Association between atopic disease and vaccination granulomas: A nested case-control study.

BACKGROUND: Vaccination granulomas are observed in 1% of all children vaccinated with an aluminium-adsorbed vaccine. Most children with granulomas also have aluminium contact allergy (CA). CA and atopic diseases are both highly prevalent among children and may be associated. OBJECTIVE: To investigate the association between vaccination granulomas and atopic dermatitis (AD), asthma and rhinitis in children. METHODS: We sourced a cohort of all Danish children born from 2009 to 2017 and conducted a nested case-control study, with cases defined as children with vaccination granulomas, matched to controls 1:10 on sex, socioeconomic class, gestational age and season of birth. All cases and controls were vaccinated with aluminium-adsorbed vaccines and followed until their second birthday. We used conditional logistic regression to estimate the odds ratios (ORs). RESULTS: The study included 2171 cases with vaccination granulomas, and 21 710 controls. Children with a diagnosis of AD had a significantly higher risk of a vaccination granuloma (OR 1.50, 95% confidence intervals [CI] 1.25-1.80). No significant association was found between granulomas and asthma or rhinitis. The association between granulomas and AD was even higher in an additional sensitivity-analysis, following the children until their fourth birthday (OR 2.71, 95% CI 2.36-3.11). CONCLUSION: AD was significantly associated with vaccination granulomas, but not with other atopic diseases, within both the first 2 and 4 years of life.

Frequent Occurrence of Perianal Disease and Granuloma Formation in Patients with Crohn's Disease and Coexistent Orofacial Granulomatosis.

BACKGROUND: Orofacial granulomatosis (OFG) is an inflammatory disorder of the perioral region and oral cavity. Crohn's disease (CD) in conjunction with OFG (CD-OFG), has been suggested to constitute a phenotype of CD with distinct features at diagnosis. AIMS: The aim of this project was to investigate whether the distinct phenotypic features of CD-OFG persist in the years following the initial diagnosis of CD. METHODS: Clinical data were extracted from medical records covering the first 5 years post-diagnosis for a cohort of patients with CD-OFG, and were compared to those of references with CD without OFG. RESULTS: The clinical characteristics of our cohort of patients with CD-OFG (N = 25) were evaluated in comparison to references with CD without OFG (ratio 1:2). Five years post-diagnosis, more patients with CD-OFG had a phenotype with perianal disease (cumulative incidence: 16/25, 64% vs 13/50, 26%, P = 0.002) and intestinal granulomas (cumulative incidence: 22/25, 88% vs 24/50, 48%, P = 0.0009) than patients in the CD reference group. The patients with CD-OFG were also more likely to have undergone perianal surgery (12/25, 48% vs 4/50, 8%, P = 0.0002). At the end of the observation period, more of the patients with CD-OFG were receiving combination therapy, i.e., immunomodulators and tumor necrosis factor antagonists, than those in the CD reference group (9/25, 36% vs 5/50, 10%, P = 0.01). CONCLUSION: The results support the notion that CD in conjunction with OFG represents a specific phenotype of CD that is characterized by frequent perianal disease, pronounced intestinal granuloma formation and a need for extensive therapy.

Are Delayed Dermal Filler Granulomas More Common Since COVID-19?

PURPOSE: Granuloma and delayed inflammatory reaction to hyaluronic acid facial esthetic fillers occurs rarely. More recently, these reactions have been reported with increasing frequency and have been associated with COVID-19 infection. The purpose of the study is to determine if delayed filler granulomas are more common after the start of the COVID-19 pandemic. MATERIALS AND METHODS: A retrospective cohort study including of all patients treated with dermal filler at 4 offices of a single cosmetic surgery practice between August 1, 2018 and October 31, 2021 was performed. The primary outcome variable was granuloma formation. The primary predictor variable was time period, either pre-COVID (8/1/18 to 2/29/20) or post-COVID (3/1/20 to 10/31/21). Other study variables recorded were age, amounts of dermal fillers used, and types of dermal filler used. Data were analyzed using chi-squared test, t-tests, and logistic regression. RESULTS: Over the study period, 3,255 patients receiving 8,067 syringes of filler over 6,800 sessions were reviewed. The average patient age was 46.8 ± 13.7 years and 2,583 sessions were performed in the pre-COVID time period and 4,217 sessions in the post-COVID time period. There were 11 granulomas in 9 subjects receiving filler in the post-COVID time period and 0 granulomas in the pre-COVID time period (0.3% vs 0.0%, respectively, P = .009). Juvederm Vollure was used in 64% of patients who developed granulomas but only accounted for 26% of filler administrations in the post-COVID time period and 28% in the cohort overall (P = .02). CONCLUSIONS: Granuloma formation is a rare complication of hyaluronic acid filler injection that appears to be occurring with more frequency following the COVID-19 pandemic. Practitioners who administer dermal fillers should be aware of this complication and its apparent increased incidence.

Spectrum of cutaneous granulomatous lesions: A 5-year experience in a tertiary care centre in Sarawak.

INTRODUCTION: Granulomatous skin lesions can have various histopathological features leading to diagnostic confusion. The study aimed to determine the frequency and pattern of different granulomatous skin lesions. MATERIALS AND METHODS: This was a 5-year retrospective study done between April 2017 and March 2022 at Dermatology Department, Sarawak General Hospital. Subjects with a clinicopathological diagnosis of granulomatous diseases were included in the analysis. RESULTS: A total of 1718 skin biopsies were done during the study periods, with 49 (2.8%) confirmed granulomatous skin lesions. Most patients were aged 40-60 with a male predominance of 51%. Most of the skin biopsy samples were taken from the upper limb (36%). In this study, epitheloid granuloma was the commonest subtype (21, 43%) followed by suppurative granuloma (12, 24%), tuberculoid granuloma (8, 16%) and foreign body granuloma (5, 10%). The commonest aetiology of granulomatous skin lesions in our study was infections (30, 61%) followed by foreign body inoculation (8, 16%). Fungal infection was the most common infective cause, followed by cutaneous tuberculosis. CONCLUSION: The major cause of granulomatous dermatoses in developing countries is still infections, fungal and tuberculosis being the leading causes.

Risk factors for granulomas in children following immunization with aluminium-adsorbed vaccines: A Danish population-based cohort study.

BACKGROUND: Aluminium-adsorbed vaccines may in some children cause severely itching nodules at the injection site, known as vaccination granulomas. OBJECTIVE: To investigate vaccine-, child- and maternal-level risk factors for the development of vaccination granulomas following immunization with aluminium-adsorbed vaccines. METHODS: A Danish population-based cohort study with 553 932 children born in Denmark from 1 January 2009 to 31 December 2018, vaccinated with an aluminium-adsorbed vaccine during the first year of life, followed until 31 December 2020. Poisson regression was used to estimate granuloma rate ratios according to the type of adjuvant, accumulated dose of aluminium, timing of vaccination appointments, sex, gestational age, having siblings with granulomas, maternal age and maternal ethnicity. RESULTS: We identified 1901 vaccination granuloma cases (absolute risk, 0.34%). Among vaccine level factors, revaccination (third vs. first vaccination appointment, adjusted rate ratio [RR] 1.26, 95% confidence interval [CI] 1.03-1.55), the specific adjuvant used (aluminium phosphate vs. hydroxide, RR 0.58, 95% CI 0.48-0.70) and dosage (≥1.0 mg vs. <1.0 mg, RR 1.34, 95% CI 1.19-1.52) were associated with risk of granulomas; the timing of vaccination appointments was not. Among child-level factors, female sex (vs. males, RR 1.12, 95% CI, 1.02-1.22), prematurity (vs. term birth, RR 0.71, 95% CI, 0.54-0.93) and having sibling(s) with granulomas (vs. no siblings with granulomas, RR 46.15, 95% CI, 33.67-63.26) were associated with risk of granulomas. Among maternal-level factors, non-Danish ethnicity (vs. Danish, RR 0.51, 95% CI, 0.42-0.63) and young maternal age (<20 years vs. 20-39 years, RR 0.46, 95% CI 0.25-0.83) were associated with risk of granulomas. CONCLUSIONS: Several risk factors for vaccination granulomas at the vaccine, child and maternal levels, were identified. Reducing the dose of aluminium or replacing aluminium hydroxide with aluminium phosphate could reduce the risk of granulomas. However, this must be balanced against the potential for reduced immunogenicity.

Initial presenting manifestations in 16,486 patients with inborn errors of immunity include infections and noninfectious manifestations.

BACKGROUND: Inborn errors of immunity (IEI) are rare diseases, which makes diagnosis a challenge. A better description of the initial presenting manifestations should improve awareness and avoid diagnostic delay. Although increased infection susceptibility is a well-known initial IEI manifestation, less is known about the frequency of other presenting manifestations. OBJECTIVE: We sought to analyze age-related initial presenting manifestations of IEI including different IEI disease cohorts. METHODS: We analyzed data on 16,486 patients of the European Society for Immunodeficiencies Registry. Patients with autoinflammatory diseases were excluded because of the limited number registered. RESULTS: Overall, 68% of patients initially presented with infections only, 9% with immune dysregulation only, and 9% with a combination of both. Syndromic features were the presenting feature in 12%, 4% had laboratory abnormalities only, 1.5% were diagnosed because of family history only, and 0.8% presented with malignancy. Two-third of patients with IEI presented before the age of 6 years, but a quarter of patients developed initial symptoms only as adults. Immune dysregulation was most frequently recognized as an initial IEI manifestation between age 6 and 25 years, with male predominance until age 10 years, shifting to female predominance after age 40 years. Infections were most prevalent as a first manifestation in patients presenting after age 30 years. CONCLUSIONS: An exclusive focus on infection-centered warning signs would have missed around 25% of patients with IEI who initially present with other manifestations.

Active Margins, Plexitis, and Granulomas Increase Postoperative Crohn's Recurrence: Systematic Review and Meta-analysis.

BACKGROUND & AIMS: Rates of postoperative Crohn's disease recurrence remain high, although the ability to predict this risk of recurrence remains limited. As such, we aimed to determine the association of histologic features at the time of resection with postoperative recurrence. METHODS: Electronic databases were searched through February 2020 for studies that reported risk of clinical, endoscopic, or surgical postoperative recurrence in patients with positive resection margins, plexitis, or granulomas in the index specimen. Pooled risk ratios (RRs) with 95% CIs were calculated for this risk in patients with and without these histologic features. RESULTS: Twenty-one studies (2481 patients) assessed positive resection margins, 10 studies (808 patients) assessed plexitis, and 19 studies (1777 patients) assessed granulomas. Positive resection margins increased the risk of clinical (RR, 1.26; 95% CI, 1.06-1.49; I2 = 41%) and surgical (RR, 1.87; 95% CI, 1.14-3.08; I2 = 71%) recurrence, with a trend toward endoscopic recurrence (RR, 1.56; 95% CI, 0.79-3.05; I2 = 85%). Granulomas increased the risk of clinical (RR, 1.31; 95% CI, 1.05-1.64; I2 = 36%) and endoscopic (RR, 1.37; 95% CI, 1.00-1.87; I2 = 49%) recurrence, with a trend toward surgical recurrence (RR, 1.58; 95% CI, 0.89-2.80; I2 = 75%). Plexitis increased the risk of endoscopic recurrence (RR, 1.31; 95% CI, 1.00-1.72; I2 = 20%), with a trend toward clinical recurrence (RR, 1.34; 95% CI, 0.95-1.91; I2 = 46%). CONCLUSIONS: Positive resection margins, granulomas, and plexitis are predictive of postoperative Crohn's disease recurrence and should be recorded at the time of index resection.

Clinicopathological characteristics and aetiological factors of granulomatous gastritis.

AIMS: To examine the clinicopathological characteristics of granulomatous gastritis (GG) among different aetiologies, particularly Crohn disease (CD), and determine the contribution of Helicobacter pylori and the clinical significance of isolated GG. METHODS AND RESULTS: We identified 269 GG cases overall (0.19% prevalence): 220 had an underlying granulomatous disease (CD, sarcoidosis, tuberculosis) and only eight of these (3.6%) had H. pylori, fewer than the 10.3% rate among non-GG biopsies (P < 0.001). Conversely, among 49 GG cases without known cause (foreign body, undetermined, idiopathic), 13 (26.5%) had H. pylori more than background (P = 0.001). Most patients (n = 185/68.8%) had CD and these were more probably male (P < 0.001), younger (P < 0.001), white (P < 0.001) and had single (P = 0.010), smaller (P = 0.005) and antral (P = 0.027) granulomas amid inflammation (P = 0.005) compared to non-CD GG cases; younger age was independently associated with CD [P = 0.003; odds ratio (OR) = 1.13, 95% confidence interval (CI) = 1.04-1.22]. Among CD patients, younger age (P = 0.003; OR = 1.04, 95% CI = 1.01-1.07) and upper gastrointestinal (GI) symptoms (P = 0.017; OR = 2.53, 95% CI = 1.18-5.43) were associated with new (versus established) diagnosis, whereas multiple gastric granulomas (P = 0.003; OR = 4.67, 95% CI = 1.67-13.04) and lack of upper GI symptoms (P < 0.001; OR = 6.75, 95% CI = 2.94-15.49) were associated with lower GI granulomas. Of 86 isolated GG cases (i.e. no prior diagnosis or lower GI granulomas), 51 (59.3%) were eventually diagnosed with CD, and this was independently associated with younger age (P = 0.014; OR = 1.11, 95% CI = 1.02-1.21) and upper GI symptoms (P = 0.033; OR = 19.27, 95% CI = 1.27-293.31). The positive predictive value of finding isolated GG towards a CD diagnosis in patients aged <30 years was 91%, increasing in males (93%), with single (94%), antral (97%) granulomas or upper GI symptoms (94%). CONCLUSIONS: GG does not correlate with H. pylori in patients with granulomatous disease, but may be associated with the organism when such diagnosis is lacking. In CD patients with GG, younger age and upper GI symptoms are associated with a new CD diagnosis, whereas multiple gastric granulomas and lack of upper GI symptoms correlate with lower GI granulomas. GG, including in isolated cases with no prior clinical history or granuloma, probably signifies CD, particularly in younger, male patients or those with single, antral granulomas or upper GI symptoms.

Gastric granulomas and Helicobacter pylori: An incidental relationship.

AIMS: Studies investigating the relationship between granulomatous gastritis (GG) and Helicobacter pylori infection have been largely inconclusive. This study was designed to determine whether the analysis of a very large number of patients would provide clearer answers evaluate the association between H. pylori infection and gastric granulomas. METHODS: We used a large national database of clinicopathological data to extract 1,673,086 patients who underwent esophagogastroduodenoscopy with gastric biopsies between 2008 and 2020. In a case-control study, we evaluated the occurrence of H. pylori infection in patients with and without gastric granulomas. We also explored other clinical and histopathological associations. RESULTS: H. pylori infection was present in 44 of 496 (8.9%) patients with gastric granulomas, compared to 158,949 (9.5%) in the control group (OR = 0.93, 95% CI = 0.68-1.26). Of the 129 patients with gastric granulomas, 50 had documented inflammatory bowel disease. CONCLUSIONS: The results of this study show that the prevalence of H. pylori infection in patients with gastric granulomas is essentially identical to that of controls with no evidence of granulomas or granulomatous disease. When patients with and without a plausible-known association for gastric granulomas were analyzed separately, the prevalence of H. pylori infection remained remarkably similar in GG patients and controls. Considering the very large numbers of patients with gastric biopsies analyzed in this study, we submit that there is no basis for suggesting that H. pylori is etiologically related to GG.

Histopathological evaluation of cutaneous reactions to tattoos: Study at a tertiary care center.

BACKGROUND: Tattooing has been around for many years and is becoming an increasingly common fashion trend. As there are often few regulatory laws regarding the practice, an increase in the incidence of cutaneous reactions to tattoo inks is noted. These include allergic reactions, granulomatous dermatitis, infections, lichenoid dermatoses, and sometimes malignancy. The present study examines the histopathological changes seen in patients with cutaneous reactions to tattoo ink. METHOD: A prospective observational study was conducted over 18 months in the dermatology clinic of a tertiary care center in western India. The study population included 22 patients with cutaneous reactions over the tattoos. Punch biopsy specimens were sent to study the pattern of histopathological response. RESULTS: All 22 patients studied were between the ages of 17 and 35 years. The mean duration of development of reaction was 8.1 months. Most of the reactions were seen in black ink tattoos performed by amateurs. Perivascular and spongiotic dermatitis suggestive of allergic response was the most common feature on histopathology. Granulomatous response and lichenoid response were seen in five and three biopsies, respectively. CONCLUSION: Legalization is needed for this practice to prevent tattoo reactions. Histopathological evaluation is important as tattoo reactions may be associated with skin infections and malignancies.

Pediatric tracheostomies in patients less than 2 years of age: Analysis of complications and long-term follow-up.

PURPOSE: Identify variables that are predictive of morbidity and mortality in children under the age of two undergoing tracheostomy and to provide longitudinal data on this patient population. METHODS: Patients were retrospectively identified using Current Procedural Terminology codes 31600, 31601, 31610 from 2009 to 2016. RESULTS: Median age at time of tracheostomy was 0.43 years (interquartile range, 0.27-0.61). Patients were followed for a median of 1.39 years (range 0.03-4.25). Overall mortality rate in this cohort was 23.5% with the majority (81.3%) of deaths occurring >30 days following tracheostomy. The most frequently encountered major complication was cardiopulmonary arrest (10.29%) in the short-term follow up period (<30 days) and accidental decannulation (32.81%) during long-term follow up (>30 days). Peristomal skin breakdown was less likely to develop in patients who did not receive paralytics following tracheostomy. Most patients (54.4%) were discharged to home following initial admission and experienced a mean of 2.10 readmissions for any reason during the follow-up period. 64.4% of patients underwent surveillance direct laryngoscopy and bronchoscopy during the follow-up period and suprastomal granuloma formation was detected in 31.2% of these patients. 9 patients underwent decannulation at a median of 2 years from original tracheostomy placement. CONCLUSION: Pediatric patients under the age of 2 undergoing tracheostomy exhibit high morbidity during both the initial hospital admission and the subsequent months following discharge. However, major complications were low and mortality was not directly related to tracheostomy status in any case.

PMMA Safety for Facial Filling: Review of Rates of Granuloma Occurrence and Treatment Methods.

PMMA is composed of microspheres suspended in bovine collagen. Once injected in a dermal area, the carrier is absorbed, giving place to collagen that gives volume and maintains the spheres in the place. This process may give origin to exacerbate foreign body reaction and granuloma. The frequency of such complication is not clear. The primary objective was to review and compare the frequencies of granuloma between the published studies. The secondary aim was to compare the therapies and efficacies. The series of cases in which PMMA was used as facial filler were reviewed, and the rate of granulomas was compared; the case report studies describing those complications were also reviewed, and the therapies and outcomes were quantified. The data showed general frequency of PMMA-related complications of 4.9% and granulomas 1.9%; the incidence of granuloma was 1/2075 patients-year, and the time to development ranged from 6 to 180 months. The most used therapies were steroid, surgery or both, with satisfactory results. In conclusion, considering the actual risks and benefits of PMMA, we may affirm that it is a safe filler; doctors and patients must be conscious of potential risks when deciding for its use. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

[Rieger-Marchac flaps: Complications and patient satisfaction]. / Le lambeau de Rieger-Marchac : complications et satisfaction des patients.

PURPOSE: Like all surgical procedures, dorsal nasal flaps may be followed by both early and late complications. The aim of this study was to evaluate the surgical complications and cosmetic outcome of dorsal nasal flaps over a 7-year period in an academic dermatologic surgery unit. PATIENTS AND METHODS: Data were collected retrospectively for all patients undergoing dorsal nasal flap between 1 January 2006 and 31 December 2013. Early and late complications were recorded. Patients were contacted by phone to assess long-term outcomes. RESULTS: A total of 35 patients were included. Early complications included bleeding (n=2), local infection (n=2) and focal flap necrosis (n=1). Late complications comprised flap thickening (n=7), restriction of the medial canthus (n=2), opening of the labionasal angle (n=1), stitch granuloma (n=1) and telangiectasia on the flap (n=1). Regarding the aesthetic result, seven patients were very satisfied with the flap. Four patients underwent corrective surgery and one patient had laser treatment for telangiectasia on the flap. CONCLUSION: Two thirds of patients were satisfied with the aesthetic results and one third had late complications of the flap. Consequently, patients undergoing Rieger-Marchac procedures must be informed of the potential need for further corrective measures following nasal dorsal flap repair.

[Clinical significance of the presence of granulomas in Crohn's disease]. / Significancia clínica de la presencia de granulomas en enfermedad de Crohn.

Epithelioid granuloma is a characteristic histological feature of Crohn's disease (CD), but their significance with respect to the severity and progression of the disease is still uncertain. OBJECTIVE: To evaluate the clinical characteristics of CD patients in relation to the presence or not of granulomas in histological findings. MATERIALS AND METHODS: An observational, descriptive, retrospective study in patients diagnosed with CD from January 2004 to December 2019 in the gastroenterology department of the Guillermo Almenara Irigoyen National Hospital, Lima-Peru. RESULTS: 55 patients were included. Average age of 56 ± 8.2 years. The median time of disease was 16 months. Have two or more relapses per year (p<0.001; OR=9.75), age less than 30 years (p<0.001; OR=3.57) and a moderate to severe CDAI (≥220 points, OR=11.4, p <0.008) was significantly associated with the presence of granulomas. Severe endoscopic activity (p <0.003; OR=9.91) and the stenosing-penetrating phenotype (p<0.001; OR=22.1) also showed association with the presence of granulomas. The group of granulomas had a higher probability of corticosteroid use (p <0.024; OR=3.92) and immunomodulator (p <0.001; OR=7.10), besides the need for intestinal resection surgery (p<0.027; OR=5.07). CONCLUSIONS: The presence of granulomas in CD may be associated with increased clinical severity, endoscopic severity, immunosuppressive therapy requirement and undergo for intestinal resection.

Granulomatous interstitial nephritis on renal biopsy in human immunodeficiency virus positive patients: Prevalence and causes in Cape Town, South Africa.

South Africa continues to be burdened by human immunodeficiency virus (HIV) and tuberculosis (TB). In Cape Town, the epidemic of HIV-TB co-infection is as high as 70%. Granulomatous interstitial nephritis (GIN) has increased in frequency on renal biopsy. This study aimed to determine GIN prevalence and causes in HIV-positive patients as well as renal outcomes, patient survival and associated factors. This observational cohort study reviewed HIV-positive renal biopsies for GIN from 2005 to 2012. Causes of GIN (medications, TB, fungal and other), and baseline characteristics were analysed. A comparison of baseline data, renal function and survival was made between GIN and non-GIN cohorts. There were 45/316 biopsies demonstrating GIN. TB was the likely cause of GIN in 27 (60%) and 9 (20%) were due to a drug. Low estimated glomerular filtration rate was a statistically significant factor associated with mortality in both GIN (P = 0.045) and non-GIN cohorts (P < 0.000). In the GIN group, there were 12 (26.7%) deaths. Mortality for all patients was greatest in the first 6 months (P = 0.057). TB co-infection in both cohorts was associated with a higher mortality. The multivariate logistic regression demonstrated that a higher urine protein/creatinine ratio (uPCR) and lower estimated glomerular filtration rate were statistically associated with death. GIN is common in HIV-positive renal biopsies in Cape Town. TB-GIN was the commonest cause and associated with a high early mortality. GIN should be considered in HIV-positive patients with acute kidney injury, its presence conveys a survival benefit. There is a need for improved diagnostic accuracy and treatment strategies of TB-GIN.

Prevalence of Granulomas in Patients With Primary Immunodeficiency Disorders, United States: Data From National Health Care Claims and the US Immunodeficiency Network Registry.

PURPOSE: Granulomas are a potentially severe condition that can last for several years in persons with primary immunodeficiency disorders (PIDD). We assessed the prevalence of granulomas in patients with PIDD. METHODS: We used the Truven Health MarketScan® 2005-2015 Commercial Claims and Encounters and 2006-2015 Medicaid databases and the US Immunodeficiency Network (USIDNET) PIDD registry (a program of the Immune Deficiency Foundation). Our study population consisted of persons age < 65 years with PIDD, defined as persons with ≥ 2 claims with a diagnostic code for PIDD in MarketScan databases, or patients enrolled in USIDNET. Granulomas were identified using diagnostic codes in MarketScan or provider report in USIDNET. We calculated annual prevalence of PIDD and of granulomas among PIDD patients. RESULTS: We identified 247,474 and 40,395 persons with PIDD among commercially and Medicaid-insured persons, respectively. PIDD prevalence was 6.0/10,000 in 2005 and 11.7/10,000 in 2015 among commercially insured persons and 5.5/10,000 in 2006 and 9.6/10,000 in 2015 among Medicaid-insured persons. The prevalence of granulomas among PIDD patients was 1.2 and 1.5% among commercially and Medicaid-insured persons, respectively. In USIDNET, prevalence of granulomas was 4.4% (177/4021). The proportion with granulomas was similar across age groups in MarketScan, but varied from 2 to 9% in USIDNET. The reported prevalence of granulomas differed depending on PIDD condition: 1-2% in the MarketScan data and 0-13% in USIDNET. CONCLUSION: Granuloma prevalence in PIDD patients was 1-4%. Our study provides an estimate of the proportion of PIDD patients and suggests that granulomas are an uncommon occurrence among patients with PIDD.

Epithelioid Granulomas Associate With Increased Severity and Progression of Crohn's Disease, Based on 6-Year Follow-Up.

BACKGROUND & AIMS: Epithelioid granulomas are characteristics of a subset of patients with Crohn's disease (CD), but their significance, with regard to disease progression and severity, is unclear. We investigated the relationship between granulomas and CD severity over a 6-year time period in a large cohort of patients. METHODS: We performed a retrospective study of patients with CD seen at the Inflammatory Bowel Disease Center at the University of Pittsburgh; data were collected from 2009 through 2014 and patients were assigned to groups with and without histologic evidence of granuloma. Demographic, clinical (including disease activity, quality of life, medication use, and healthcare utilization), and laboratory data were used in association and survival analyses. Differences between groups were evaluated using the Mann-Whitney U-test for continuous variables. RESULTS: Of 1466 patients with CD, granulomas were identified in 187 (12.8%). In the subset of patients who underwent surgery, 21.0% had granulomas. The presence of granuloma was associated with increased serum levels of c-reactive protein (odds ratio [OR], 2.9; 95% CI, 2.078-4.208; P < .0001), younger mean age at diagnosis (23.6 ± 11.3 years in patients with granulomas vs 27.9 ± 13.3 years in patients without; P = .0005), higher rates of stricturing or penetrating disease phenotype, higher rates of steroid and narcotic use, and higher healthcare utilization. Among patients that underwent surgery, the presence of granulomas was associated with need for repeat surgery during the 6-year observation period (OR, 2.5; 95% CI, 1.54-4.02; P = .0002). Infliximab use was associated with detection of granuloma in a significantly lower proportion of surgical specimens compared to patients who had not been treated with a biologic agent (OR, 0.22; 95 CI, 0.05-0.97; P = .03). CONCLUSIONS: Epithelioid granulomas develop in less than 13% of patients with CD, and are associated with a more aggressive disease phenotype. Patients who have undergone surgery for CD and have granulomas are at increased risk for repeat surgery within 6 years.

Hepatic granulomas: a 17-year single tertiary centre experience.

AIMS: Hepatic granulomas have an estimated prevalence of 5% in liver biopsies, with a wide range of aetiologies globally. Our aim was to assess the clinical relevance, presenting features and underlying aetiology in a non-transplant, tertiary referral centre from a western country. METHODS AND RESULTS: This was a retrospective, single-centre review of clinical, laboratory and histological data including all adult patients for whom a liver biopsy was performed from January 1998 to December 2014. A total of 297 cases with hepatic granulomas were found in 9374 biopsies, but 57 were excluded from analysis either because they were lipogranulomas or the biopsy/aetiological work-up had not been performed at our institution. Overall, the most common aetiology was tuberculosis (35.8%), followed by primary biliary cholangitis (PBC) - 15.0%. In 30 patients (12.5%) granulomas were classified as idiopathic. From 1998 to June 2006 there were 147 granulomas in 5304 biopsies (2.8%), a frequency that did not change significantly compared to the period from July 2006 to December 2014 (93 granulomas in 4070 biopsies, 2.3%, P > 0.05). However, for the majority of cases (61.9%) there was a shift in granuloma aetiology during the former time-period that infectious diseases were responsible, whereas in the latter, autoimmune liver diseases (43%) were the main aetiology. In addition, while three cases of drug-induced granulomas were found from 1998 to June 2006, we report two cases in the second time-period. CONCLUSIONS: Hepatic granulomas can result from various infectious and non-infectious diseases. During recent years, an epidemiological shift regarding granuloma aetiology was observed, from systemic infectious diseases to non-infectious, mainly immune-mediated primary liver disorders. With an appropriate work-up the aetiology can be identified in the vast majority of cases (~90%), rendering its histological identification and characterisation essential, as disease-specific therapies are becoming available.

Prognostic significance of granulomas in children with Crohn's disease.

OBJECTIVES: Granulomas have long been considered the histological hallmark of Crohn's disease (CD). Currently, there is considerable dispute with regards to their prognostic implications. We aimed to determine the effect of granulomas on phenotypic features and disease's long-term outcomes in a large cohort of pediatric CD patients. MATERIALS AND METHODS: Medical records of pediatric CD patients diagnosed at the Schneider Children's Medical Center were reviewed retrospectively. Patients were categorized into two groups based on the presence or absence of granulomas at diagnosis. Baseline characteristics included anthropometric, clinical, laboratory, radiological and endoscopic data. Outcome measures included flares, hospitalizations, biological therapy and surgery. RESULTS: Of 289 CD patients diagnosed between 2001 and 2015, 99 patients (34%) had granulomas. Median age of the entire cohort at diagnosis was 14.2 years (females, 42.6%), with a median follow-up of 8.5 years. Patients with granulomas had a significantly higher percentage (47.5% vs. 23.7%, p = .001) of upper gastrointestinal involvement and ileo-colonic disease (64.9% vs. 49.5%, p = .01). Extraintestinal manifestations were twice as common in patients without granulomas (16.3% vs. 8.1%, p = .05). Patients with granulomas were more likely to be hospitalized (HR =1.43, 95% CI: 1.0-2.0) and to receive biologic therapy (HR = 1.52, 95% CI: 1.1-2.11). Additionally, both of these disease outcomes occurred significantly earlier (p = .013 and p = .027, respectively). In contrast, patients with granulomas did not exhibit increased risk of flares or bowel resection. CONCLUSION: Patients with granulomas exhibited a distinct phenotype at diagnosis and demonstrated a more severe disease course.

Mycobacteriosis caused by Mycobacterium marinum in reared mullets: first evidence from Sardinia (Italy).

Mycobacterium marinum is a slow-growing non-tuberculous mycobacterium, and it is considered the most common aetiologic agent of mycobacteriosis in wild and cultured fish. The diagnosis is principally made by histology when positive Ziehl-Neelsen stain granulomas are detected. The aim of this study was to investigate the occurrence of mycobacteriosis in extensively cultured Mugilidae of two lagoons (Cabras and San Teodoro) from Sardinia by the use of histology, microbiology, PCR and DNA sequencing. Nine of 106 mullets examined were affected by mycobacteriosis, and the spleen was the most affected organ. The histology detected higher rate (100%) of infection in spleen than the culture and PCR (75% and 62.5%, respectively). The sequencing of hsp65 gene identified M. marinum as the primary cause of mycobacteriosis in the mullets examined. Mullets affected by mycobacteriosis were mainly fished in the San Teodoro lagoon characterized by critical environmental conditions. Histology remains the most common method in detecting fish affected by mycobacteriosis, and PCR-based methods are essential for species identification. Our finding are worthy of attention because mycobacteriosis caused by M. marinum in reared mullets was evidenced for the first time in Sardinia, suggesting that this disease may be underestimated also in other cultured fish species.