P. Morel

Clinical and biological impact of antiretroviral therapy with protease inhibitors on HIV-related Kaposi's sarcoma

Objective:To evaluate the clinical and biological impact of protease inhibitors on HIV-associated Kaposis sarcoma. Design and setting:A cohort of 10 patients included prospectively from April 1996 to June 1997 were studied in one institutional centre after initiation of protease inhibitors. Patients and methods:All patients but one (stable disease) had progressive Kaposis sarcoma. Three out of 10 patients had stopped specific chemotherapy for Kaposis sarcoma for more than 4 weeks, three were still under chemotherapy, and four had never received specific treatment of Kaposis sarcoma. Plasma HIV viral load, human herpesvirus (HHV)-8 viraemia in peripheral blood mononuclear cells (PBMC), and CD4 cell count were sequentially assessed from the beginning of therapy. For six patients, a semiquantitative evaluation of HHV-8 viral load in the Kaposis sarcoma lesions was performed during treatment using polymerase chain reaction. Results:After initiation of HIV triple therapy with protease inhibitors, we observed six complete responses, two partial responses, and two patients with progressive disease. All patients had undetectable plasma HIV viral load within 2 months of treatment. Undetectable HHV-8 viraemia in PBMC occurred in seven out of eight patients with partial or complete response and in none of the progressive patients. A decrease or negation of HHV-8 viral load in Kaposis sarcoma lesions was observed in two complete responders. Conclusion:Our results suggest that antiviral therapy with protease inhibitors are clinically efficient in HIV-associated Kaposis sarcoma and that there exists a correlation between clinical response and negation of HHV-8 viraemia.

Schönlein-Henoch Purpura in Adult Patients: Predictive Factors for IgA Glomerulonephritis in a Retrospective Study of 57 Cases

OBJECTIVES To evaluate the incidence of extracutaneous manifestations and to identify predictive factors for renal involvement in adult patients with Schönlein-Henoch purpura. DESIGN Retrospective study with a comparative analysis of patients with and without renal involvement. SETTING Patients who were attending the dermatologic department of an academic medical center. PATIENTS In patients with purpura of the lower limbs and cutaneous vascular IgA deposits for which cases were recorded from 1985 to 1993, the following selection criteria were used: age older than 15 years and absence of thrombocytopenia, of IgA deposits in the basement membrane zone, and of a known hematologic or connective tissue disorder. MAIN OUTCOME MEASURES Clinical and biological data, results of histological studies, and findings from direct immunofluorescence studies of skin biopsy specimens were compared in patients with and without renal involvement. RESULTS Fifty-seven patients were included: 23% had an IgA glomerulonephritis confirmed by results of a renal biopsy, and a further 26% showed abnormalities on urine microscopy. Joint and gastrointestinal involvement was noted in, respectively, 33% and 19% of the patients. A comparative analysis of patients with and without renal involvement failed to reveal significant differences with regard to age, sex, the presence of bullous or necrotic cutaneous lesions, gastrointestinal or joint involvement, histological features, and findings from direct immunofluorescence studies. An IgA glomerulonephritis was significantly associated with purpura above the waist (P = .03), a recent infectious history (P = .02), pyrexia (P = .01), and biological markers of inflammation (P = .006). CONCLUSIONS Despite a lower incidence of systemic involvement compared with that in other published series, the incidence of renal involvement remained high (ie, between 23% and 49%). A recent infectious history, pyrexia, the spread of purpura to the trunk, and biological markers of inflammation were predictive factors for renal involvement.

Male urethritis with and without discharge: a clinical and microbiological study.

Background: The definition of male urethritis in the absence of urethral discharge has not been well established. The sensitivity of urethral swabs and first-catch urine is controversial. Goal of this Study: To correlate clinical data (discharge or not), urethral swabs, and first-catch urine examinations with the microorganisms found within the urethra in a cohort of men attending the sexually transmitted disease clinic of Hopital Saint Louis (Paris) for treatment of urethral symptoms with or without discharge. Study Design: Two-hundred-seventy-three consecutive male patients entered this prospective study between October 1,1992 and November 30, 1992. Fifty-two patients were excluded because they had been treated with antibiotics in the previous 3 months. All patients were screened for Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, Trichomonas vaginalis, Ureaplasma urealyticum, Mycoplasma hominis, and Candida albicans. Results: Two-hundred-nineteen patients were eligible for the study (122 with discharge and 97 with no discharge). The prevalence of microorganisms was as follows: Chlamydia trachomatis in 13%, Neisseria gonorrhoeae in 11%, Ureaplasma urealyticum in 7%, Mycoplasma genitalium in 17%, Trichomonas vaginalis in 1%, and indeterminate pathogens alone in 20%. All major pathogens and Mycoplasma genitalium were more common in patients with discharge. Stratification of results according to the presence of polymorphonuclear leukocytes on the urethral swab and first-catch urine showed a low sensitivity of both tests for Chlamydia trachomatis (29%), Mycoplasma genitalium (50% and 62%), and Ureaplasma urealyticum (33%) in patients with no discharge. Conclusion: A specific and sensitive search for Chlamydia trachomatis should be done in every patient with urethral symptoms whether or not the classic symptoms of urethritis are present (discharge, presence of polymorphonuclear leukocytes in the urethra or first-catch urine).

Factors associated with underlying malignancy in a retrospective cohort of 121 patients with dermatomyositis.

Demographic, clinical, and laboratory features that predict underlying malignancy in patients with dermatomyositis (DM) are poorly known. We conducted a retrospective study in all adult patients with a definite (n = 75) or probable (n = 32) diagnosis of DM according to Bohan and Peter criteria or with amyopathic DM (n = 14) who were referred to 2 departments during a 13-year period. The diagnosis of malignancy-associated DM was retained if DM occurred in a context of recently diagnosed malignancy or if a malignancy was diagnosed during the 5 years following the diagnosis of DM. The Kaplan-Meier method was used to assess the cumulative incidence rates of underlying malignancy during the first 5 years of DM. Factors associated with malignancy in patients with DM were identified by Cox proportional hazards models. During the study period, 121 patients fulfilled the inclusion criteria (median age, 52 yr; range, 19-77 yr; women: 70%). For 29 of them, the diagnosis of malignancy-associated DM was retained. The cumulative incidence rate of malignancy was 21 ± 4% and 28 ± 5%, 1 year and 5 years after the diagnosis of DM, respectively. The median duration of follow-up of the 92 patients with no malignancy diagnosed was 36 months (range, 1-140 mo). In multivariate analysis, independent factors associated with an underlying malignancy in patients with DM were an age at diagnosis >52 years (hazard ratio [HR], 7.24; 95% confidence interval [CI], 2.35-22.31), a rapid onset of skin and/or muscular symptoms (HR, 3.11; 95% CI, 1.07-9.02), the presence of skin necrosis (HR, 3.84; 95% CI, 1.00-14.85) or periungual erythema (HR, 3.93; 95% CI, 1.16-13.24), and a low baseline level of complement factor C4 (HR, 2.74; 95% CI, 1.11-6.75). Lastly, low baseline lymphocyte count (<1500/mm3) was a protective factor of malignancy (HR, 0.33; 95% CI, 0.14-0.80). Taken together, these data may help physicians focus on a group of patients who might benefit from extensive evaluation for malignancy. Abbreviations: ALT = alanine aminotransferase, AST = aspartate aminotransferase, CI = confidence interval, CPK = creatine phosphokinase, DM = dermatomyositis, HR = hazard ratio, LDH = lactate dehydrogenase.

Prognostic Value of Quantitative Kaposi Sarcoma–Associated Herpesvirus Load in Posttransplantation Kaposi Sarcoma

Organ transplant recipients have a higher risk of Kaposi sarcoma (KS). A quantitative real-time polymerase chain reaction assay was developed to evaluate KS-associated herpesvirus (KSHV) as a prognostic tool in transplant recipients with KS. Forty-three patients who developed KS after transplantation were included in a cross-sectional study to correlate virus load with transplantation or KS parameters. Seventeen patients (40%) had KSHV viremia (>100 copies/microg of DNA; median, 6067 copies/microg of DNA). Factors associated with these levels of viremia by univariate analysis were progression of KS (P=.00002), time from KS diagnosis (P=.0007), actual stage of KS (P=.006), initial stage of KS (P=.22), graft loss (P=.013), and time from transplantation (P=.0246). Disease progression remained associated with KSHV viremia in a multivariate analysis (P=.01). Thus, quantification of KSHV load in peripheral blood mononuclear cells could represent a useful tool for monitoring transplant recipients with KS.

Analysis of alterations adjacent to invasive squamous cell carcinoma of the penis and their relationship with associated carcinoma

BACKGROUND In contrast to vulvar squamous cell carcinoma (SCC), the etiologic factors and precancerous lesions associated with penile carcinoma remain uncertain. OBJECTIVES To describe the morphologic features of lesions adjacent to invasive penile SCC and their relationship with the associated carcinoma and to compare these associations with vulvar carcinoma. METHODS This was a retrospective histologic analysis of 68 cases of penile SCC. Adjacent lesions were considered to be premalignant lesions. They were classified as penile intraepithelial neoplasia (PIN), squamous hyperplasia (SH), and lichen sclerosus (LS). PIN cases were divided into two subtypes depending on the extension of atypia throughout the epithelium and, by analogy, with the classification of the vulvar intraepithelial neoplasia (VIN). Thus they were designated as undifferentiated (or bowenoid) PIN, defined by full-thickness atypia throughout the epithelium, and differentiated PIN, characterized by atypia confined to the lower third of the epithelium. SCC subtypes were classified as usual, verrucous, warty (condylomatous), basaloid, and mixed. RESULTS Undifferentiated PIN was observed in 22 cases; LS was observed in 26 cases. Differentiated PIN and SH (except for two cases) were associated with underlying LS. Undifferentiated PIN was always associated with warty (condylomatous) (4 cases), basaloid (16 cases) or mixed SCC (2 cases), and LS with usual (19 cases) or verrucous SCC (7 cases). LIMITATIONS This was a retrospective analysis CONCLUSION This study suggests that, similarly to vulvar carcinoma, penile SCC occurs in association with two types of penile lesions: undifferentiated (or bowenoid) PIN and LS-linked differentiated PIN and/or SH. It appears that the subtype of these carcinomas is related to these adjacent lesions.

A follow‐up study in 28 patients treated with infliximab for severe recalcitrant psoriasis: evidence for efficacy and high incidence of biological autoimmunity

Background  Infliximab, an antitumour necrosis factor‐α chimeric monoclonal antibody, is effective for the treatment of severe psoriasis. While the induction of antinuclear antibodies (ANA) and antidouble‐stranded‐DNA antibodies (anti‐dsDNA‐ab) is frequently observed in patients with rheumatoid arthritis and Crohn disease receiving infliximab, the incidence of induced biological and clinical autoimmunity remains unknown in the context of psoriasis.

An Evaluation of the Polymerase Chain Reaction Amplicor Chlamydia trachomatis in Male Urine and Female Urogenital Specimens

Background and Objectives The new commercially available polymerase chain reaction (PCR)-based assay, Amplicor C. trachomatis, was compared with cell culture of C. trachomatis, for the detection of chlamydial urogenital infections. Goal of this Study To evaluate whether the Amplicor C. trachomatis PCR could improve the diagnosis of chlamydial urogenital infections, compared with cell culture of C. trachomatis considered as the reference method. Study Design A total of 466 men and 290 women attending a sexually transmitted disease (STD) clinic were tested by the Amplicor test in urine in men, and in the cervix and urethra in women, and by cell culture in the urethra of both men and women and in the cervix of the women. Results The prevalence of C. trachomatis was 13.7% by cell culture and 14.4% by the Amplicor test in men, and 3.5% by cell culture and 4.5% by the Amplicor test in women. After resolution of the discrepant results, the sensitivity of culture was 91.4% in male urethral specimens and 83.3% in endocervical and female urethral specimens. The resolved sensitivity of the PCR assay was 92.7% in male urine, 91.7% in endocervical samples, and reached 100% in testing both endocervical and female urethral specimens. Conclusion This rapid PCR-based assay showed an improvement in quality for diagnosing C. trachomatis infections.

Madurella mycetomatis mycetoma treated successfully with oral voriconazole.

SIR, Eumycetoma due to Madurella mycetomatis is a chronic, localized fungal disease endemic in some countries of Africa, the Middle East and Asia. Eumycetoma, and particularly chronic forms, require surgical debulking plus intensive antifungal treatment. This combined management is recommended by many authors but there is not yet consensus on treatment. Published results of antifungal therapy are often conflicting and therapeutic success with medical treatment alone has been very rarely reported. Here, we report a case of M. mycetomatis mycetoma successfully treated with oral voriconazole alone. A 23-year-old man from Mali, who had been in France for 1 month, presented to our department in December 1998 with a tumefaction of the right sole. The lesion, diagnosed in Mali as a mycetoma in 1992, had been surgically removed in 1997, but recovery had been incomplete. Clinical examination revealed swelling of the right sole with emission of small black grains from sinuses (Fig. 1a). Direct examination of grains in potassium hydroxide plus black chlorazol E solution confirmed the presence of fungal hyphae. Four-week cultures on Sabouraud’s dextrose agar with antibiotics (Bio-Rad, Marne la Coquette, France) at 27 C showed dark-brown colonies producing a diffusible pigment, identified as M. mycetomatis. Minimal inhibitory concentrations (MICs) of voriconazole could not be tested. Histological studies showed no grains. Magnetic resonance imaging showed extensive inflammatory lateral soft tissue involvement (5Æ5 cm long, 5 cm wide, 5 cm thick) with no signs of bone involvement (Fig. 2a). The patient received voriconazole 200 mg twice daily for 3 months, followed by 300 mg twice daily for 13 months. The lesion softened after 1 month of treatment, and a more marked improvement was noted 1 month after increasing the dose to 600 mg daily. Discharge of grains stopped after 3 months of treatment. After 4 months of treatment the lesion had shrunk to 5 cm long, 3 cm wide and 2Æ5 cm thick. After 6 months of treatment the right foot became identical to the left foot. No further lesions were noted clinically or radiologically (Fig. 2b) after 15 months of treatment. Voriconazole was well tolerated, and no adverse events occurred during the 16 months of treatment. The patient was still diseasefree 4 years after the end of treatment (Fig. 1b). Medical treatment of eumycetoma is based on ketoconazole or itraconazole. Cure or significant improvement was obtained with ketoconazole therapy (200 mg twice daily) in about 70% of patients in association or not with surgical excision. Response to itraconazole is variable due to lack of consensus on the ideal dose regimen or treatment duration: daily doses range between 50 mg and 400 mg per day, given for 6– 36 weeks. In Sudan, Hay et al. obtained less encouraging results with itraconazole than with ketoconazole: no patient given itraconazole 100 mg twice daily entered mycological and clinical remission; 42% of patients were greatly improved but 33% showed no response or deteriorated. In 25 patients treated with itraconazole and monitored for up to 12 years, Smith and Kutbi established that both medical and surgical a

Peripheral blood lymphocyte subset counts in patients with dermatomyositis clinical correlations and changes following therapy

Lymphocytopenia has been reported in patients with connective tissue diseases, including dermatomyositis (DM). However, the risk of infectious complications and the changes of lymphocytic subsets during treatment have been poorly investigated in these patients. We investigated the alterations of peripheral blood lymphocyte counts in patients with DM. A retrospective analysis was conducted in patients with an ascertained diagnosis of DM admitted from 1994 to 2000 in both departments of Dermatology of the Saint-Louis Hospital in Paris. All patients had a peripheral blood absolute lymphocyte count available before therapy. From an initial set of 63 patients, 47 were included in the study. The median absolute lymphocyte count was 888/mm3 (range, 400–4,070). Low peripheral blood CD4+ and CD8+ T-cell and B-cell counts were consistent findings (median CD4+: 382/mm3; CD8+: 211/mm3; CD19+: 122/mm3). There was a significant increase in lymphocyte count after 1 month (p < 0.0001), 3–6 months (p = 0.001), and 6–12 months (p = 0.0005) of corticosteroid treatment. Infectious events, mainly Pneumocystis carinii pneumonia (PCP), occurred in 12 patients. Their initial lymphocyte count was lower than that of patients who did not develop infections (p = 0.0001). These results support the high prevalence of lymphocytopenia in patients with DM and emphasize the risk for opportunistic infections, mainly PCP, in these patients. Further studies are warranted to evaluate the risk/benefit balance of PCP prophylaxis in patients with DM and severe lymphocytopenia.