Multiple Granulomas Research Articles

Microbial exposure and autoimmunity in the etiopathogenesis of Sarcoidosis

Abstract Sarcoidosis is an enigmatic inflammatory disease affecting multiple organs such as the lungs, lymph nodes, brain, heart, and skin. It is characterized by the occurrence of multiple non-caseating granulomas comprised of macrophages, giant cells, and CD4 T cells. Although genetic and environmental factors increase the risk for sarcoidosis, the etiology remains unknown. Recent studies have shown that HLA-DR3+ sarcoidosis patients harbor CD4+ T cells reactive with a vimentin peptide 424–443. However, whether autoimmunity is a cause or consequence of the disease is not known. This study was undertaken to investigate the mechanisms responsible for activation of vimentin reactive T cells and determine their pathogenic role in sarcoidosis. For this purpose, we immunized the NOD-DR3 mice with the vimentin peptide 424–443 and induced a robust T cell response against the peptide. Fine epitope mapping using T cell hybridomas reactive with the peptide showed that both N-terminal and C-terminal amino acids were critical for T cell activation. Homology searches of microbial protein database identified a 100% homologous sequence in a protein from Klebsiella pneumoniae. Immunization of mice with this peptide, followed by intravenous transfer of peptide-coupled agarose beads induced granulomatous lesions in the lungs. Immunohistochemical analysis of these lesions showed the presence of CD4+ T cells, macrophages, and an upregulated MHC-II expression. In summary, our data demonstrate for the first time that autoimmunity is involved in the pathogenesis of sarcoidosis. Furthermore, the demonstration of molecular mimicry between a lung infecting microbe and vimentin might explain the role of microbial exposures as a risk factor for sarcoidosis.

Granuloma-like formation in deeper retinal plexus in ocular sarcoidosis.

Sarcoidosis is a multi-system disease characterized by the presence of non-caseating epithelioid granulomas in affected tissues and the most frequent cause of noninfectious uveitis in Japan. Ocular manifestations of sarcoid uveitis vary enormously and commonly characterized by granulomatous anterior uveitis, intermediate uveitis, and posterior uveitis such as retinal periphlebitis, choroiditis, optic nerve granuloma and papillitis. However, case reports of multiple granuloma formation related to sarcoid uveitis is uncommon. This report describes the use of optical coherence tomography angiography to visualize changes occurring in granuloma formation in deeper retinal plexus before and after systemic corticosteroid treatment.

SAT-491 Severe Hypercalcemia Secondary to Primary Skeletal Sarcoidosis

Introduction: Sarcoidosis is an autoimmune disorder that is characterized by non-caseating granulomas found throughout affected tissues. It has an incidence of 10-12 per 100,000 patients per year (2). Common clinical manifestations of sarcoidosis include hilar adenopathy, abnormally high angiotensin-converting enzyme (ACE), abnormally high vitamin D, and respiratory symptoms such as cough. While the lungs are commonly affected by sarcoidosis, extrapulmonary involvement occurs in over 30% of cases of sarcoidosis (1). The incidence of musculoskeletal involvement, specifically, is approximately 14%, however, most cases are asymptomatic (2). Case Presentation: A 79-year-old female with a past medical history of asthma, dementia, CAD, CKD, and HTN presents with asymptomatic hypercalcemia. She was directly admitted for hypercalcemia, AKI, and UTI and was started on Keflex and IV fluid therapy. Endocrinology, rheumatology, oncology, and nephrology were consulted. Over the course of her evaluation, further labs revealed: continued hypercalcemia: with a nadir of 13.5, elevated 1,25 vitamin D with a nadir of 100.0, and elevated ACE levels with a nadir of 125. Phosphorus, magnesium, PTH, and PTHrP levels were all within normal limits. The patient’s only complaint was dry mouth. Repeat physical examinations were stable and within normal limits other than increasing blood pressure, as high 172/70. She was started on dexamethasone to decrease conversion of Vitamin D to 1,25 hydroxyvitamin D. Throughout her stay, the patient had a negative NM parathyroid scan and a negative full body PET-CT. A CT chest w/o contrast revealed nonsp ecific ground-glass opacification with interval resolution of a small pulmonary nodule. Her diagnosis of sarcoidosis was only confirmed with a bone marrow biopsy of her right posterior iliac crest that revealed multiple non-necrotizing granulomas. Discussion: Atypical presentations of illnesses warrant exhaustive diagnostic workup. Although this patient’s laboratory values classically pointed towards a granulomatous process - elevated vitamin D and ACE levels - her diagnostic imaging studies, including full body PET-CT, were negative, steering away from a diagnosis of skeletal sarcoidosis. If it were not for a bone marrow biopsy, this patient would have potentially suffered greatly with the development of cystic bony degeneration and consequences such as fracture needing invasive orthopedic surgical intervention.

Lupus Miliaris Disseminatus Facei: An uncommon cause of Non-infectious granulomatous dermatitis

Cutaneous granulomatosis (Infectious and non-infectious) are a heterogeneous group of diseases, characterized by an inflammatory skin reaction triggered by a wide variety of stimuli, including infections, foreign bodies, malignancy, metabolites, and chemicals. We present here a rare case of multiple caseating granulomas on face of a young man who was clinically suspected to be sarcoidosis however diagnosed as Lupus Miliaris Disseminatus Facei on biopsy.

Effects of artemether on parasite burden and liver pathology in mice infected with Ibadan isolate of <i>Schistosoma mansoni</i>

This study aimed at evaluating the pathological features associated with Schistosoma mansoni infection and assessment of the efficacy of artemether in the treatment of intestinal schistosomiasis in laboratory mice. Cercariae harvested from naturally infected Biomphalaria pfeifferi obtained from Odo Ona River in Ibadan, Oyo State, Nigeria, were used to infect Swiss albino mice in the laboratory. A total of 50 mice were divided into 5 groups and artemether (300mg/kg) was administered to two of the groups at 15th and 42nd day post-infection respectively, Praziquantel (600mg/kg) was administered to a group as the control drug and another group was used as the infected control group while the last group was uninfected. Mice were sacrificed and perfused at 8th week post-infection for worm recovery, examination of the visceral organs and histopathology were conducted on liver and spleen of infected and uninfected groups. Schistosoma mansoni isolate from Ibadan, caused severe liver pathology in mice, and thus presents features indicative of epidemiological importance in human schistosomiasis. Worm burden reduction (98%) was observed in mice treated at day 15 post-infection with artemether (300 mg/kg) while 77% worm reduction was observed in the group of mice treated at day 42 post infection with artemether (300 mg/kg). Granulomas were not observed in the liver of mice treated at day 15 post-infection while those of untreated group, which had multiple granulomas. Inflammatory cellular infiltrations were observed in liver of infected mice however, the mice treated at day 15 post-infection had mild infiltration likely due to fewer eggs present in the liver. Praziquantel used as the routine control drug was less effective compared to artemether. Worm reduction (53%) was recorded for mice treated with praziquantel, gross and histopathology also revealed eggs diffusely deposited in the liver of the mice. Artemether, a derivative of artemisinin, showed a good antischistosomal effect that could be an alternative and/or complement praziquantel in the control of schistosomiasis in endemic areas.Keywords: Artemether; Schistosoma mansoni; Ibadan isolate; Swiss albino mice; gross pathology; histopathology.

A Case of Abdominal Pain Unmasking Undiagnosed Colonic Sarcoidosis

Sarcoidosis is an immune-mediated disease characterized by the presence of noncaseating granulomas. Intestinal involvement is uncommon, representing approximately 1% of all cases of sarcoidosis. Infiltration to the colon is more unique. We highlight a case of a 46 year old African American female who presented with chronic abdominal pain. A 46 year old African American female presented with intermittent left upper quadrant abdominal pain. She had no change in bowel movements or hematochezia. Review of symptoms was positive for mild shortness of breath. On physical exam, abdomen was mildly tender to palpation in the left upper quadrant. Laboratory findings were significant for low angiotensin converting enzyme level. Other biochemical testing was normal. Family history was positive for a maternal grandmother diagnosed with colon cancer at an advanced age, and a mother who was found to have polyps on routine colonoscopy. Patient was initially tried on a proton pump inhibitor with no improvement of symptoms; upper endoscopy was performed revealing superficial ulcerations and erythema. In the setting of the patient being African American over the age of 45 years old and with family history of polyps, a colonoscopy was performed. Direct visualization during colonoscopy demonstrated nodularity in patient's rectum and sigmoid colon (Figure 1). Biopsies were taken revealing multiple non-necrotizing granulomas with no glandular distortion or active inflammation in the lamina propria and glands (Figure 2). Further investigation with chest X-ray showed bilateral hilar adenopathy. The culmination of laboratory values, chest x-ray findings, and pathology results helped assist in the diagnosis of colonic sarcoidosis.1621_A Figure 1. - Nodular colonic mucosa seen on colonoscopy1621_B Figure 2. Colonic mucosa showing multiple non-necrotizing granulomas. Notice the lack of glandular distortion or active inflammation in the lamina propria and glands. The surface mucosa is also unremarkable. PAS and acid fast stains were negative. (Hematoxylin & Eosin, original magnification, x150)Sarcoidosis is rare in the intestinal tract, accounting for less than 1% of all sarcoidosis cases. A systemic review of literature by Beniwal et al. found ten total cases of colonic sarcoidosis from 1966 to 2003. Our case of sarcoidosis is unique for the rarity of disease location, the lack of pre-existing sarcoidosis, and the low serum ACE level. Diagnosis remains a challenge given nonspecific symptoms. Endoscopic findings may include nodular or friable mucosa and some lesions may be elevated, resembling a mass. Histologic examination eveals noncaseating granulomas. Treatment includes the use of corticosteroids when clinical presentation in association with biopsy results is suggestive of sarcoidosis.

Asymptomatic Transaminitis: A Case of Hepatic Sarcoidosis

Background: Sarcoidosis is a chronic inflammatory multisystem disease characterized by the presence of non-caseating granulomas. Pulmonary involvement is most common, however hepatic manifestations occur in up to 70% of cases.1 We present a patient with asymptomatic transaminitis who was found to have isolated hepatic sarcoidosis, a rare diagnosis. Case: A 47 year old female with a PMH of cholecystitis status post cholecystectomy, iron deficiency anemia and history of migraines presented for evaluation of abnormal liver enzymes. Labs were notable for AST 50-70s, ALT 60-80s, and ALP 122. She reported intermittent fevers, once a week, ranging from 99 - 101F, but denied chills or night sweats. Abdominal ultrasound and CT scan revealed peripancreatic and porta hepatis lymphadenopathy. PET scan showed increased uptake in corresponding regions. Inflammatory markers were elevated (CRP 21 and ESR 112). Hematologic work-up was unremarkable for malignancy or lymphoma. She underwent extensive serologic evaluation, which was unremarkable for autoimmune or infectious etiologies. Left lobe liver biopsy was performed after which patient started oral prednisone therapy. Biopsy results showed multiple non-caseating granulomas in portal and lobular distribution with mixed portal and periportal inflammation, as well as bile duct injury and lesions without evidence of fibrosis, steatosis, copper deposition, or stainable microorganisms. On follow-up, there was no significant improvement in transaminitis. ACE level elevated to 73. Steroids were discontinued and she is now being managed conservatively for hepatic sarcoidosis with close follow-up and discussion of long-term immunosuppressive therapy. Discussion: The etiology of sarcoidosis is still not well understood and presentations with only hepatic involvement are uncommon. This case demonstrates that isolated hepatic sarcoidosis, while a rare diagnosis, should be considered in asymptomatic patients with abnormalities in liver function tests whose preliminary laboratory and imaging work-up has been unrevealing. Serum ACE levels along with liver biopsy for histopathology provides a diagnostic clue. Management options include close medical observation, prednisone and/or ursodeoxycholic acid, as well as initiation of immunosuppressive agents.

Tuberculosis caused by Mycobacterium bovis infection in a captive-bred American bullfrog (Lithobates catesbeiana)

BackgroundTuberculosis is widely known as a progressive disease that affects endothermic animals, leading to death and/or economical losses, while mycobacterial infections in amphibians are commonly due to nontuberculous mycobacteria. To the authors’ knowledge, this report describes the first case of bovine tuberculosis in a poikilothermic animal.Case presentationAn adult female captive American bullfrog (Lithobates catesbeianus Shaw, 1802) died in a Brazilian aquarium. Multiple granulomas with acid-fast bacilli were observed in several organs. Identification of Mycobacterium bovis was accomplished by culture and PCR methods. The other animals from the same enclosure were euthanized, but no evidence of mycobacterial infection was observed.ConclusionsThe American bullfrog was introduced in several countries around the world as an alternative husbandry, and its production is purposed for zoological and aquarium collections, biomedical research, education, human consumption and pet market. The present report warns about an episode of bovine tuberculosis in an amphibian, therefore further studies are necessary to define this frog species’ role in the epidemiology of M. bovis.

Spontaneous Giant Laryngeal Granuloma in the Absence of Laryngeal Injury

The etiology of laryngeal granuloma can typically be attributed to endotracheal intubation, vocal abuse, or gastroesophageal reflux disease. There is a strong male predominance, except in cases due to intubation, where incidence is higher in women. We report a case of spontaneous development of multiple granulomas in a female with no history of intubation who presented with hoarseness and massive bilateral supraglottic masses obscuring her glottis. The disparity between the massive lesions and asymptomatic reflux highlights the need for further research in the pathophysiology of laryngeal granulomas.

ABSENCE OF ACUTE TOXICITY OF A SINGLE INTRAMUSCULAR INJECTION OF MELOXICAM IN GOLDFISH (CARASSIUS AURATUS AURATUS): A RANDOMIZED CONTROLLED TRIAL

Meloxicam is a nonsteroidal anti-inflammatory drug with preferential cyclooxygenase-2 inhibitory activity. It is frequently used in veterinary medicine, including in fish species. The efficacy and safety of meloxicam, however, has not yet been reported in adult fish. The purpose of this study was to evaluate the acute toxicity of a single intramuscular injection of meloxicam in goldfish ( Carassius auratus auratus). Following 3 wk of acclimation, 32 goldfish were randomly assigned to two groups of 16 individuals. Fish from the treatment group received a single intramuscular injection of 5 mg/kg meloxicam, while the fish from the control group received a single intramuscular injection of a 0.9% sodium chloride solution using a similar volume (1 ml/kg). No external lesions, mortality, or modifications in behavior or position in the water column were noted during the following 72 hr. Three days after the initial injection, all fish were euthanized by immersion in a solution of tricaine methanesulfonate. Complete postmortem and histologic evaluations were performed for each fish. Hemorrhage and muscular necrosis were observed at the site of injection in fish from both groups. Multiple granulomas of undetermined etiology were detected in numerous organs from fish of both groups. No statistically significant differences were detected in regard to the lesions observed in these two groups. This study demonstrates that a single intramuscular injection of meloxicam at a dosage of 5 mg/kg does not cause acute toxicity in goldfish.

The aetiology of systemic granulomatosis in meagre (Argyrosomus regius): The “Nocardia” hypothesis

One of the most important bottlenecks of meagre (Argyrosomus regius) production is Systemic Granulomatosis (SG), a pathological condition affecting the majority of farmed populations. The aetiology of the disease, which is characterized by multiple granulomas in all soft tissues, is unknown; however, two hypotheses have been raised. The first is that it may be a metabolic disorder similar to systemic granulomas observed in other cultured fishes. The second hypothesis is that it is caused by bacterial pathogens, most likely Nocardia spp. (i.e. nocardiosis). The aim of this study was to test the bacterial pathogen hypothesis as the aetiological factor of SG. Meagre from various locations of Greece were sampled and examined using microbiological, molecular and histological techniques. The prevalence of granulomas in fish was 100% and was not correlated to an infectious agent, whereas nocardiosis was found in a single incidence (prevalence: 1.3%). The results suggest that nocardiosis is not the cause of SG, as it is most probably present in a confined geographical region in Greece. The metabolic disorder hypothesis for SG is more probable and more research has to been done to conclusively identify the aetiological factor of SG.

Bile Granuloma Mimicking Peritoneal Seeding: A Case Report.

Laparoscopic cholecystectomy is a widely used treatment method for most cholelithiasis and is a relatively safe procedure. Foreign body granulomatous reaction to bile or gallstone spillage during laparoscopic cholecystectomy has rarely been reported. We report a case of bile granuloma after laparoscopic cholecystectomy, which mimicked peritoneal seeding. A 59-year-old Korean man presented with right upper quadrant pain. He underwent laparoscopic cholecystectomy for acute cholecystitis with cholelithiasis. Pathologic examination revealed an incidental adenocarcinoma invading the lamina propria with acute cholecystitis and cholelithiasis. After 3 months, follow-up abdominal computed tomography revealed a subhepatic nodule, which showed hypermetabolism on positron emission tomography–computed tomography. Suspecting localized peritoneal seeding, wedge resection of the liver, wedge resection of the transverse colon, and omentectomy were performed. Pathologic examination of the resected specimens revealed multiple bile granulomas. Awareness of bile granuloma mimicking malignancy is noteworthy for patient management to reduce unnecessary procedure during postoperative surveillance.

Mycobacterieel conjunctivaal granuloom bij een Chinese zaagbekeend (Mergus squamatus)

Een vijf jaar oude, vrouwelijke Chinese zaagbekeend werd aangeboden met een chronische en wederkerende conjunctivitis van het linkeroog. Op klinisch onderzoek werden overvloedige traanvloei en een kazig nodulair letsel vastgesteld ter hoogte van de palpebrale conjunctiva. Bij autopsie werd een kazig, necrotisch beleg waargenomen ter hoogte van de linkerconjunctiva en de infraorbitale sinus, en er waren multipele granulomen in diverse interne organen aanwezig. Histologisch onderzoek toonde granulomateuze splenitis, hepatitis, arteritis, fibrinonecrotiserende enteritis, conjunctivitis en tevens amyloïdose van lever en milt aan. Bacteriologisch en moleculair onderzoek van de conjunctiva bij het levende dier toonde respectievelijk de aanwezigheid van een multiresistente Escherichia coli en Chlamydia psittaci aan. Deze bacteriën bleken van ondergeschikt pathogeen belang. Pre mortem werd echter geen cytologisch onderzoek of ziehlneelsen (ZN)-kleuring op de histologische coupe van het conjunctivabiopt uitgevoerd. Bovendien werden pre mortem geen bijkomende onderzoeken, zoals bloedonderzoek en radiografie, uitgevoerd. De definitieve diagnose van een Mycobacterium avium-infectie ter hoogte van de conjunctiva en de inwendige organen werd pas bevestigd na autopsie door middel van een ZNkleuring en polymerasekettingreactie (PCR)- analyse. Lokale en systemische behandelingen met antimicrobiële producten, zoals fluoroquinolonen, tetracyclinen en aminoglycosiden, waren niet succesvol.

Iatrogenic Postvaccinal Injection Site Granulomas in Cattle

Background: The Brazilian government has established disease eradication and control programs to protect livestock from pathogens that affect animal health and compromise animal protein production and food safety and quality. Vaccination campaigns against foot-and-mouth disease and other infectious diseases in cattle except brucellosis can be carried out bynon-veterinarian employees. However, vaccination errors can result in the formation of granulomas at injection sites that can affect animal welfare and production. The present study aimed to report two cases of granulomas at injection sites due to the inadvertent administration of vaccines containing saponins and mineral oil as adjuvants.Cases: Case 1. The history was that a 2-year-old Devon steer was down for 7 days and was vaccinated 20 days ago with a vaccine containing saponins and mineral oil as adjuvants. Case 2. A 7-month-old Holstein heifer was examinated due to a 40-day history of ataxia, forelimb paresis progressing to tetraparesis, and vaccination with a vaccine containing saponins and mineral oil as adjuvants 60 days ago. These two animals were admitted in the Veterinary Hospital from the University of Passo Fundo (UPF) with a clinical history of incoordination and permanent decubitus after vaccination. The disease had a similar clinical course in both animals. Clinical signs included the presence of a palpable cervical mass at the site of vaccination, forelimb paresis that progressed to tetraparesis, and decubitus scars. Treatment included intravenousadministration of anti-inflammatory steroids, antibiotic therapy, daily cleansing of the pressure sores, all four limbs were massaged, animals underwent several physiotherapy sessions, slings were used to mantain recumbent patients in a standing position and supportive therapy consisted of fluid therapy and oral supplementation. Animals remained hospitalizedfor approximately 40 days. Pacients experienced temporary improvement during treatment, and would walk with an uncoordinated gait. The clinical picture worsened after treatment was discontinued, necessitating euthanasia. At necropsy, gross lesions were similar in both animals. In case 1, the trapezius was firm and pale and had multiple granulomas whichextended into the cervical vertebral column at C3-C4 and invaded the spinal canal compressing the spinal cord. In case 2, there was extensive damage to the trapezius by granulomatous inflammation; numerous nodular granulomas exuded milky contents. These lesions extended deep into the muscle fibers and infiltrated the vertebral column at C5-C6, with involvement of the medullary canal and spinal cord compression. Microscopically there was severe, diffuse pyogranulomatous myositis. Each pyogranuloma had a central clear space. Nodal architecture was effaced by these inflammatory nodules.Discussion: Some drugs and vaccines contain irritating adjuvants and induce granuloma formation at the inoculation site. In both cattle, vaccines were injected intramuscularly in the cranial third of the neck in close proximity to the cervical vertebrae and surrounding tissues. These vaccines possibly induced an exuberant inflammatory reaction at the inoculationsite. An exacerbated inflammatory response following the administration of adjuvanted vaccines by improperly trained personnel caused substantial tissue damage at the injection site. Severe, locally extensive lesions were found at necropsy affecting adjacent structures including skeletal muscles and spinal cord. The clinical signs of ataxia and forelimb paresis thatprogressed to tetraparesis were due to the marked pyogranulomatous inflammation in C3-C4 in case 1 and in C5-C6 in case 2. The present study reinforces the importance of good farming practices and properly trained personnel working at farms.Keywords: bovine, vaccine, infection site, granuloma, iatrogenic.

Presumed ocular toxocara cati infection in Port Harcourt

Toxocariasis is a zoonotic infection transmitted from animals to humans caused by parasitic round worms found in dogs and cats. Ocular toxocariasis is a rare condition caused by toxocara cati that can result in monocular loss of vision. We report an accidental finding of loss of vision in the right eye of a 39-year-old who decided to get an ocular examination following a routine prep talk in an outpatient clinic. Patient was asymptomatic and presenting best corrected visual acuity in the right eye was 6/60. Fundus examination revealed multiple discrete granulomas and a fatty liver revealed on abdominal scan. There is a positive history of living with cats while growing up. We presume this to be a case of toxocara cati. Regular ocular examinations in addition to general medical check-up should be encouraged in pet owners and those handling animals, as well as a high index of suspicion amongst ophthalmologists.

The first case of multiple pulmonary granulomas with amyloid deposition in a dental technician; a rare manifestation as an occupational lung disease

BackgroundOccupational lung diseases, such as pneumoconiosis, are one of the health problems of dental workers that have been receiving increasing interest. Pulmonary amyloidosis is a heterogenous group of diseases, and can be classified into primary (idiopathic) and secondary (associated with various inflammatory diseases, hereditary, or neoplastic). To date, the development of pulmonary amyloidosis in dental workers has not been reported.Case presentationA 58-year-old Japanese female presented with chest discomfort and low-grade fever that has persisted for 2 months. She was a dental technician but did not regularly wear a dust mask in the workplace. Chest X ray and computed tomography revealed multiple well-defined nodules in both lungs and fluorodeoxyglucose (FDG)-positron emission tomography revealed abnormal FDG uptake in the same lesions with a maximal standardized uptake value (SUV [max]) of 5.6. We next performed thoracoscopic partial resection of the lesions in the right upper and middle lobes. The histological examination of the specimens revealed granuloma formation with foreign body-type giant cells and amyloid deposition that was confirmed by Congo red staining and direct fast scarlet (DFS) staining that produce apple-green birefringence under crossed polarized light. Because there were no other causes underlying the pulmonary amyloidosis, we performed electron probe X-ray microanalysis (EPMA) of the specimens and the result showed silica deposition in the lesions. Based on these results, we finally diagnosed the patient with pulmonary granulomas with amyloid deposition caused by chronic silica exposure. Afterward, her symptoms were improved and the disease has not progressed for 2 years since proper measures against additional occupational exposure were implemented.ConclusionsOur case presented three important clinical insights: First, occupational exposure to silica in a dental workplace could be associated with the development of amyloid deposition in lung. Second, EPMA was useful to reveal the etiology of amyloid deposition in the lungs. Last, proper protection against silica is important to prevent further progression of the disease. In conclusion, our case suggested that occupational exposure to silica should be considered when amyloid deposition of unknown etiology is found in the lungs of working or retired adults.

Transbronchial lung biopsy for the diagnosis of IgG4-related lung disease.

The diagnosis of IgG4-related disease (IgG4-RD) requires a multidisciplinary approach, in which histology plays an important role. Although a diagnosis was previously established by the use of surgically resected specimens, there is increasing clinical demand to diagnose this systemic condition by the use of biopsies. The aim of the present study was to elucidate how useful transbronchial lung biopsies (TBLBs) are for this diagnostic purpose. The study cohort consisted of 20 consecutive patients diagnosed with IgG4-RD in other organs who underwent TBLB for potential pulmonary involvement. One case showing multiple granulomas suggestive of other conditions was excluded. Seven of the remaining 19 cases (37%) showed apparently normal lung tissue, indicating a sampling error, and 12 (63%) had microscopic abnormalities. Nine cases (47%) with a dense lymphoplasmacytic infiltrate met the number and ratio criteria for IgG4-positive plasma cell infiltration (>20 cells/high-power field, and an IgG4/IgG-positive plasma cell ratio of >40%). Obliterative phlebitis and storiform fibrosis were observed in one case each. In 43 control cases of various inflammatory conditions, tissue IgG4 elevations appeared to be uncommon, with only two cases (5%) each meeting the number or ratio criterion, and one case (2%) fulfilling both. All control cases with tissue IgG4 elevations were of eosinophilic pneumonia. Transbronchial lung biopsies provided histological findings that were supportive for the diagnosis of IgG4-RD in 47% of cases, with 98% diagnostic specificity. Therefore, they have potential as a useful and acceptable diagnostic approach for IgG4-related lung disease.

Miescher’s cheilitis: A case report with literature review

Miescher’s cheilitis is an inflammatory disorder characterized by chronic lip swelling due to granulomatous inflammation. It is rare disorder first described by Miescher in 1945. It is monosymptomatic form of Melkersson-Rosenthal syndrome. We report a case of Miescher’s cheilitis in a 59-year old lady presented with recurrent swelling and erythema of upper lip and submental area with no features of facial palsy and fissuring of tongue. Laboratory tests including serum complement C3, C4 and C1 esterase inhibitor functional were within normal limits. The biopsy from the upper lip revealed dermal edema, dilated lymphatic channels and multiple granulomas. After exclusion of other causes of orofacial granulomatosis, the diagnosis of Miescher’s cheilitis was made. Patient was treated with oral hydroxychloroquine and topical tacrolimus and mometasone cream with gradual improvement.

Primary actinomycosis of the right upper extremity - an unusual presentation

Actinomycosis is a chronic disease characterized by multiple abscesses, granulomas, tissue destruction, extensive fibrosis and formation of sinuses. We report a case of 45 year old female with primary cutaneous actinomycosis of right upper extremity, which is a very rare site of occurrence. The patient was treated successfully with extended period antimicrobial treatment with Doxycycline (spacing) and Cefixime.

Risk factors for laryngeal trauma and granuloma formation in pediatric intubations

ObjectiveIntubation has been associated with laryngeal injury that often resolves spontaneously without complication. We present a case of a child intubated for less than 48 hours, who presented with dysphonia and intermittent dyspnea two months after intubation due to epiglottic and vocal process granulomas. This is unusual in that multiple granulomas were found in the posterior glottis and supraglottis after short-term intubation. Our objective was to determine if there are risk factors for developing persistent post-intubation sequelae, including the delayed presentation and unusual location of post-intubation granulomas in our case. Study designCase report and systematic literature review. MethodsPubmed database, which is inclusive of MEDLINE, was used to perform a literature review with the search terms ((pediatric OR children OR neonatal OR infant) AND (laryngeal OR supraglottic) AND intubation AND (granuloma OR injury OR complication)). Only English language results were reviewed. Titles and abstracts from 379 results were reviewed. Full text was reviewed from all original studies which included human pediatric subjects and endoscopic examinations after endotracheal intubation. ResultsIn our case, laryngeal granuloma size reduced significantly after starting anti-reflux medications. The remainder was removed with laryngeal microdebrider with no recurrence at 3 weeks and 2.5 years post-operatively. Overall, 28 of the 379 studies reviewed identified evidence of laryngeal trauma due to intubation, however only 6 studies documented any type of supraglottic injury. Risk factors identified for developing post-intubation sequelae included intubation duration greater than 24 h; trauma to the larynx via various mechanisms including traumatic intubation, need for reintubation and tube changes, and increased movement while intubated; and presence of respiratory tract infection during intubation. ConclusionTrauma to the larynx during intubation should be avoided to minimize post-intubation injury in pediatric patients, by using appropriate intubation protocols, endotracheal tube size, and adequate sedation.