David Farhi

Pathophysiology, etiologic factors, and clinical management of oral lichen planus, part I: facts and controversies.

Lichen planus (LP) is an inflammatory disease of the stratified squamous epithelia of unknown etiology. LP affects most frequently the oral mucosa, but it may also involve other mucosa and the skin. Oral LP (OLP) most frequently affects woman aged between 30 and 60 years. Histopathologic examination typically shows orthokeratotic hyperkeratosis, basal cell degeneration, and a dense well-defined infiltrate of lymphocytes in the superficial dermis. OLP lesions may result from the induction of keratinocytes apoptosis by cytotoxic CD8+ T cells stimulated by a yet unidentified self-antigen on a genetically predisposed patient. The association of OLP with hepatitis C virus (HCV) has been more consistently demonstrated in the Mediterranean area. Although HCV RNA and HCV-specific CD4+ and CD8+ T cells have been retrieved in the mucosal lesions of patients with chronic HCV infection and OLP, the eventual pathophysiology of HCV in OLP lesions remains unclear. Available treatments of OLP are not curative, and many have potentially prominent side effects. The objectives of OLP management should be to prevent and screen for malignant transformation and alleviate symptoms on the long-term. Avoidance of potential precipitating drugs, tobacco, alcohol, and local trauma, as well as strict oral hygiene, is essential. The first-line pharmacologic treatment relies on topical steroids. Systemic steroids should be limited to the short-term cure of severe refractory OLP. Life-long clinical follow-up, at least annually, is fundamental.

Significance of erythema nodosum and pyoderma gangrenosum in inflammatory bowel diseases: A cohort study of 2402 patients

Erythema nodosum and pyoderma gangrenosum are the most common cutaneous manifestations in inflammatory bowel diseases (IBD). We conducted the current study to assess the cumulative prevalence of erythema nodosum and pyoderma gangrenosum in patients with IBD and to appraise their association with demographic, clinical, and prognostic factors related to IBD. Between 2000 and 2005, data for all patients with IBD at our gastroenterology department were prospectively and systematically collected using a standardized protocol. Among 2402 patients (1521 diagnosed with Crohn disease [63.3%] and 744 with ulcerative colitis [31.0%]), 140 (5.8%) had atleast 1 skin manifestation. The most frequent dermatologic symptoms were erythema nodosum (4.0%) and pyoderma gangrenosum (0.75%). In multivariate analyses, erythema nodosum was significantly and independently associated with a diagnosis of Crohn disease (p < 0.001), female sex (p < 0.001), eye and joint involvement (p < 0.001), and pyoderma gangrenosum (p < 0.0001). Among patients with Crohn disease, erythema nodosum was associated with isolated colonic involvement (p = 0.0001). Pyoderma gangrenosum was significantly and independently associated with black African origin (p = 0.003), familial history of ulcerative colitis (p = 0.0005), uninterrupted pancolitis as the initial location of IBD (p = 0.03), permanent stoma (p = 0.002), eye involvement (p = 0.001), and erythema nodosum (p < 0.0001). It is noteworthy that the association between pyoderma gangrenosum and permanent stoma persisted after exclusion of patients with peristomal pyoderma gangrenosum (p = 0.07). In conclusion, neither erythema nodosum nor pyoderma gangrenosum was significantly associated with the severity criteria in IBD; however, their occurrence may reflect a peculiar phenotype among affected patients. Abbreviations: 95% CI = 95% confidence interval, EN = erythema nodosum, IBD = inflammatory bowel diseases, OR = odds ratio, PG = pyoderma gangrenosum, PSHI = Post-Surgical Handicap Index.

Non-sexually related acute genital ulcers in 13 pubertal girls: a clinical and microbiological study.

OBJECTIVE To describe the clinical and microbiological features of acute genital ulcers (AGU), which have been reported in virgin adolescents, predominantly in girls. DESIGN Descriptive study. We collected data on the clinical features, sexual history, blood cell count, biochemistry, microbiological workup, and 1-year follow-up. SETTING Departments of dermatology of 3 university hospitals in Paris. Patients Thirteen immunocompetent female patients with a first flare of non-sexually transmitted AGU. MAIN OUTCOME MEASURES Clinical and microbiological data, using a standardized form. RESULTS Mean age was 16.6 years (range, 11-19 years). Eleven patients denied previous sexual contact. A fever or flulike symptoms preceded AGU in 10 of the 13 patients (77%), with a mean delay of 3.8 days before the AGU onset (range, 0-10 days). The genital ulcers were bilateral in 10 patients. The final diagnosis was Epstein-Barr virus primary infection in 4 patients (31%) and Behçet disease in 1 patient (8%). No other infectious agents were detected in this series. CONCLUSIONS We recommend serologic testing for Epstein-Barr virus with IgM antibodies to viral capsid antigens in non-sexually related AGU in immunocompetent patients. Further microbiological studies are required to identify other causative agents.

Evaluation of a PCR Test for Detection of Treponema pallidum in Swabs and Blood

ABSTRACT Syphilis diagnosis is based on clinical observation, serological analysis, and dark-field microscopy (DFM) detection of Treponema pallidum subsp. pallidum, the etiological agent of syphilis, in skin ulcers. We performed a nested PCR (nPCR) assay specifically amplifying the tpp47 gene of T. pallidum from swab and blood specimens. We studied a cohort of 294 patients with suspected syphilis and 35 healthy volunteers. Eighty-seven of the 294 patients had primary syphilis, 103 had secondary syphilis, 40 had latent syphilis, and 64 were found not to have syphilis. The T. pallidum nPCR results for swab specimens were highly concordant with syphilis diagnosis, with a sensitivity of 82% and a specificity of 95%. Reasonable agreement was observed between the results obtained with the nPCR and DFM methods (kappa = 0.53). No agreement was found between the nPCR detection of T. pallidum in blood and the diagnosis of syphilis, with sensitivities of 29, 18, 14.7, and 24% and specificities of 96, 92, 93, and 97% for peripheral blood mononuclear cell (PBMC), plasma, serum, and whole-blood fractions, respectively. HIV status did not affect the frequency of T. pallidum detection in any of the specimens tested. Swab specimens from mucosal or skin lesions seemed to be more useful than blood for the efficient detection of the T. pallidum genome and, thus, for the diagnosis of syphilis.

Kaposi's sarcoma in HIV-negative men having sex with men.

Background:Four epidemiologic forms of Kaposis sarcoma have been described, all of which are associated with the human herpesvirus-8. In western countries, human herpesvirus-8 is more prevalent in homosexual men than in the general population, and anecdotal cases of Kaposis sarcoma in HIV-negative homosexual men have been reported. Patients and methods:We included HIV-negative homosexual and bisexual male patients with histologically proven Kaposis sarcoma in a retrospective study. Clinical data were collected using a standardized form. Risk factors for human herpesvirus-8 infection and for the development of Kaposis sarcoma were systematically recorded. Results:Between 1995 and 2007, 28 men met the defined inclusion criteria. Mean age at first symptoms of Kaposis sarcoma was 53 years. Clinical presentation resembled classical Kaposis sarcoma, with limited disease in most patients. No cellular or humoral immunodeficiency was observed. Serologic tests for human herpesvirus-8 (latent immunofluorescence assay) were positive in 88% of patients, and only two patients displayed human herpesvirus-8 viremia at the time of Kaposis sarcoma diagnosis. Three patients developed lymphoproliferative disorders (Castleman disease, follicular lymphoma and Burkitt lymphoma). In this population, α-interferon was well tolerated and gave a complete response, but most patients require only local treatment, if any. Conclusion:Kaposis sarcoma may develop in homosexual or bisexual men without HIV infection. This type of Kaposis sarcoma has clinical features in common with classical Kaposis sarcoma but occurs in younger patients. Its prognosis is good, as Kaposis sarcoma is generally limited, but clinicians should be aware of the association with lymphoproliferative diseases, which may affect prognosis.

Clinical and Serologic Baseline and Follow-Up Features of Syphilis According to HIV Status in the Post-HAART Era

There is a lack of large studies appraising the effect of the human immunodeficiency virus (HIV) on the course of syphilis since the advent of highly active antiretroviral therapy (HAART). We aimed to appraise the effect of HIV on clinical and serologic features of syphilis at baseline and during follow-up in the post-HAART era. We designed a retrospective cohort study of consecutive syphilis cases, diagnosed between 2000 and 2007, in an academic venereal disease center. Data were collected using standardized medical forms. Patients were treated according to the European guidelines. Serologic failure was defined as either a 4-fold rise in Venereal Disease Research Laboratory (VDRL) titers 30-400 days posttreatment or a lack of 4-fold drop in VDRL titers at 270-400 days posttreatment. Among 279 syphilis cases with informative baseline clinical and serologic data, HIV infection was significantly associated with men having sex with men, French origin, multiple partners, lesser usage of condom, history of sexually transmitted disease, early syphilis, anal primary chancre, and cutaneous eruption. Median baseline titer from the Treponema pallidum hemagglutination assay (TPHA) was higher in HIV-infected patients (p = 0.02). Among 144 informative syphilis cases, there was a nonsignificant trend for a lower rate of serologic response among HIV-positive patients (91.8% vs. 98.3%, p = 0.14). Serologic failure was significantly associated with a history of previous syphilis (p < 0.05). The median delay to serologic response was similar in HIV-positive (117 d) and in HIV-negative (123 d) patients (p = 0.44). We conclude that for patients under HAART treatment, the effect of HIV on serologic response to syphilis treatment is likely minimal or absent. Abbreviations: CSF = cerebrospinal fluid, FTA-abs = fluorescent treponemal antibody absorption test, HAART = highly active antiretroviral therapy, HIV = human immunodeficiency virus, HR = hazard ratio, MSM = men having sex with men, RPR = rapid plasma reagin, STD = sexually transmitted disease, TPHA = Treponema pallidum hemagglutination assay, VDRL = Venereal Disease Research Laboratory.

Predictive factors of eczema-like eruptions among patients without cutaneous psoriasis receiving Infliximab: A cohort study of 92 patients

Background: Anti-tumor-necrosis-factor-α agents are limited by their side effects. Eczema is one of the most frequent adverse reactions affecting quality of life. Objective: To assess potential predictive risk factors for eczema in patients receiving infliximab. Methods: We conducted a prospective cohort study including patients treated with infliximab for a variety of disorders with the exception of cutaneous psoriasis. Clinical features were compared among patients with and without eczema under therapy. Results: 92 consecutive patients were included; 15 developed eczema after the initiation of infliximab. In univariate analyses, a personal history of atopic symptoms was the only predictive factor for the occurrence of eczema (odds ratio = 3.6). Sex, age, principal diagnosis, dose and duration of infliximab and concomitant use of other immunosuppressors had no influence on the occurrence of eczema. Conclusions: A personal history of atopic symptoms is predictive of eczema under infliximab. Specific information should be provided to atopic patients starting such a treatment.

Terbinafine-Induced Subacute Cutaneous Lupus Erythematosus

Background: Nearly 10% of lupus erythematosus (LE) are drug induced. More than 60 different drugs are involved in iatrogenic LE. We report herein 3 cases of terbinafine-induced LE. Observations: Three patients receiving terbinafine for a suspected dermatophytic infection developed a subacute cutaneous LE, within 7 weeks following terbinafine introduction. The patients’ medical history included sicca syndrome, lung carcinoma and Kikuchi disease, respectively. Clinical remission occurred within 15 weeks following terbinafine withdrawal. Discussion: Sixteen cases of terbinafine-induced LE have been previously reported, including 13 women. The median age was 54 years. Prior autoimmunity was reported in 10 cases, including 5 pre-existing LE. The median delay between terbinafine introduction and LE onset was 5 weeks. The median time until clinical recovery following terbinafine withdrawal was 8 weeks. Conclusion: Terbinafine should be prescribed only in patients with proven dermatophytosis. We recommend cautious monitoring in patients with pre-existing autoimmunity. The diagnosis of terbinafine-induced LE should lead to the immediate and definitive withdrawal of the drug.

Management of syphilis in the HIV-infected patient: facts and controversies.

After reaching an all time low at the turn of the millennium in several industrialized countries, the syphilis incidence is rising again, perhaps as a consequence of unsafe sexual behavior in response to improved antiretroviral therapeutic options for HIV. Since the beginning of the HIV pandemic, numerous reports on the various aspects of the interaction between syphilis and HIV have been published. Controversies persist on many issues of the management of coinfected patients. This contribution presents a critical appraisal of the available literature. Few large-scale, properly designed, controlled studies have compared syphilis baseline presentation and treatment response according to HIV status. Among the weakness are (1) high rates of patients lost to follow-up, (2) lack of long-term follow-up, (3) lack of gold standard criteria for treatment response, (4) small sample size, and (5) lack of stratification according to syphilis stage, ongoing antiretroviral treatment, CD4 cell count and HIV viral load. From the available data, and given the ever-possible publication bias, we conclude that if HIV has an effect on the course of syphilis, it is small and clinically manageable in most cases. The controversial issues discussed should furnish the rational for clinical research during the forthcoming decade.

Increasing rates of quinolone-resistant Neisseria gonorrhoeae in Paris, France.

Background  Quinolone‐resistant Neisseria gonorrhoeae (QRNG) rates are increasing worldwide.