Urocytological evaluation of pemphigus patients on long term cyclophosphamide therapy: A cross sectional study.

BACKGROUND: Cyclophosphamide therapy is associated with several urological complications including urinary bladder malignancy. Data on urologic complications of chronic cyclophosphamide therapy for dermatologic conditions is not available. OBJECTIVES: To study the urocytological profile of pemphigus patients on long-term cyclophosphamide therapy. MATERIALS AND METHODS: In a cross-sectional study, consecutive patients who had received cyclophosphamide therapy for pemphigus for more than 12 months were included. All patients were subjected to urinalysis including microscopy, culture, and urine cytology. Immunocytochemical staining for cytokeratin 20 (CK-20) on urine sediments and ELISA (enzyme-linked immunosorbent assay) for nuclear membrane protein-22 (NMP-22) were performed in all cases. In patients with urinary symptoms, microscopic hematuria, or those detected with abnormal urine sediment cytology, NMP-22, and CK-20 positivity, cystoscopy, and other relevant investigations were also done. RESULTS: A total of 44 patients (43 of pemphigus vulgaris and one of pemphigus foliaceus) were recruited. Mean duration of cyclophosphamide intake was 2.9 ± 1.7 years (range 1-8 years) with a mean cumulative dose of 53 ± 28.4 g (range 6.5-141 g). Twenty-one cases (47.7%) each were asymptomatic and symptomatic with episodic urinary symptoms [of which two had urinary tract infection (UTI)] and two patients had gross hematuria. Urine cytology revealed mild urothelial nucleomegaly with hyperchromasia in four patients. However, CK-20 and NMP-22 were negative in all samples. Cystoscopy was performed in 21 cases and did not reveal any sign of bladder malignancy. LIMITATIONS: A relatively small sample size and lack of long-term follow-up were limitations. CONCLUSIONS: In our study, no serious urologic complications were found in pemphigus cases on chronic cyclophosphamide therapy.

Current regimen of pulse therapy for pemphigus: minor modifications, improved results.

BACKGROUND: If administered properly, dexamethasone cyclophosphamide pulse (DCP) therapy has the potential to effect lifelong recovery from pemphigus. AIMS: The objective of this paper is to highlight various parameters of DCP therapy and also, to report the effects of a few modifications in the regimen. METHODS: An analysis of 123 patients treated with the DCP/DP regimen over a period of five years (1998 to 2002) is presented here. Seventeen patients who did not start/continue the treatment and three patients who died during the treatment have been excluded from the analysis. Twenty patients who had not yet started families were given only dexamethasone pulses (DPs) while 103 patients received DCPs. Low dose (50 mg/day) cyclophosphamide was used as in the standard regimen. The three modifications introduced into the regimen were: (1) an additional daily dose of oral betamethasone sufficient to control the disease activity during phase I, which was progressively tapered off completely as the patient recovered, (2) use of systemic antibiotics if the patient had skin lesions, and oral anti-candida drugs if the patient had oral ulcers until complete healing, and (3) insistence on thorough cleaning of the skin and scalp with a normal soap and shampoo, and proper maintenance of oral hygiene in spite of skin/mucosal lesions. The regimen consisted of DCP/DP repeated in exactly 28-day cycles, along with 50 mg cyclophosphamide per day, insistence on completing the treatment and avoiding irregular pulses in all patients. The number of DCPs/DPs during phase I varied in different patients depending upon the dose of betamethasone used and the rate of recovery, but phase II (nine DCPs/DPs in exactly 28-day cycles along with 50 mg cyclophosphamide per day) and phase III (only 50 mg cyclophosphamide per day) was fixed at nine months each. This was followed by posttreatment follow-up (phase IV). RESULTS: At present, all the patients are in complete remission. The confirmed period of posttreatment, disease-free follow-up period has already been more than five years in 62 patients, 3-5 years in 41 patients, 2-3 years in three patients and less than two years in six patients. Eight DCP patients and three DP patients developed a relapse (the relapse rates thus being 7.7 and 15% respectively) and received a second course of pulse therapy. They are also in remission at present. The duration of phase I was three months in 62 patients, 4-5 months in 28 patients, 6-9 months in 13, 10-12 months in nine patients and more than 12 months in 11 patients. The maximum daily dose of betamethasone used in these patients was nil in 17 patients, 1-2 mg in 85, 3-4 mg in 16, and> 4 mg in five patients. CONCLUSIONS: The modifications employed in this study could ensure the cure of all pemphigus patients by using DCP therapy administered at a private clinic.

Premature ovarian failure due to cyclophosphamide: a report of four cases in dermatology practice.

Immunosuppressant drugs like cyclophosphamide are used in the treatment of a variety of skin disorders. Though it is a very useful drug, it has some serious side-effects. Prolonged amenorrhea due to premature ovarian failure leading to infertility is one of the serious side-effects of cyclophosphamide. Four cases of cyclophosphamide-induced premature ovarian failure are presented. Two patients of scleroderma, one patient of pemphigus and one patient of hypersensitivity vasculitis developed amenorrhea due to premature ovarian failure leading to infertility after receiving cyclophosphamide 50 mg o.d. for eight months to one year. The ages of these patients ranged from 28-38 years. All these patients had good improvement of their disease with cyclophosphamide. These patients did not experience any other side-effects and their routine blood and urine tests were normal. There were no spontaneous menses during the follow-up period of one to two years. Because of the serious risk of developing premature ovarian failure, cyclophosphamide should be avoided in those patients where the family is not complete.

Granulomatose de Wegener / Wegener's granulomatosis

A granulomatose de Wegener (GW) é considerada vasculite sistêmica granulomatosa necrotizante de vasos de pequeno e médio calibres, idiopática, com envolvimento multissistêmico, geralmente afetando trato respiratório e rins. Pode ser dividida em duas formas: clássica e limitada. Nesta última inexiste comprometimento renal. Os pacientes habitualmente apresentam febre, artralgias, nódulos esparsos na pele, ulceraçäo mucosa e tosse improdutiva. Os sintomas pulmonares podem variar desde sinusites até hemorragia pulmonar difusa e insuficiência respiratória. O envolvimento renal é comumente expresso pela insuficiência renal crônica (IRC). Dados laboratoriais inespecíficos refletem alteraçöes urinárias e anemia, pela IRC, e atividade inflamatória aguda. Em contraposiçäo, considera-se o ANCA o mais específico no diagnóstico. A radiografia de tórax pode mostrar infiltrados, nódulos ou cavitaçöes pulmonares. Nas biópsias observam-se vasculite neutrofílica ou granulomatosa necrotizante, com células gigantes nos granulomas epitelióides. O tratamento com corticosteróides e imunossupressores melhorou significativamente o prognóstico da doença. Uma revisäo da clínica, da histopatologia e dos achados laboratoriais da GW é apresentada, e, particularmente, as manifestaçöes cutâneas, pulmonares e renais säo discutidas.