Pentoxifylline attenuates UVB-induced cutaneous erythema.

BACKGROUND: The mechanism for ultraviolet-B (UVB)-associated cutaneous erythema may involve production of tumor necrosis factor alpha (TNF-alpha). Pentoxifylline inhibits TNF-alpha production. OBJECTIVE: To assess the effect of oral pentoxifylline on UVB-induced erythema in humans. METHODS: Baseline minimum erythema doses (MEDs) for UVB were measured. Subjects received pentoxifylline 400 mg orally every 8 h for 4 doses. MED assays were repeated 2 h after the last dose of pentoxifylline. Pre- and posttreatment MED results were assessed by the paired t test. RESULTS: Oral administration of pentoxifylline to 7 normal adults elevated the MED for UVB in all 7 individuals. CONCLUSION: Pentoxifylline may diminish the cutaneous sunburn response to UVB radiation when it is administered prior to ultraviolet exposure.

Pediatric cutaneous malignant fibrous histiocytoma.

Malignant fibrous histiocytoma (MFH) is an aggressive soft-tissue sarcoma that most commonly occurs in the skeletal muscle of the extremities or retroperitoneum of adults. Although the majority of MFH is located beneath the fascia, the tumor occasionally occurs in the subcutaneous tissue. MFH rarely occurs in children and the disease course, prognosis, and outcome in younger patients has not been well described. We report a case of cutaneous MFH presenting on the thigh of a 12-year-old boy.

Learning and memory difficulties after environmental exposure to waterways containing toxin-producing Pfiesteria or Pfiesteria-like dinoflagellates.

BACKGROUND: At the beginning of autumn, 1996, fish with "punched-out" skin lesions and erratic behaviour associated with exposure to toxins produced by Pfiesteria piscicida or Pfiesteria-like dinoflagellate species were seen in the Pocomoke River and adjacent waterways on the eastern shore of the Chesapeake Bay in Maryland, USA. In August, 1997, fish kills associated with Pfiesteria occurred in these same areas. People who had had contact with affected waterways reported symptoms, including memory difficulties, which raises questions about the human-health impact of environmental exposure to Pfiesteria toxins. METHODS: We assessed 24 people who had been exposed. We collected data on exposure history and symptoms, did a complete medical and laboratory assessment (13 people), and carried out a neuropsychological screening battery. Performance on neuropsychological measures was compared with a matched control group. RESULTS: People with high exposure were significantly more likely than occupationally matched controls to complain of neuropsychological symptoms (including new or increased forgetfulness); headache; and skin lesions or a burning sensation of skin on contact with water. No consistent physical or laboratory abnormalities were found. However, exposed people had significantly reduced scores on the Rey Auditory Verbal Learning and Stroop Color-Word tests (indicative of difficulties with learning and higher cognitive function), and the Grooved Pegboard task. There was a dose-response effect with the lowest scores among people with the highest exposure. By 3-6 months after cessation of exposure, all those assessed had test scores that had returned to within normal ranges. INTERPRETATION: People with environmental exposure to waterways in which Pfiesteria toxins are present are at risk of developing a reversible clinical syndrome characterised by difficulties with learning and higher cognitive functions. Risk of illness is directly related to degree of exposure, with the most prominent symptoms and signs occurring among people with chronic daily exposure to affected waterways.

Pfiesteria and the skin: a practical update for the clinician.

Skin complaints, including an episodic burning sensation on contact with river water, were common among 13 persons with exposure to Maryland's Pocomoke River in the summer of 1997. While the majority of findings on dermatologic examination were unrelated to toxic dinoflagellate exposure, a subset of patients demonstrated otherwise unexplained erythematous, edematous papules on the trunk or extremities. Histopathologic findings were suggestive of an inflammatory, toxic, or allergic process. It may be speculated that these otherwise unexplained cutaneous findings represent a cutaneous reaction to Pfiesteria or Pfiesteria-like toxin; however, further evaluation of future affected persons will be warranted.

Teledermatology and in-person examinations: a comparison of patient and physician perceptions and diagnostic agreement.

OBJECTIVE: To compare physician and patient impressions and interphysician diagnostic agreement between live teledermatology and in-person examinations. DESIGN: Paired video and in-person examinations with different dermatologists. SETTING: An urban Veterans Affairs dermatology clinic. PATIENTS: One hundred thirty-nine patients. MAIN OUTCOME MEASURES: Satisfaction questionnaires and interphysician diagnostic agreement. RESULTS: Patient and physician satisfaction was high. Agreement between video and in-person diagnoses was 80%. CONCLUSIONS: Physicians and patients were satisfied with teledermatology examinations. Diagnostic agreement between in-person and video dermatologists was high.

Diagnosis and treatment of cutaneous vascular lesions.

Cutaneous vascular lesions are the most common pediatric birthmarks. Flat vascular malformations tend to persist, but raised vascular lesions, known as hemangiomas, generally involute. Although not always necessary, treatment of flat lesions, if desired, is best accomplished with flash-lamp pumped pulsed dye laser. Therapy of hemangiomas varies depending on the presence of associated symptoms or syndromes. Specifically, hemangiomas that are likely to lead to loss of function or life ( e.g. lesions of internal organs, lesions associated with coagulopathy) should be treated promptly. Treatment may also be required for hemangiomas that are likely to lead to scarring when the lesion involutes, such as hemangiomas of the nose and lip. The natural history of hemangiomas includes proliferative, stationary and involutional phases. Many superficial hemangiomas resolve with minimal sequelae.

Herpes simplex vegetans: atypical genital herpes infection in a patient with common variable immunodeficiency.

Large papillomatous lesions clinically resembling verrucous carcinoma may be caused by viruses other than human papillomavirus. We report a case of recurrent vegetations covering the entire vulva in a pregnant patient with common variable immunodeficiency. Herpes simplex virus was recovered from these lesions. The patient did not respond to intravenous acyclovir, but her lesions dramatically healed with two courses of intravenous foscarnet. Repeated biopsies may prove necessary in cases such as this to ensure proper diagnoses.

Early presentation of pityriasis rubra pilaris.

Pityriasis rubra pilaris (PRP), a disorder of epidermal proliferation and altered keratinization, typically first appears as a scaly, erythematous patch on the upper portion of the body. Its initial appearance is nonspecific and may be confused with other common dermatoses. Subtle clinical findings and histologic changes in the early stage of PRP are helpful in the early diagnosis of this condition. We describe two cases to illustrate the initial manifestations of PRP and review the literature, emphasizing its early presentation and treatment.

Cutaneous histopathology of Rocky Mountain spotted fever.

The dermatologic diagnosis of Rocky Mountain spotted fever (RMSF) is often presumptive; the clinical presentation includes skin rash and febrile illness with or without a clear history of tick bite. The characteristic cutaneous manifestations include a generalized skin eruption with purpuric, blanching or non-blanching macules and papules usually involving the extremities. Although skin biopsies are often performed to confirm the diagnosis, the spectrum of cutaneous histopathology in RMSF has not been well described. We studied a series of 26 cases of RMSF, of which 10 were surgical specimens and 16 were autopsies. The microscopic changes were correlated with the duration of illness. The main histopathologic feature was lymphohistiocytic capillaritis and venulitis with extravasation of erythrocytes, edema, predominantly perivascular and some interstitial infiltrate. Leukocytoclastic vasculitis (LCV) with neutrophilic infiltrate and nuclear dust was seen in 11 of 15 (73%) specimens from involved skin. These lesions with LCV also showed notable epidermal change including basal layer vacuolar degeneration with mild dermoepidermal interface lymphocytic exocytosis. Six lesions with LCV displayed focal fibrin thrombi and capillary wall necrosis. Apoptotic keratinocytes were noted in 3 lesions with LCV. Subepidermal blister was observed in the skin lesion of an autopsied patient with LCV changes. Another lesion of a fatal case with LCV also contained features of acute neutrophilic eccrine hidradenitis. Focal small nerve twig inflammation was noted in a third autopsy case with LCV. Plasma cells were seen in 6 of 34 specimens (18%); and eosinophils were observed in 3 (9%). The subcutaneous fat contained a mild perivascular inflammation and one case revealed focal lobular neutrophilic inflammation. Immunohistologic (IH) staining using polyclonal rabbit anti-Rickettsia rickettsii demonstrated positive staining of the organisms in the affected endothelial cells in all 12 cases tested. The cutaneous histopathology of RMSF is caused by endothelial damage by the rickettsial organisms which elicit an initial lymphohistiocytic small vessel vasculitis with progression to LCV. The vasculitis in RMSF is, therefore, considered to be a form of septic vasculitis.

Tinea caput medusa: an unusual presentation of Trichophyton mentagrophytes on the scalp.

Tinea capitis has a wide variety of clinical presentations in adolescents and adults. However, the occurrence of fingerlike projections in the scalp has not been previously described. A 14-year-old girl presented with a one-year history of a painful scalp mass. Debridement of this mass revealed slender papillomatous growths resembling those seen in elephantiasis nostras verrucosa. A fungal culture grew Trichophyton mentagrophytes. We describe the first case of this unusual clinical variant of tinea capitis and hypothesize on its pathophysiological basis.

Cutaneous malacoplakia: a report of two cases and review of the literature.

Malacoplakia, an inflammatory disease characterized by accumulations of phagocytic macrophages, occurs primarily in immunocompromised individuals. Cutaneous involvement is rare. Two men, each with a renal allograft, had expanding nodules on the temple and perianal area (case 1) and perianal, inguinal, and scrotal skin (case 2). Lesions resolved after combined surgical and antibiotic therapy. Histopathologic examination showed dense infiltration with large phagocytic macrophages containing round, concentric, laminar Von Kossa stain-positive inclusion bodies. Histiocytes had positive results for CD 68, lysozyme, and alpha 1-antitrypsin. Electron microscopic examination demonstrated rare intracytoplasmic inclusion bodies with concentric electron-dense laminations of calcium (Michaelis-Gutmann bodies.) Cutaneous malacoplakia should be considered in the differential diagnosis of nodules or draining ulcers, particularly in immunocompromised patients. Because Michaelis-Gutmann bodies are difficult to identify, specimens should be evaluated for cutaneous malacoplakia by immunohistochemical or electron microscopic means.

Cutaneous eruptions from suramin. A clinical and histopathologic study of 60 patients.

BACKGROUND AND DESIGN: During a trial of suramin for advanced solid tumors, a high rate of cutaneous adverse reactions was observed. We present a prospective study, describing the clinical, histopathologic, histochemical, and immunochemical findings of the cutaneous reactions observed in 60 patients treated with suramin. RESULTS: Forty-nine (82%) of the 60 patients studied experienced at least one cutaneous reaction attributable to suramin therapy. Although morbilliform reactions predominated, a wide variety of eruptions was observed. Most reactions occurred within the first 24 hours of therapy and were self-limited despite continued drug infusion. Distinctive cutaneous findings included scaling erythematous papules (suramin keratoses) and a predilection of many eruptions for previously sun-exposed areas. Six patients experienced severe cutaneous reactions, but no patient permanently withdrew from therapy because of cutaneous toxic reactions. Common histopathologic findings included hyperkeratosis, parakeratosis, spongiosis, acanthosis, exocytosis, apoptosis, a perivascular lymphohistiocytic infiltrate, upper dermal edema, and increased dermal mucin. Staining with S100 antigen was markedly positive in several specimens. Only trace amounts of suramin were detected in skin samples tested with high-pressure liquid chromatography. CONCLUSIONS: The incidence of cutaneous toxic reactions from suramin greatly exceeds that seen with other medications. A wide spectrum of skin manifestations were observed, including suramin keratoses and UV recall, although serious reactions were infrequent. Cutaneous toxic reactions neither predicted nor correlated with other toxic reactions from suramin. Suramin may soon become more widely used; practitioners should be aware of the high incidence and wide spectrum of cutaneous toxic reactions to this drug.

Phase I and clinical evaluation of a pharmacologically guided regimen of suramin in patients with hormone-refractory prostate cancer.

PURPOSE: This phase I study was designed with the following objectives: (1) to describe the overall and dose-limiting toxicity (DLT) of suramin administered by intermittent short intravenous infusions until DLT or disease progression; (2) to determine the ability of an adaptive control with feedback (ACF) dosing strategy to maintain suramin plasma concentrations within a preselected range; (3) to develop a population model of suramin pharmacokinetics; and (4) to identify preliminary evidence of antitumor activity. PATIENTS AND METHODS: Seventy-three patients with advanced, incurable, solid tumors (including 69 with hormone-refractory prostate cancer) received an initial 5- to 7-day daily loading treatment followed by intermittent infusions individually determined by ACF using a Bayesian algorithm and relying on population models of suramin pharmacokinetics. Treatment was given to three cohorts of patients based on target plasma suramin concentration ranges (peak, 30 minutes postsuramin, and trough on morning of the treatment day), as follows: cohort 1, 175 to 300 micrograms/mL (27 patients); cohort 2, 150 to 250 micrograms/mL (23 patients); and cohort 3, 100 to 200 micrograms/mL (23 patients). All patients were to receive suramin until DLT or disease progression. RESULTS: The DLT was most commonly seen in cohort 1 and included a syndrome of malaise and fatigue, associated with weight loss, anorexia, and changes in taste. Other reversible toxicities were neurologic, renal, cutaneous, edema, lymphopenia and anemia, ophthalmologic, and alopecia. Forty of 67 assessable patients (60%) had a 50% reduction and 25 of 67 (37%) a 75% reduction in prostate-specific antigen (PSA) levels that lasted more than 4 weeks, seven of 18 (40%) had measurable responses, and 18 of 37 (49%) demonstrated major pain improvement. The overall times to disease progression and survival were 170 and 492 days, respectively. CONCLUSION: We have characterized all toxicities with suramin in a pharmacologically guided phase I study designed to maintain plasma suramin concentrations of 100 to 300 micrograms/mL (cohorts 1 to 3). The incidence of grade 3 to 4 neurologic abnormalities was relatively low, particularly in cohorts 2 and 3 (100 to 250 micrograms/mL). Evidence of significant and durable antitumor activity was seen in all three cohorts.

Multiple eruptive dermatofibromas in an HIV-positive man.

Multiple dermatofibromas (DFs) may occur in association with altered immunity, including systemic lupus erythematosus and iatrogenic immunosuppression. We report a case of multiple eruptive DFs which occurred in a patient positive for human immunodeficiency virus (HIV). The association of eruptive DFs and HIV infection has not been previously reported. The mechanism for the development of DFs in the setting of immune disturbance remains unclear. In the setting of HIV infection, DFs may clinically mimic Kaposi's sarcoma.

Suramin, an active drug for prostate cancer: interim observations in a phase I trial.

BACKGROUND: Previous studies indicate that suramin may be an active agent for treatment of solid tumors. The clinical use of suramin is complicated by a broad spectrum of toxic effects and complex pharmacology. Studies have suggested that the dose-limiting neurotoxicity of this agent is closely related to sustained plasma drug concentrations of 350 micrograms/mL or more. PURPOSE: This phase I clinical trial in patients with solid tumors was designed to determine whether plasma concentrations resulting in both antitumor activity and manageable toxicity could be achieved with short, intermittent infusions of suramin. METHODS: Thirty-seven patients, including 33 with metastatic, hormone-refractory prostate cancer, collectively received 43 courses of suramin designed to maintain a plasma concentration range of 200-300, 175-275, or 150-250 micrograms/mL. Patients received a test dose of 200 mg and an initial loading dose of 1000 mg/m2 on day 1 of therapy. Subsequent suramin doses and schedules were individually determined using a strategy of adaptive control with feedback, which used a maximum a posteriori Bayesian algorithm to estimate individual pharmacokinetic parameters. Patients were treated until dose-limiting toxicity or progressive disease developed. RESULTS: Thirty-five of the 37 study patients and 31 of the 33 with prostate cancer were assessable for toxicity and response. Treatment was discontinued in 28 patients because of dose-limiting toxicity consisting of a syndrome of malaise, fatigue, and lethargy; recurrent reduction in creatinine clearance of 50% or more; or axonal neuropathy. Evidence of major antitumor activity was observed in patients with prostate cancer treated at all three plasma drug concentrations. Measurable responses (one complete response and five partial responses) were noted in six of 12 patients with measurable disease. Twenty-four (77%) of 31 patients had a reduction in prostate-specific antigen of 50% or more, and 17 (55%) of 31 had a reduction of 75% or more. Twenty (83%) of 24 patients reported reduction in pain. CONCLUSIONS: Suramin can be safely administered as an intermittent bolus injection by use of adaptive control with feedback to control plasma drug concentrations; toxicity is significant but manageable and reversible. Suramin is active against hormone-refractory prostate cancer. IMPLICATIONS: Future trials should address the role and necessary extent of therapeutic drug monitoring; the optimal plasma drug concentration range and duration of therapy; and the activity of suramin in combination with other agents, in earlier stages of prostate cancer, and in other tumor types.