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.

Cutaneous Sarcoidosis.

Sarcoidosis is a chronic, multisystem, inflammatory disorder that is characterized by noncaseating granulomas that cause organ dysfunction with various clinical subphenotypes. The incidence and prevalence of sarcoidosis varies greatly by ethnic background. There are significant racial disparities in prevalence, severity, and outcomes; however, there is a dearth of studies investigating the impact of structural racism. The skin is often the presenting and second most frequently involved organ with significant implications on diagnosis and management in patients with darkly pigmented skin. Workup should be comprehensive given the multisystem involvement. There are many therapies for sarcoidosis, although none is universally effective.

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.

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.

Umbilical granuloma frequency of newborns in Third-line Hospital in Turkey.

Background/Objectives: The aim is to determine the umbilical granuloma frequency of newborns and etiological factors. Methods: In this study, the records of 21344 newborns who were admitted to our hospital between February 2015 and August 2019, were examined. Results: 21191 newborns are included in the study. 2.4% of newborns was Syrian refugee and others were citizens of Turkey. Umbilical granuloma frequency was % 3.83. While umbilical granuloma frequency was 3.85% in Turkish citizen newborns, %3.01 in Syrians. Mean umbilical cord seperation time was 7.1 days in cases with umbilical granuloma. There was no statistically significant relationship determined between umbilical granuloma development and race and time of umbilical cord seperation (p >0.05) The frequency of umbilical granuloma was 3.5% for boys and 4.1% for girls. Umbilical granuloma was being observed statistically significantly higher in girls than in boys (p <0.05). 80.8% of the cases with umbilical granuloma were bathed before the umbilical cord seperation. A significant difference was determined between bathing before umbilical cord seperation and umbilical granuloma development (p < 0.05). Conclusion: Umbilical granuloma, with frequency of 3.83% in newborns. Umbilical granuloma is more common in girls and newborns bathed before the umbilical cord seperation.

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.

Changes in the clinical phenotype and behavior of pediatric luminal Crohn's disease at diagnosis in the last decade.

BACKGROUND AND AIMS: The aims of this study were to describe the trends in the behavior of pediatric CD during the last decade and to describe the seasonal variation of disease presentation. METHODS: Patients under 18 years old and diagnosed between 2009 and 2019 were included. The clinical, endoscopic, histological, and laboratory data were collected from the medical records. We analyzed the trends of these parameters according to the year and season of diagnosis. RESULTS: 654 patients were included in the study. The number of incident CD cases increased yearly. Patients diagnosed between 2015 and 2019 were younger at diagnosis (OR 2.53, p = 0.02), had more perianal diseases (OR: 2.30, p < 0.0001) and more granulomas (OR: 1.61, p = 0.003), but fewer eosinophils (OR: 0.35, p < 0.0001) and less chronic lymphoplasmacytic infiltrate (OR: 0.56, p = 0.008) as compared to the 2009-2014 cohort. There was fewer CD diagnosis during winter. Patients diagnosed in the fall had lower PCDAIs, less failure to thrive and less extensive digestive involvement. Colonic disease was significantly more frequent during summer and fall. CONCLUSION: The clinical and histological phenotype of CD has changed over time and there are important seasonal trends in the frequency and severity on disease behavior suggesting possible disease triggers.

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.

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.

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.

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.

Pediatric Ocular Toxocariasis in Costa Rica: 1998-2018 Experience.

PURPOSE: To report the epidemiology, clinical characteristics, treatment and outcomes of patients with ocular toxocariasis. METHODS: Retrospective review of patients diagnosed with ocular toxocariasis at a pediatric referral center from 1998 until 2018 in Costa Rica. RESULTS: 157 patients were diagnosed with ocular toxocariasis with a mean follow-up of 3.1 years. The mean age at presentation was 6.7 years old. The most common causes of consultation included decreased vision (29.9%), strabismus (26.7%), and leukocoria (19.7%). The most common findings included peripheral granuloma, posterior pole granuloma, and chronic endophthalmitis. Sixty-nine (43.9%) eyes had retinal detachment. Patients were managed with a variety of treatments including pars plana vitrectomy, systemic corticosteroids, anti-helminthic drugs or a combination of these. Most eyes did not exhibit functional improvement despite treatment. CONCLUSIONS: Most patients with pediatric ocular toxocariasis in Costa Rica often present late and despite treatment, most remain with poor vision in the affected eye.

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

RESUMEN Los granulomas epitelioides son hallazgos característicos de un grupo de pacientes con enfermedad de Crohn (EC), pero su significancia con respecto a la severidad y progresión de la enfermedad es aún incierta. Objetivo: Evaluar las características clínicas de los pacientes con EC en relación a la presencia o no de granulomas en los hallazgos histológicos. Materiales y métodos: Estudio observacional, descriptivo, retrospectivo en pacientes con diagnóstico de EC desde enero 2004 a diciembre 2019 en el servicio de gastroenterología del Hospital Nacional Guillermo Almenara Irigoyen, Lima-Perú. Resultados: Se incluyó 55 pacientes con media de edad de 56 ± 8,2 años. La mediana de tiempo de enfermedad fue de 16 meses. Tener dos o más recaídas al año (p<0,001; OR= 9,75), edad menor a 30 años (p<0,001; OR=3,57) y un CDAI moderado a severo (≥220 puntos, OR= 11,4; p<0,008) se asoció significativamente con la presencia de granulomas. La actividad endoscópica severa (p<0,003; OR= 9,91) y el fenotipo estenosante-penetrante (p<0,001; OR= 22,1) también mostraron asociación con la presencia de granulomas. El grupo de granulomas presentó mayor probabilidad de uso de corticoides (p<0,024; OR= 3,92) e inmunomodulador (p<0,001; OR= 7,10) además de necesidad de cirugía de resección intestinal (p< 0,027; OR: 5,07). Conclusiones: La presencia de granulomas en EC podría asociarse a mayor severidad clínica, endoscópica, requerimiento de terapia inmunosupresora y mayor necesidad de resección intestinal.

ABSTRACT 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 inflammation in lymph nodes of the head and neck-a retrospective analysis of causes in a population with very low incidence of tuberculosis.

The purpose of this study was to investigate the risk of the patient having: (1) TB, (2) sarcoidosis, (3) atypical mycobacteria, or (4) malignant disease, if FNAC or histology from a cervical lymph node shows granulomatous inflammation (GI). And to elucidate clinical characteristics associated with these causes of GI, patients with a pathological diagnosis of GI in head and neck lymph nodes were identified though a search of the Danish national pathology database. Charts were reviewed to identify the final clinical diagnosis and specific clinical characteristics. For the most common clinical diagnoses, association to clinical characteristics was analyzed using logistic regression (Odense University Hospital January 2006 to December 2015). We included 121 patients. Clinical diagnoses fell into the following categories: sarcoidosis (26%), tuberculosis (TB) (22%), cat scratch disease (6%), atypical mycobacteriosis (7%), malignancy (2%), and other (4%). In 33% of cases, the diagnosis was unknown. In the pediatric group, atypical mycobacteriosis was the most frequent clinical diagnosis (50%). TB and sarcoidosis were dependent variables in regression analysis. Characteristics significantly related to TB were histology showing necrotizing GI, gland localization in level 3-6, and origin other than Danish and TB being the tentative diagnosis. Characteristics significantly related to sarcoidosis were histology showing non-necrotizing GI, gland localization in level 3-6, the patient being of Danish origin, and unknown duration of symptoms. TB and sarcoidosis were the most common clinical diagnoses, and they were associated with specific clinical characteristics. In a third of cases, a specific clinical diagnosis was never given.

[Diagnostic difficulties of chronic pulmonary berylliosis in France]. / Difficultés diagnostiques de la bérylliose pulmonaire chronique en France.

INTRODUCTION: The epidemiology of chronic beryllium disease (CBD) in France is poorly understood. The aim of this study was to determine the number of prevalent cases of CBD in France between 2010 and 2014. METHODS: We conducted a national survey using a specific questionnaire distributed by the professional pathology services. RESULTS: In total, 33 CBD cases were reported in France, with a diagnosis established between 1982 and 2014. 85% (28/33) of CBD cases resulted from professional exposure and mostly concerned foundry workers (39%). A definite diagnosis defined by the association of an abnormal beryllium lymphocyte proliferation test and of a granulomatous inflammatory response in the lung, was obtained in 29/33 cases (88%). The other cases were probable CBD, defined by a granulomatous lung disease with a beryllium exposure, but without evidence of beryllium sensitisation. The diagnosis of granulomatous disease was confirmed a mean of 4 years after the end of exposure. The median delay between diagnosis of a granulomatous disease and diagnosis of CBD was 2 years (range 0-38 years). A genetic predisposition was found in 14 of 17 tested patients (82%). CONCLUSION: In this study, we report 33 cases of CBD followed in France between 2010 and 2014. The poor understanding of CBD and the exposure leading to it, the late development after the end of exposure, the complexity of the diagnosis and the similarities with sarcoidosis may explain the small number of cases reported.

[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.

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.