Hemophagocytic syndrome and metastatic melanoma: 3 cases

BACKGROUND: Macrophage activation syndrome was initially described during viral infections in immunocompromised patients. Since the original report, many diseases have been found to be associated with macrophage activation syndrome. Lymphoproliferative disorders have been more frequently reported to be associated with macrophage activation syndrome than solid tumors. We herein report three cases of macrophage activation syndrome in patients with metastatic malignant melanoma. CASE-REPORTS: Two young 32 and 40 year-old men with a liver metastatic malignant melanoma and a 62 year-old woman with a polymetastatic malignant melanoma presented a sudden deterioration of general health with hyperthermia and biological abnormalities: liver cytolysis, leucocytosis, thrombocytopenia, hypertriglyceridaemia. A fatal clinical outcome occurred rapidly despite corticotherapy and/or chemotherapy. For the first two patients the macrophage activation syndrome diagnosis was delayed because of the similarities of macrophage activation syndrome and metastatic malignant melanoma symptoms. DISCUSSION: The diagnosis of macrophage activation syndrome in patients with metastatic malignant melanoma may be difficult because of the similarities between clinical features of macrophage activation syndrome and those of metastatic malignant melanoma. Hypertriglyceridaemia is present in 60 p. 100 of macrophage activation syndrome and should lead to process a bone marrow aspirate. The search for a triggering infection should be systematically carry out because it is implicated in more than half of macrophage activation syndrome whatever the associated disease may be: neoplasia, autoimmune disease. The pathogenesis of macrophage activation syndromes occurring in patients with metastatic cancer remains unexplained. Treatment of macrophage activation syndrome is not unanimously established and usually consists in the treatment of the associated condition as well as a corticosteroid and/or an immunosuppressive treatment regimens. Prognosis of macrophage activation syndrome is usually poor especially when it is associated with a neoplasia since a fatal outcome occurs in 40 to 60 p. 100 of cases.     

Blisters and Loss of Epidermis in Patients With Lupus Erythematosus: A Clinicopathological Study of 22 Patients

The nosology of bullous lesions or equivalents (vesicles, erosions, and crusts) in patients with lupus erythematosus (LE) is rarely addressed.The primary aim of this study was to draw up a precise phenotypic inventory of such skin lesions; the secondary objective was to assess a potential relationship between the different types of loss of epidermis and extracutaneous lupus manifestations.We conducted a retrospective multicenter study including 22 patients with definite LE and bullous lesions or equivalents. All biopsies were reviewed. Patients were recruited in the dermatology departments of 6 centers. Patients were included if they met the diagnosis of systemic LE according to American College of Rheumatology and/or Systemic Lupus International Collaborating Clinics criteria or diagnosis of cutaneous LE based on classic clinical criteria and/or histological ascertainment of LE. Patients were recruited through clinician''s memory and photographic collections.Three clinico-pathological patterns could be individualized. First, toxic epidermal necrolysis (TEN)-like, sheet-like, skin detachment; sun-exposure, mild mucosal involvement, and dermal mucin deposition allow differential diagnosis with classical Lyell syndrome. Second, vesiculo-bullae and/or crusting occurring on typical lesions of subacute cutaneous lupus erythematosus or chronic cutaneous lupus erythematosus. Third, tense vesicles and/or blisters with an underlying neutrophilic dermatosis and a usual response to dapsone.A careful analysis of 22 LE patients with epidermal detachment reveals 2 main pathomechanisms: a classic LE interface dermatitis, which can be hyperacute and lead to TEN-like skin detachment; and a neutrophilic dermatosis, with tense vesicles and/or blisters, including classic bullous LE.     

Treatment of early-stage mycosis fungoides with twice-weekly applications of mechlorethamine and topical corticosteroids: a prospective study

OBJECTIVE: To determine if a therapeutic regimen of twice-weekly applications of mechlorethamine hydrochloride and betamethasone dipropionate cream is effective in the treatment of early-stage mycosis fungoides while increasing cutaneous tolerance. DESIGN: Prospective nonrandomized study conducted from November 1999 to November 2002. SETTING: Eleven university or hospital dermatology departments in France. PATIENTS: Sixty-four consecutive patients with newly diagnosed early-stage mycosis fungoides (stage IA, n = 33; stage IB, n = 26; stage IIA, n = 5). INTERVENTIONS: Patients were treated with twice-weekly applications of a 0.02% aqueous solution of mechlorethamine followed by an application of betamethasone cream during a 6-month period. MAIN OUTCOME MEASURES: The primary end point was the rate of complete response during the treatment. Secondary end points were mean delay to achieve complete response, rate of severe cutaneous reactions of intolerance, and rate of relapse after achieving complete response. RESULTS: Thirty-seven patients (58%) had a complete response after a mean +/- SD treatment duration of 3.6 +/- 2.5 months: 20 (61%) of 33 patients with stage IA disease, 15 (58%) of 26 patients with stage IB disease, and 2 (40%) of 5 patients with stage IIA disease. Eighteen patients (28%) developed severe cutaneous reactions of intolerance that necessitated treatment discontinuation. Relapse was observed in 17 patients (46%) after a mean +/- SD time of 7.7 +/- 6.5 months. CONCLUSIONS: A regimen of twice-weekly applications of mechlorethamine and betamethasone cream is an effective treatment for early-stage mycosis fungoides. The decreased frequency of applications provides an advantage to the patient by being easy to use with limited adverse effects.     

Inpatient and outpatient follow-up of grade I malignant melanoma

BACKGROUND: In 1995, the French consensus conference on management of patients with grade I malignant melanoma recommended clinical examination for patient monitoring. To date, only one survey has been conducted to evaluate these recommendations and their consequences, providing no means of assessing follow-up practices. The aim of this study was to assess follow-up practices in patients with grade I malignant melanoma followed in an outpatient private practice setting and in a hospital setting with regular appointments. PATIENTS AND METHODS: This retrospective study was conducted in collaboration with private practice and hospital dermatologists, all members of an association of continuing medical education. Medical records of 584 patients with grade I malignant melanoma who had undergone surgery between January 1, 1991 and December 31, 1995 were reviewed. Three hundred twenty-nine patients were followed in an exclusively outpatient setting by their private dermatologist and 265 were followed in a hospital setting. Follow-up data were: age, sex, date of surgical excision of the melanoma, Breslow thickness, date of each follow-up visit, presence of possible metastases and mode of diagnosis. RESULTS: Patient features were different in the two groups: mainly greater Breslow thickness and more frequent metastatic course in patients followed in a hospital setting. Among all patients, 65 (11 p. 100) developed metastases. Diagnosis of metastasis was made clinically in 95 p. 100 whatever the mode of monitoring considered. The number of patients lost to follow-up was 11p. 100 among those followed in a hospital setting and 42 p. 100 in those followed in a private practice setting. Patients lost to follow-up had a higher risk of developing metastasis as their average Breslow thickness was 1.7 mm. CONCLUSION: This study shows that patients followed in a hospital setting have a more severe prognosis than patients followed in private practice. It confirms that systematic use of complementary tests is of little interest in detecting metastases since over the period considered, the diagnosis of metastasis was made clinically in most cases. It also discloses difficulties encountered in exclusively outpatient follow-up as a high number of patients were lost to follow-up in this setting. A systematic appointment fixed by the private dermatologist during the follow-up period appears to be needed to ensure good quality follow-up. Such an appointment system should help reduce the number of patients lost to follow-up.     

Cutaneous disorders associated with hepatitis C virus infection

Since the discovery of hepatitis C virus (HCV) in 1989, many cutaneous disorders have been observed in patients suffering from chronic HCV infection. The relationship between HCV infection and cryoglobulinemia or porphyria cutanea tarda (PCT) is now clearly established, but the link between HCV and other dermatoses is still controversial. This review of the main dermatologic disorders, directly or indirectly related to HCV infection, lead to conclude that HCV markers have to be investigated systematically in case of cryoglobulinemia, PCT or pruritus. In other dermatologic disorders, HCV serology will be necessary only in case of risk factors for HCV infection, or presence of abnormal liver function tests.     

Acetaminophen protects against iron-induced cardiac damage in gerbils

There are few effective agents that safely remove excess iron from iron-overloaded individuals. Our goal was to evaluate the iron-removing effectiveness of acetaminophen given ip or orally in the gerbil iron-overload model. Male gerbils were divided into 5 groups: saline controls, iron-overloaded controls, iron-overloaded treated with ip acetaminophen, iron-overloaded treated with oral acetaminophen, and iron-overloaded treated with ipdeferoxamine. Iron dextran was injected iptwice/wk for 8 wk. Acetaminophen and deferoxamine treatments were given on Mondays, Wednesdays, and Fridays during the same 8 wk and continued for 4 wk after completion of iron-overloading. Echocardiograms were performed after completion of the iron-overloading and drug treatments. Liver and cardiac iron contents were determined by inductively coupled plasma atomic emission spectrometry (ICP-AES). Iron-overloaded controls had 232-fold and 16-fold increases in liver and cardiac iron content, respectively, compared to saline controls. In iron-overloaded controls, echocardiography showed cardiac hypertrophy, right and left ventricular distension, significant reduction in left ventricular ejection fraction (-22%), and fractional shortening (-31%) during systole. Treatments with acetaminophen (ip or oral) or deferoxamine (ip) were equally effective in reducing cardiac iron content and in preventing cardiac structural and functional changes. Both agents also significantly reduced excess hepatic iron content, although acetaminophen was less effective than deferoxamine. The results suggest that acetaminophen may be useful for treatment of iron-induced pathology.