Family History Of Sarcoidosis Research Articles

S1671 Sarcoidosis Masquerading as Pancreatic Adenocarcinoma: A Case Report

Introduction: Sarcoidosis is a multisystem, idiopathic disease characterized by granulomatous inflammation. Symptomatic involvement of the GI tract occurs in less than 1% of cases, and of those, the stomach is most involved. Pancreatic involvement is exceedingly rare. The diagnosis of pancreatic sarcoidosis remains difficult, as pancreatic involvement may manifest as direct invasion of the organ, obstruction of the pancreatic or biliary ducts, or as a mimicker of pancreatic adenocarcinoma. We present a rare case of suspected pancreatic malignancy revealed as pancreatic sarcoid after surgical resection, in a patient without known history of sarcoidosis. Case Description/Methods: A 50-year-old male presented to the GI clinic reporting 3-4 years of epigastric pain with 30 pound weight loss. CT demonstrated a 2.6 cm mass-like lesion with infiltrative margins in the pancreatic head and uncinate process with mild biliary and pancreatic ductal dilation, highly suspicious for pancreatic adenocarcinoma. He twice underwent EUS which each revealed biliary dilatation with a mass in the head of the pancreas, with pathology showing chronic inflammation. Follow up PET scan, however, revealed a lesion in the pancreatic head that had mild FDG uptake suspicious for malignancy. Patient underwent Whipple without complication. Pathology was fortunately negative for malignancy, however revealed granulomatous inflammation in the pancreas (Figure). Findings suggestive of sarcoidosis. At follow up, patient had no evident additional manifestations of sarcoidosis. Discussion: Pancreatic involvement in sarcoidosis can manifest in many ways, including mimicking pancreatic adenocarcinoma. Given that pancreatic cancer typically portends a poor prognosis, there is greater urgency in diagnosis and treatment for suspicious pancreatic masses. A high degree of clinical suspicion is necessary to consider sarcoidosis in this setting. Our case was particularly interesting because this patient had no personal or family history of sarcoidosis and experienced no other signs or symptoms of sarcoidosis after his Whipple procedure. This patient had 2 separate EUS procedures with no evidence of malignancy, however a PET scan was concerning for pancreatic malignancy. This provided a difficult clinical circumstance, as this patient suffered from debilitating abdominal pain with no definitive diagnosis and thus no definitive treatment option. Ultimately, patient underwent Whipple procedure with relief of symptoms, and a situationally fortunate diagnosis of sarcoidosis.Figure 1.: Pathology slide revealing non-necrotizing granulomas within a peripancreatic lymph node.

CYSTIC LUNG DISEASE: AN USUAL PRESENTATION OF SP-C

TOPIC: Pediatrics TYPE: Medical Student/Resident Case Reports INTRODUCTION: Cystic interstitial lung disease (ILD) is rare in pediatrics. The differential includes genetic, congenital and acquired diseases. Often, diagnosis can be made by history and radiologic findings. However, lung biopsy and genetic testing is often necessary. CASE PRESENTATION: A 13-year-old male with PMH of asthma, allergic rhinitis (AR), eczema, chronic urticaria and no hospitalizations or surgeries was seen by an allergist for urticaria after initiation of immunotherapy. A CXR, obtained for RUL crackles heard on exam, demonstrated bilateral, R>L, upper lobe infiltrates and R hilar adenopathy. He was referred to pulmonology. Medications were Flovent and Claritin, NKDA and was a healthy term baby. No family history of asthma or CF, but mother has AR and his deceased father and paternal grandmother had sarcoidosis. No exposure to smokers, pets, carpet, farms or birds. At his pulmonology visit, repeat CXR, CBC, CMP, IgE, Aspergillus Ab, QuantiFERON gold and HP were obtained. They were normal except for the CXR, which had increased perihilar and suprahilar interstitial densities. HP panel had positive antibodies from underlying allergies. CXR prompted a chest CT which showed cystic ILD in the mid and upper lobes bilaterally with a few lesions in the lower lobes. Ground glass opacities with a honeycombing pattern were in the lung apices, but no bronchiectasis. Initial PFT showed mixed obstructive-restrictive pattern. Follow up PFT confirmed restriction, TLC 65%. DLCO mildly reduced. Normal sweat test and echo. At his bronchoscopy he complained of dyspnea on exertion. Bronchoscopy was normal. Lung biopsy showed advanced fibrotic ILD with honeycomb changes and focal dense eosinophilic aggregates, consistent with HP or surfactant deficiency. Due to dyspnea, he had pulse steroids (30mg/kg dailyx3 days), transitioned to daily steroids and weaned over 8 weeks. He was discharged with presumed diagnosis of HP, pending genetic studies. During the steroid wean, surfactant panel showed a heterozygous mutation in the surfactant protein C gene (SFTPC), c.218T>C. He was diagnosed with SP-C deficiency and started on hydroxychloroquine 400mg/day and Azithromycin 500mg 3x/week. Pulse steroids are biweekly. DISCUSSION: SP-C mutation comprises 0.36 cases per million children. Surfactant proteins A and D are involved in the immune defense and SP-B and -C prevent alveolar collapse. SP-C is a dominant condition with 55% mutations arise spontaneously. SP-C mutations are difficult to diagnose due to variability in presentation. Prognosis is variable. An interesting aspect is the family history of sarcoidosis, a disease without a definitive test. It is possible the father had SP-C deficiency and was misdiagnosed. CONCLUSIONS: This case illustrates the variable presentation of SP-C deficiency, with cystic lesions and ground glass opacities on CT. It serves as a reminder that the differential should include SP-C deficiency. REFERENCE #1: PMID: 30094155 REFERENCE #2: PMID: 24605255 REFERENCE #3: https://doi.org/10.1542/peds.2015-2725 DISCLOSURES: No relevant relationships by Emma Segal, source=Web Response No relevant relationships by Heather Staples, source=Web Response

EP22 A manifestation of severe sarcoid arthropathy in the distal interphalangeal joint

In 2011 a gentleman in his 50s presented with nasal blockage and bloody discharge. He was diagnosed with sarcoidosis and after 9 years of failed strategies to control his disease, he developed dactylitis. X-ray of the hands showed severe arthropathy in the distal interphalangeal joints. This case demonstrates an uncommon extrapulmonary manifestation of sarcoidosis. Although most of his follow up was with a respiratory clinic, his main symptoms were not due to interstitial lung disease, highlighting the importance of a multidisciplinary approach. To reduce the need for steroids, several DMARDs were tried illustrating that there are limited treatment options.

A Rare Case Study About Necrotizing Granulomatous Sarcoidosis

Sarcoidosis is a granulomatous disorder with an elusive etiology and pathogenesis. Classically, sarcoidosis is associated with non-caseating granulomas composed of mononuclear phagocytes, lymphocytes, and multinucleated giant cells. Necrotizing granulomas can also be associated with sarcoidosis but is scarcely reported in the medical literature. Necrotizing sarcoid granulomatosis is challenging to diagnose due to its rarity and similarity with other necrotizing disorders. Therefore, it is mainly considered a diagnosis of exclusion. We report one such case study, which could prompt further research to lay the course of treatment strategies for this disease. Moreover, our patient had a family history of sarcoidosis, which raises questions regarding possible genetic predisposition, and future work might help solve this medical mystery.

Sarcoidosis in donor-derived tissues after haematopoietic stem cell transplantation

To the Editor: This is the first case of sarcoidosis in donor-derived tissues, confirmed by fluorescence in situ hybridisation (FISH), after haematopoietic stem cell transplantation (HSCT). A 64-year-old Japanese female was diagnosed to have adult T-cell leukaemia in December 2009. She had neither any past history nor a family history of sarcoidosis. She underwent HSCT (unrelated bone marrow transplantation) in May 2010, after receiving treatment with fludarabine, busulfan, and total body irradiation, from a human leukocyte antigen (HLA)-matched male donor who had no history of sarcoidosis. Although no lung involvement was seen in the early phase after HSCT, she was complicated by cytomegalovirus viraemia and acute graft versus host disease (GVHD), which required ganciclovir, systemic steroids and tacrolimus hydrate. She had achieved a negative proviral load of human T-cell lymphocytic virus (HTLV)-1 in her peripheral blood, 3 months after the transplant. At that time, the patient did not show any skin or eye symptoms or liver dysfunction, which are symptoms that are often seen in patients with chronic GVHD. A subcutaneous mass developed on her left upper arm in September 2011 (16 months after the transplant), although the proviral load of HTLV-1 remained negative. Fluorodeoxyglucose positron emission tomography (FDG-PET) or computed tomography (CT) imaging showed FDG accumulations in the mediastinal and hilar lymphadenopathy, in addition to the mass lesion located on the left upper arm. Although …

Bilateral hilar lymphadenopathy due to Chlamydia pneumoniae infection

We here report a 5-year-old boy who presented with cough and bilateral hilar lymphadenopathy with a family history of sarcoidosis. The laboratory investigations did not confirm this diagnosis. The child was serologically proven to have Chlamydia pneumoniae infection. He responded well to a course of erythromycin resulting in complete resolution of his symptoms and the presenting radiographic findings on his initial chest X-ray. Pediatr. Pulmonol. 2011; 46:1038-1040. © 2011 Wiley-Liss, Inc.

Future directions in sarcoidosis research: summary of an NHLBI working group.

Sarcoidosis is a systemic granulomatous disease of unknown etiology that primarily affects the lungs. The etiology remains unclear; however, environmental, genetic, ethnic, and familial factors probably modify expression of the disease. As an example, African Americans are at greater risk of mortality and morbidity than are white Americans, and more often have a family history of sarcoidosis. Most patients with sarcoidosis recover spontaneously, but some develop chronic, debilitating disease. Corticosteroids and other drugs, although effective at controlling disease activity, may not influence the overall course of disease. Because of the many uncertainties about the pathogenesis, course, and management of sarcoidosis, the National Heart, Lung, and Blood Institute convened a working group to identify future research directions and opportunities for sarcoidosis. These include developing a tissue bank, using novel methods to identify genetic factors, studying the immunopathogenesis with human tissue and animal models, exploring new approaches to diagnose and manage disease, and, finally, conducting randomized controlled trials to assess new therapies.

CARD15 gene mutations in sarcoidosis.

Sarcoidosis, Blau syndrome and Crohn's disease are complex disorders, characterised by granulomatous inflammation affecting a variety of organs. Mutations of the CARD15 gene, on chromosome 16, have been shown to contribute significantly to Crohn's disease and to cause Blau syndrome. These factors prompted the current authors to study CARD15 mutations in sarcoidosis. A total of 138 families were genotyped, including 302 patients with sarcoidosis and 127 patients without a family history of sarcoidosis (together with their parents), for four main coding CARD15 polymorphisms associated with increased risk of Crohn's disease. Furthermore, the gene segment that harbours Blau syndrome mutations was sequenced in 39 selected patients from 39 families with affected siblings identical for one or two parental chromosomes 16s and in eight patients from multi-case families. None of the reported Blau syndrome mutations and no new sequence alterations were found. There was an increased frequency of transmission of the rare allele of the polymorphic sites 802C>T (SNP5) and 2722G>C (SNP12) in at least one of the two study groups. In conclusion, CARD15 mutations, which are important in Crohn's disease and Blau syndrome, play no major role in sarcoidosis in this study population. However, these mutations could be of limited importance, especially in patients without a family history of sarcoidosis.

Radiotherapy for nasal congestion

Involvement of the larynx and nasopharynx in sarcoidosis is rare. Its course, like other forms of sarcoid, is one of remission and relapse usually responding to high-dose steroids or other forms of immunosuppression. We report a patient with nasopharyngeal and laryngeal sarcoid who failed to respond to immunosuppression but was treated effectively with low-dose radiotherapy. A 39-year-old Afro-Caribbean man presented in November, 1995, with reduced visual acuity. There was no medical or family history of sarcoidosis. Examination confirmed bilateral panuveitis. There were multiple cutaneous nodules on his limbs. Sarcoidosis was confirmed by skin biopsy, a raised serum angiotensin converting enzyme concentration of 109 IU/L, bilateral hilar lymphadenopathy on chest radiography, and characteristic lung function tests (FEV1 3·57 L, FVC 4·08 L, FEV1/FVC 88%, TLCO 4·8 mmol/min per kPa, predicted values FEV1 4·02 L, FVC 4·8 L, FEV1/FVC 84%, TLCO 11·13 mmol/min per kPa). His panuveitis responded to oral prednisolone 60 mg once daily and his lung function tests improved. Prednisolone was reduced to 20 mg once daily over 5 months with no relapse. However, 5 months after presentation, he developed nasal congestion and stridor. Indirect laryngoscopy revealed multiple nasopharyngeal and laryngeal nodules. A biopsy sample showed non-caseating granuloma consistent with sarcoidosis. Despite increasing prednisolone to 60 mg daily and adding cyclosporin, 400 mg once daily for 4 weeks, with satisfactory therapeutic blood concentrations, his nasal congestion and stridor progressively worsened. Cyclosporin was stopped, and on the basis of several successful reports of radiotherapy in steroid refractory neurosarcoid, we decided to treat him with low-dose external beam radiotherapy to his nasopharynx and larynx (20 Gys in 10 fractions over 2 weeks). He had complete remission of his symptoms at 7 weeks and they had not returned 12 months after radiotherapy. His present medication is prednisolone 15 mg once daily. This report is unusual in that sarcoidosis of the nasopharynx and larynx failed to respond to immunosuppressants but was successfully treated by irradiation. We do not advocate the routine use of radiotherapy for the treatment of this form of sarcoidosis on the basis of this single report, but suggest that it may be an alternative treatment in patients with life-threatening disease refractory to conventional immunosuppressant therapy.