Early-onset versus late-onset Crohn's disease: An Italian cohort study.

BACKGROUND: Disease heterogeneity, according to the age at onset, has been reported in Crohn's disease (CD). OBJECTIVE: This study aimed to compare natural history in CD patients diagnosed ≤17 (early onset (EO)) versus ≥60 (late onset (LO)) years old. METHODS: EO CD and LO CD patients referred to two Italian inflammatory bowel disease (IBD) centres were included. Relevant data comprised sex, current smoking, disease location and behaviour, IBD family history, extra-intestinal manifestations and use of medical/surgical therapy during the follow-up period. RESULTS: Among 2321 CD patients, 160 met the inclusion criteria: 92 in the EO and 68 in the LO group (mean follow-up 11.7 ± 7.7 years). Family history of IBD was more frequent in EO compared to LO CD (26% vs. 4%; p < 0.0001). Ileocolonic, upper gastrointestinal and perianal involvement occurred more frequently in EO compared to LO CD (56% vs. 21%, p < 0.0001; 17% vs. 3%, p < 0.01; and 38% vs. 19%, p < 0.01, respectively). Progression to complicated disease occurred more frequently in EO CD (40% vs. 10% p < 0.005), with an increased use of corticosteroids and anti-tumour necrosis factor alpha agents within 10 years since diagnosis (81% vs. 58%, p = 0.004, and 36% vs. 16%, p = 0.01, respectively), while the cumulative probability of surgery did not differ between the two groups. CONCLUSIONS: Patients with EO CD are more likely to develop a more aggressive disease with perianal involvement and a greater use of drug treatment compared to those with LO CD, without carrying an increased need for surgery.

Aspects of Langerhans cells and TNF-α in the cutaneous immunity of anogenital warts.

BACKGROUND: Anogenital warts are the leading sexually transmitted infection in patients seeking care at specialized clinics. They may display a vast array of forms, according to the interaction of the virus with the host's immunity. Cellular immunity is the epithelium's main form of defense against the virus, involving an active participation of the Langerhans cells and pro-inflammatory cytokines such as TNF-α. OBJECTIVE: To assess the epithelial immune response of anogenital warts in males, according to the number of lesions presented. METHODS: This is a prospective, cross-sectional study carried out at the dermatology outpatient clinic in a tertiary hospital. We included male patients over 18 years of age without comorbidities who had anogenital condylomata and no previous treatments.In order to evaluate the local epithelial immunity, the lesions were quantified, then removed and employed in CD1a immunohistochemistry assays for assessing the morphometry and morphology of Langerhans cells; TNF-α; reaction was used for determining cytokine positivity in the epithelium. RESULTS: 48 patients were included in the study. There was no statistically significant difference as to the number of Langerhans cells, in their morphology, or the presence of TNF-α. However, patients presenting with more Langerhans cells in the lesions had cells with a star-like and dendritic morphology, whereas in those with a lower cell count had cells with a rounded morphology and no dendrites (p<0.001). STUDY LIMITATIONS: Small number of patients analyzed. CONCLUSION: There was no difference in epithelial immunity between patients having few or many anogenital condyloma lesions as measured by the morphology and morphometry of Langerhans cells and TNF-α; positivity. Such an assessment employing immunity markers differing from the usual ones is expected to yield useful results.

Aspects of Langerhans cells and TNF-α in the cutaneous immunity of anogenital warts

Abstract Background: Anogenital warts are the leading sexually transmitted infection in patients seeking care at specialized clinics. They may display a vast array of forms, according to the interaction of the virus with the host's immunity. Cellular immunity is the epithelium's main form of defense against the virus, involving an active participation of the Langerhans cells and pro-inflammatory cytokines such as TNF-α. Objective: To assess the epithelial immune response of anogenital warts in males, according to the number of lesions presented. Methods: This is a prospective, cross-sectional study carried out at the dermatology outpatient clinic in a tertiary hospital. We included male patients over 18 years of age without comorbidities who had anogenital condylomata and no previous treatments.In order to evaluate the local epithelial immunity, the lesions were quantified, then removed and employed in CD1a immunohistochemistry assays for assessing the morphometry and morphology of Langerhans cells; TNF-α; reaction was used for determining cytokine positivity in the epithelium. Results: 48 patients were included in the study. There was no statistically significant difference as to the number of Langerhans cells, in their morphology, or the presence of TNF-α. However, patients presenting with more Langerhans cells in the lesions had cells with a star-like and dendritic morphology, whereas in those with a lower cell count had cells with a rounded morphology and no dendrites (p < 0.001). Study limitations: Small number of patients analyzed. Conclusion: There was no difference in epithelial immunity between patients having few or many anogenital condyloma lesions as measured by the morphology and morphometry of Langerhans cells and TNF-α; positivity. Such an assessment employing immunity markers differing from the usual ones is expected to yield useful results.

Evaluation of Patch Test Findings in Patients With Anogenital Dermatitis.

Importance: Contact dermatitis in the anogenital area is associated with sleep disturbance and dyspareunia and can profoundly affect quality of life. The literature on anogenital contact dermatitis and culprit allergens is limited. The last large-scale study on common, relevant allergens in patients with anogenital dermatitis was published in 2008. Objectives: To characterize patients with anogenital dermatitis referred for patch testing by the North American Contact Dermatitis Group, to identify common allergens, and to explore sex-associated differences between anogenital dermatitis and allergens. Design, Setting, and Participants: A retrospective, cross-sectional analysis was conducted of the North American Contact Dermatitis Group database among 28 481 patients who underwent patch testing from January 1, 2005, to December 31, 2016, at outpatient referral clinics in the United States and Canada. Exposure: Patch testing for allergens. Main Outcomes and Measures: Currently relevant allergic patch test reactions in patients with anogenital dermatitis. Results: Of 28 481 patients tested during the study period, 832 patients (336 men and 496 women; mean [SD] age, 50.1 [26.5] years) had anogenital involvement and 449 patients (177 men and 272 women; mean [SD] age, 49.6 [17.4] years) had anogenital dermatitis only. Compared with those without anogenital involvement, there were significantly more male patients in the group with anogenital dermatitis (177 [39.4%] vs 8857 of 27 649 [32.0%]; relative risk, 1.37; 95% CI, 1.14-1.66; P < .001). In the group with anogenital involvement, female patients were significantly less likely than male patients to have allergic contact dermatitis as a final diagnosis (130 [47.8%] vs 107 [60.5%]; relative risk, 0.78; 95% CI, 0.64-0.94; P = .01), whereas a final diagnosis of other dermatoses (eg, lichen planus, lichen sclerosus, or lichen simplex chronicus) was more frequent for female patients than for male patients (67 [24.6%] vs 28 [15.8%]; relative risk, 1.54; 95% CI, 1.02-2.31; P = .03). Of the 449 patients in the group with anogenital involvement only, 227 (50.6%) had 1 or more relevant reaction with patch testing. Allergens that were statistically significantly more common in patients with anogenital involvement compared with those without anogenital involvement included medicaments such as dibucaine (10 of 250 patients tested [4.0%] vs 32 of 17 494 patients tested [0.2%]; relative risk, 22.74; 95% CI, 11.05-46.78; P < .001) and preservatives such as methylchloroisothiazolinone and methylisothiazolinone (30 of 449 patients tested [6.7%] vs 1143 of 27 599 patients tested [4.1%]; relative risk, 1.61; 95% CI, 1.14-2.41; P = .008). A total of 152 patients met the definition for anogenital allergic contact dermatitis, which is defined as anogenital involvement only, allergic contact dermatitis as the only diagnosis, and 1 or more positive reaction of current clinical relevance. Conclusions and Relevance: For patients with anogenital involvement only who were referred for patch testing, male patients were more likely to have allergic contact dermatitis, whereas female patients were more likely to have other dermatoses. Common allergens or sources consisted of those likely to contact the anogenital area. For individuals with anogenital involvement suspected of having allergic contact dermatitis, reactions to preservatives, fragrances, medications (particularly topical anesthetics), and topical corticosteroids should be tested.

Human papillomavirus type 7-associated anal condyloma after renal transplantation in a child.

The prevalence, clinical significance, and spectrum of many HPV genotypes are currently largely untapped. We report a case of anal condyloma associated with a rare HPV genotype in a 11-year-old kidney transplant recipient. Eleven months post-graft, rectal bleeding revealed a 5-cm-large anal condyloma for which immuno-histopathology revealed typical papillomatosis. HPV genotyping performed on anal biopsy identified a HPV type 7, for which a single sequence was found in the GenBank sequence database. HPV7 is classically found in hand cutaneous warts, but HPV7-associated condyloma was only described in two patients. Total resection of the anal lesion was performed by electrocoagulation with no recurrence after 6 years. Post-transplant immunosuppression may promote anal condyloma with uncommon HPV types. HPV genotyping in such lesions is useful to get a better understanding of the epidemiology and clinical significance of such unusual HPV types as HPV7.

Diagnostic accuracy of faecal calprotectin in patients with active perianal fistulas.

Background: Faecal calprotectin (FC) is a marker of mucosal inflammation. Objective: The aim of this study was to determine the diagnostic accuracy of FC to (a) differentiate between perianal fistulizing Crohn's disease (pCD) and cryptoglandular perianal fistulas; and (b) detect mucosal inflammation in pCD. Methods: Patients with active perianal fistulas who had FC measured and a complete ileocolonoscopy within 10 weeks were retrospectively included. Results: Fifty-six patients were included (pCD, n = 37) of whom 19 pCD patients exhibited ulcers. FC was significantly higher in pCD compared to cryptoglandular fistulas (µg/g) (708.0 (207.0-1705.0) vs 32.0 (23.0-77.0), p < 0.001). Area-under-the-curve (AUC) value for FC receiver operating characteristic (ROC) statistics was 0.900. Optimal FC cut-off was ≥ 150 µg/g. To differentiate pCD from cryptoglandular fistulas in the absence of luminal inflammation, optimal cut-off remained ≥ 150 µg/g (AUC = 0.857, sensitivity = 0.81, specificity = 0.89, positive predictive value (PPV) = 93.8% and negative predictive value (NPV) = 70.8%). In pCD, FC was significantly increased in the presence of ulcers (1672.0 vs 238.0, p = 0.004). Optimal cut-off was ≥ 250 µg/g (AUC = 0.776; sensitivity = 0.89, specificity = 0.56, PPV - 68.0% and NPV = 83.0%). Conclusion: FC discriminates pCD from cryptoglandular fistulas, even in the absence of intestinal ulcers. In active pCD, an elevated FC does not accurately predict the presence of ulcers and should be interpreted with caution.

Hyperimmunoglobulinemia D syndrome with recurrent perianal abscess successfully treated with canakinumab.

Hyperimmunoglobulinaemia D syndrome is an autoinflammatory disease usually representing recurrent episodes of fever, arthralgia/arthritis, cervical lymphadenopathy, vomiting, diarrhoea, abdominal pain and skin rashes lasting 3-7 days every 4-8 weeks since their infancy. Recent reports suggested a link between perianal fistulae/abscess and severe colitis with hyperimmunoglobulinaemia D syndrome resembling an inflammatory bowel disease phenotype. Herein, we report an 18-month-old patient with recurrent attacks of fever and pharyngitis lasting 2-3 days every 10-15 days since the first two weeks of life. Inflammatory attacks were accompanied by diarrhoea, oral aphthous ulcers, cervical lymphadenopathy, maculopapular rash, severe leukocytosis and perianal fistulae/abscess. After the initiation of canakinumab, the patient was clinically improved with complete healing of perianal fistulas/abscesses. In conclusion, hyperimmunoglobulinaemia D syndrome should be considered in differential diagnosis of inflammatory bowel disease and recurrent perianal abscess/fistula in a patient with inflammatory attacks.

Effect of naturally acquired type-specific serum antibodies against human papillomavirus type 16 infection.

BACKGROUND: While vaccine-induced antibodies are known to confer protection against incident human papillomavirus (HPV) infection, there is inconsistent data regarding the protective effect of naturally acquired anti-HPV antibodies. OBJECTIVES: To estimate the protective effect of naturally acquired anti-HPV16 serum antibodies against incident anogenital infection with HPV16 in females aged 20-64 years and to assess whether antibodies influence the persistence/clearance of anogenital HPV16 infection. STUDY DESIGN: 4432 women attending the organized national cervical cancer screening program in Slovenia were initially enrolled. 2199 and 1848 women had valid HPV DNA results obtained using PCR-based assays and HPV antibody serotyping results obtained using pseudovirion-based serological assay, at baseline and at three-year follow-up, respectively. RESULTS: Baseline HPV16 seroprevalence was 2.4-fold higher among HPV16 DNA-positive women (55.7% vs. 23.2%; p<0.01). Baseline HPV16 DNA-positive/seronegative women frequently acquired anti-HPV16 antibodies during follow-up (OR=8.2; 95% CI: 3.8-17.8). Baseline anti-HPV16 antibodies persisted at follow-up, irrespective of baseline HPV16 DNA status (OR=40.6; 95% CI: 30.3-54.5). Baseline HPV16 DNA-negative/seropositive women were less likely to acquire HPV16 infection at follow-up (unadjusted OR=0.2; 0.1-0.9). However, the age-adjusted association was non-significant (adjusted OR=0.3; 0.1-1.2). The tendency for protective effect was stronger among women older than 25 years (OR=0.2; 0.03-1.8). Baseline anti-HPV16 antibodies were not associated with persistence/clearance of HPV16 infection at follow-up (OR=0.8; 0.3-1.9). CONCLUSIONS: Naturally acquired anti-HPV16 serum antibodies appeared to protect against anogenital HPV16 infection, but this association was at least partially confounded by age. Baseline anti-HPV16 serum antibodies did not influence persistence/clearance of HPV16 infection at follow-up.

Immunotolerant indoleamine-2,3-dioxygenase is increased in condyloma acuminata.

BACKGROUND: The tryptophan-depleting enzyme indoleamine-2,3-dioxygenase (IDO) is critical for the regulation of immunotolerance and plays an important role in immune-associated skin diseases. OBJECTIVES: To analyse the level of IDO in condyloma acuminata (CA) and its role in this condition. METHODS: IDO expression was assessed in the skin and peripheral blood of healthy controls and patients with CA. To assess the role of skin IDO in immunity, the ability of isolated epidermal cells to metabolize tryptophan and the influence on polyclonal T-cell mitogen (PHA)-stimulated T-cell proliferation were explored. RESULTS: IDO median fluorescence intensities in peripheral blood mononuclear cells from patients with CA were similar to those from healthy controls. Immunohistochemistry showed that IDO+ cells were rare in normal skin and the control skin of patients with CA, but were greatly accumulated in wart tissue. Most fluorescence signals of IDO+ cells did not overlap with those of CD1a+ Langerhans cells. Human papillomavirus (HPV) DNA probe in situ hybridization showed a large number of IDO+ cells in the HPV- site. Keratinocytes in the skin of healthy controls and the circumcised skin of patients with CA could minimally transform tryptophan into kynurenine, but IDO-competent epidermal cells from warts could transform tryptophan. In addition, these IDO-competent epidermal cells could inhibit PHA-stimulated T-cell proliferation. The addition of an IDO inhibitor, 1-methyl-d-tryptophan, restored the inhibited T-cell proliferation. CONCLUSIONS: Abnormally localized high IDO expression might be involved in the formation of a local immunotolerant microenvironment.

Anogenital Human Papillomavirus Prevalence is Unaffected by Therapeutic Tumour Necrosis Factor-alpha Inhibition.

Patients receiving tumour necrosis factor alpha (TNF-α) inhibitors are at increased risk of exacerbation of (myco-)bacterial and some viral infections. However, information on anogenital human papillomavirus (HPV) infection in these patients is sparse or conflicting. In this study 222 patients with psoriasis or inflammatory bowel disease (IBD), who received either anti-TNF-α inhibitors or alternatives (purine-, folic acid analogues, phototherapy, fumaric ester, mesalazine) continuously for at least 6 months, were evaluated for the presence of anogenital HPV-induced lesions, mucosal HPV DNA, and serological status of mucosal low-risk HPV6 and high-risk HPV16/HPV18. Hallmarks of anogenital HPV infection were more frequently detected in patients with psoriasis than in those with IBD. HPV-induced lesions, viral DNA, and seroprevalence were not elevated in participants with psoriasis or IBD, who received TNF-α inhibitors for a mean duration of 31.4 months (range 6-96 months) compared with recipients of alternative or no treatment. TNF-α blockade for a mean period of 31.4 months does not increase detectable anogenital HPV infection or disease.

Chronic granulomatous disease.

Chronic granulomatous disease is a rare inherited disorder characterised by inability of phagocytes to generate reactive oxygen species needed for intracellular killing of phagocytosed microorganisms. We report the case of an 8-month-old male child with recurrent chest infections and perianal abscess that had no response to conventional antibiotic treatment. His two elder brothers died due to similar complaints at the ages of 4 and 5 months. Four elder sisters were healthy and alive. This history indicated that the patient might have X-linked chronic granulomatous disease. A definite absence of superoxide activity in the patient's granulocytes detected by dihydrorhodamine test and nitroblue tetrazolium dye reduction test confirmed this diagnosis.

Association of HIV Infection With Anal and Penile Low-Risk Human Papillomavirus Infections Among Men Who Have Sex With Men in Amsterdam: The HIV & HPV in MSM Study.

BACKGROUND: This study among men who have sex with men (MSM) aimed to (1) assess prevalence of anogenital low-risk human papillomavirus (lrHPV) infections, (2) evaluate associations with HIV infection, and (3) investigate lrHPV concordance. METHODS: In 2010 to 2011, MSM 18 years or older were recruited in Amsterdam, the Netherlands, and provided anal and penile self-swabs (HIV & HPV in MSM study). Using the HPV SPF10-PCR/DEIA/LiPA25 system, the presence of lrHPV types 6, 11, 34, 40, 42, 43, 44, 53, 54, 66, 68/73, 70, and 74 could be detected. Logistic regression with generalized estimating equations was used to assess the independent effect of HIV on lrHPV infections. The model was repeated for lrHPV subcategories (nononcogenic and weakly oncogenic infections separately). Concordance was defined as detection of the same lrHPV type in both self-swabs of one individual. RESULTS: A total of 778 MSM were included, of whom 317 (41%) were HIV positive (median CD4 count at enrollment, 530 cells/mm). Prevalence of anal lrHPV was 45% (95% confidence interval [CI], 41%-50%) in HIV-negative MSM and 69% (95% CI, 64%-74%) in HIV-positive MSM. Prevalence of penile lrHPV was 20% (95% CI, 16%-24%) and 37% (95% CI, 31%-42%), respectively. In multivariable analysis, HIV infection was independently associated with anal (adjusted odds ratio [aOR], 1.9; 95% CI, 1.5-2.3) and penile lrHPV (aOR, 2.0; 95% CI, 1.4-2.7). Nononcogenic and weakly oncogenic lrHPV subcategories showed a similar pattern of association. Anal lrHPV infections were strongly associated with the presence of a type-concordant penile infection (aOR, 5.8; 95% CI, 4.4-7.5) and vice versa (aOR, 5.7; 95% CI, 4.4-7.5). CONCLUSIONS: Anal and penile infections with lrHPV are common in MSM. HIV infection was an independent determinant for lrHPV infections.

No evidence for a protective effect of naturally induced HPV antibodies on subsequent anogenital HPV infection in HIV-negative and HIV-infected MSM.

OBJECTIVES: To assess whether HPV serum antibodies detected after natural infection protect against subsequent anal or penile infection with the same HPV type in HIV-negative and HIV-infected men who have sex with men (MSM). METHODS: MSM aged ≥18 years were recruited in Amsterdam, the Netherlands (2010-2011), and followed-up semi-annually. Antibodies against 7 high-risk HPV types in baseline serum samples were tested using a multiplex immunoassay; baseline, 6-, and 12-month anal and penile samples were tested for HPV DNA and genotyped using the SPF10-PCR DEIA/LiPA25 system (version 1). Statistical analyses were performed using the Wei-Lin-Weissfeld method. RESULTS: 719 MSM (median age 40 years; IQR 35-48) with baseline and follow-up data were included in these analyses; 287 (40%) were HIV-infected. HPV seropositivity at baseline was not significantly associated with subsequent type-specific HPV infection at 6 or 12 months in multivariable analyses (for anal infection adjusted hazard ratio (aHR) 1.2; 95% CI 0.9-1.6; for penile infection aHR 0.8; 95% CI 0.6-1.2). High antibody concentrations showed no protective effect against subsequent infection either. CONCLUSIONS: In a population of highly sexually active, adult MSM, naturally induced HPV antibodies may not protect MSM against subsequent anal or penile HPV infection within one year.

Use of human papillomavirus vaccine in HIV-infected men for the prevention of anal dysplasia and cancer.

There are two commercially available vaccines licensed worldwide for the prevention of cervical cancer and other human papillomavirus-associated cancers such as anal cancer. However, only two countries have implemented healthcare programs that include human papillomavirus vaccination for boys and men. Although most of the human papillomavirus-related cancers in the world are attributable to cervical cancer, in developed countries anal cancer accounts for a larger proportion of human papillomavirus-related cancers. Most cases of anal cancer occur in HIV-infected men who have sex with men. In this review, we discuss the burden of human papillomavirus-related cancers in men, the most plausible immune mechanism associated with the high efficacy of the human papillomavirus vaccine, and address key issues of vaccination for HIV-infected men. Finally, we review cost-effectiveness considerations for the use of the vaccine in boys and recent guidelines for vaccination in boys, with attention to HIV-infected men.

Pharmacokinetics of daily self-application of imiquimod 3.75% cream in adult patients with external anogenital warts.

Imiquimod 3.75% cream is a new formulation intended for daily self-application. The objective of this study was to characterize serum imiquimod pharmacokinetics under maximal use conditions. Adults with ≥8 warts or total wart area ≥100 mm² applied up to 1 packet of imiquimod 3.75% cream (250 mg cream, 9.375 mg imiquimod) once daily for 3 weeks. Blood was obtained prior to doses 1, 7, 14, and 21 and at selected time points after doses 1 and 21. Eighteen patients (13 men and 5 women) with a median wart count of 16 and total wart area of 60 mm² were enrolled. Day 21 mean (SD) serum C(max) was 0.49 (0.37) ng/mL, AUC0₋24 6.80 (3.59) ng·h/mL, and t(1/2) 24.1 (12.4) hours. Steady state was achieved by day 7 with ~2-fold increase in C(max) and AUC after multiple dosing. Overall, C(max) was higher and t(max) shorter in women, with comparable AUC0₋24. Imiquimod metabolites were sporadically quantifiable. No patients discontinued for adverse events; 1 interrupted dosing for an application site ulcer. Treatment-related adverse events occurred in 16.7% of the patients. In conclusion, serum imiquimod concentrations were low after daily self-application to external anogenital warts of up to 1 packet of imiquimod 3.75% cream for 21 days.

Perianal Crohn's disease: is there something new?

Perianal lesions are common in patients with Crohn's disease, and display aggressive behavior in some cases. An accurate diagnosis is necessary for the optimal management of perianal lesions. Treatment of perianal Crohn's disease includes medical and/or surgical options. Recent discoveries in the pathogenesis of this disease have led to advances in medical and surgical therapy with good results. Perianal lesions in Crohn's disease remain a challenging aspect for both gastroenterologists and surgeons and lead to a greatly impaired quality of life for all patients affected by this disease. A multidisciplinary approach is mandatory to obtain the best results.

Autologous bone marrow-derived mesenchymal stromal cells in the treatment of fistulising Crohn's disease.

OBJECTIVE: External fistulas represent a disabling manifestation of Crohn's disease with a difficult curability and a high relapse rate despite a large therapeutic armamentarium. Stem cell therapy is a novel and promising approach for treatment of chronic inflammatory conditions. We therefore investigated the feasibility, safety and efficacy of serial intrafistular injections of autologous bone marrow-derived mesenchymal stromal cells (MSCs) in the treatment of fistulising Crohn's disease. PATIENTS AND METHODS: We enrolled 12 consecutive outpatients (eight males, median age 32 years) refractory to or unsuitable for current available therapies. MSCs were isolated from bone marrow and expanded ex vivo to be used for both therapeutic and experimental purposes. Ten patients (two refused) received intrafistular MSC injections (median 4) scheduled every 4 weeks, and were monitored by surgical, MRI and endoscopic evaluation for 12 months afterwards. The feasibility of obtaining at least 50×106 MSCs from each patient, the appearance of adverse events, and the efficacy in terms of fistula healing and reduction of both Crohn's disease and perianal disease activity indexes were evaluated. In addition, the percentage of both mucosal and circulating regulatory T cells expressing FoxP3, and the ability of MSCs to influence mucosal T cell apoptosis were investigated. RESULTS: MSC expansion was successful in all cases; sustained complete closure (seven cases) or incomplete closure (three cases) of fistula tracks with a parallel reduction of Crohn's disease and perianal disease activity indexes (p < 0.01 for both), and rectal mucosal healing were induced by treatment without any adverse effects. The percentage of mucosal and circulating regulatory T cells significantly increased during the treatment and remained stable until the end of follow up (p < 0.0001 and p < 0.01, respectively). Furthermore, MSCs have been proven to affect mucosal T cell apoptotic rate. CONCLUSIONS: Locally injected MSCs represent a feasible, safe and beneficial therapy in refractory fistulising Crohn's disease.

Anorectal Epstein-Barr virus infection mimicking Hodgkin lymphoma in an immunocompetent man.

Anorectal Hodgkin lymphoma (HL) is rare, mainly described in human immunodeficiency virus (HIV) patients with exceptional cases reported in immunocompetents. We report the case of a middle age HIV male, presenting with intestinal occlusion. Rectosigmoidoscopy showed multiple anorectal nodular and ulceronecrotic masses. The biopsy specimens revealed a diffuse polymorphous inflammatory infiltrate in the lamina propria, associated with CD30, CD20, CD3, CD15, and ALK1 scattered large Hodgkin and/or Reed Sternberg -like cells stained by LMP1 antibody and EBER. A diagnosis of EBV-associated atypical lymphoproliferative disease mimicking HL was made. These lesions remained stable for 2 years without treatment then disappeared leaving a mucosal scar. A later control biopsy showed a condylomatous lesion, without lymphoid lesion, suggesting a sexually acquired infection. Eight years later, the complete resolution of the lesion without any treatment is a strong argument against a malignant lymphoid process and raises doubts as to the reality of isolated anorectal HL in immunocompetent participants.