaneous nodules are recognized as a manifestation of disseminated candidiasis. We describe skin lesions clinically identical to ecthyma gangrenosum that, on microscopic examination, were due to Candida emboli rather than Pseudomonas sepsis. Thus, the appearance of necrotic pustules and ulcerative plaques in the immunocompromised patient would raise the possibility of Candida as well as Pseudomonas sepsis, and illustrates the diagnostic importance of skin biopsy in such cases.

Uveitis, poliosis, hypomelanosis, and alopecia in a patient with malignant melanoma.

Bilateral uveitis, poliosis, hypomelanosis, and alopecia (Vogt-Koyanagi-Harada syndrome) developed spontaneously in a 57-year-old woman following operation for metastatic malignant melanoma. She has been disease-free for 8 1/2 years in spite of a highly unfavourable prognosis. Within the framework of current concepts of cell-mediated and humoral immunity in patients with malignant melanoma, activity of the host's immune system is postulated for the destruction of normal melanocytes in the skin, hair follicle, and uveal tract, as well as for the favorable outcome.

Cryotherapy of basal-cell carcinoma by a simple method of standardized freeze-thaw cycles.

One hundred seventy-seven basal-cell carcinomas treated by cryotherapy with liquid nitrogen according to a standard protocol had a recurrence rate of 2.3% in a mean of 4.8 years of follow-up. The cryotherapeutic method used freeze-thaw times rather than temperatures measured by thermocouples as indices of adequacy of freeze.

Prolonged ultraviolet light-induced erythema and the cutaneous carcinoma phenotype.

A considerable amount of evidence exists in support of the role of ultraviolet radiation as a major etiologic factor in human skin cancer, both melanoma and carcinoma types. On the basis of epidemiologic studies a phenotype has been described which helps to identify the persons who are more susceptible to skin cancer. In an attempt to further define this population, patients with cutaneous carcinoma and a normal control group were exposed to artificial ultraviolet light (UVL) and the erythema and tanning responses of each group were measured over a 21-day period. UVL-induced erythema was prolonged in a significantly higher percentage of patients with skin cancer than in control patients, lasting two to three weeks after single exposures to 6 and 8 times the patient's minimal erythema dose. The presence of prolonged erythema correlated with this history of previous skin cancer but did not correlate with other established risk factors for cutaneous carcinoma, i.e., fair skin, light hair and light eyes, easy sunburning and poor tanning, and Celtic ancestry. Prolonged erythema following UVL radiation may therefore represent an additional risk factor and help to identify the skin cancer-susceptible population.

Oral methoxsalen photochemotherapy of mycosis fungoides.

The cutaneous manifestations of mycosis fungoides have been successfully treated in nine patients for 16 to 28 months with oral methoxsalen and subsequent irradiation with longwave ultraviolet light. The efficacy of this therapy was confirmed in one patient, who showed complete clearing of generalized plaques after 1 month (12 treatments) except for a shielded control area which worsened during this period. Methoxsalen photochemotherapy may prove a valuable addition to therapies currently available for mycosis fungoides and may obviate some of the problems associated with conventional management of this disorder.