Granulomatosis In Patients Research Articles

Granulomatosis with polyangitis (WEGENER’S)- Strawberry gingivitis as prime manifestation

Wegener's granulomatosis (WG) is an immunologically mediated inflammatory disease. Major histological features include a necrotizing vasculitis involving small vessels, extensive “geographic” necrosis, and granulomatous inflammation. Clinical manifestations of WG are protean; virtually any organ can be involved. Further, the spectrum and severity of the disease is heterogeneous, ranging from indolent disease involving only one site to fulminant, multiorgan vasculitis leading to death. This case report documenrts the importance of considering Wegner’s granulomatosis in patients with unique gingival lesions. The most common presenttion is a friable-granular-hyperplastic gingivitis associated with alveolar resorption and tooth mobility. The disease may remain localized to the mouth for several weeks or months before multiorgan involvement occurs. Gingival enlargement is a direct manifestation of Wegener granulomatosis, and it may be pathognomonic. Failure to recognize the clinical lesions can result in delayed diagnosis and treatment, with potentially fatal results. Therefore, the aim of reporting this case was to emphasize that, the dental surgeon often being the first person to examine the oral cavity, should be familiar with the typical appearance of gingival WG as “strawberry gingivitis,” its clinical course as well as diagnostic parameters and adequate management. Keywords: Strawberry gingivitis, Wegener's granulomatosis, Antineutrophil cytoplasmic bodies, Geographic necrosis.

Exertional Dyspnea and New Onset Pulmonary Nodules in a 62-Year-Old Female With Seronegative Rheumatoid Arthritis

SESSION TITLE: Student/Resident Lung Pathology SESSION TYPE: Student/Resident Case Report Slide PRESENTED ON: Monday, October 30, 2017 at 03:15 PM - 04:15 PM INTRODUCTION: Tumor necrosis factor alpha (TNFα) inhibitors are important target therapies for inflammatory mediated diseases but they are not without adverse effects. CASE PRESENTATION: A 68 year-old Caucasian female with lichenoid dermatitis, psoriasis, rheumatoid variant psoriatic arthritis, COPD, and a former smoker was referred to Thoracic Medicine in 2016 for peripheral lung nodules (Fig 1) noted incidentally on a chest CT performed for a 3-month history of worsening dyspnea on exertion. In 2015 she had a negative quantiferon gold assay in preparation to start TNFα inhibitor therapy for recalcitrant psoriatic arthritis with which she struggled since 2013. After almost a year of increasing doses of methotrexate, it was discontinued for worsening gastrointestinal side effects. She further did not tolerate a 4-month course of sulfasalazine, 6-months of adalimumab, or a dose of infliximab. Finally, she was placed on golimumab- the newest TNFα inhibitor and in less than 6 months had near resolution of her arthritic symptoms. All serum calcium during this time was normal; there were no ACE levels available for review. Her exam was remarkable only for mild tenderness of the MCP joints and scattered deep-seated rose-colored papules coalescing into plaques over the hands. In office EKG was positive for new 1st degree heart block. Pulmonary function testing was consistent with restrictive lung disease and transthoracic echocardiogram was normal. An endoscopic bronchoscopy with biopsy of a right lung nodules was positive for non-caseating granulomas consistent with sarcoidosis (Fig 2). Golimumab was immediately discontinued and abatacept started. While her arthritic symptoms have started to worsen, her dyspnea has completely resolved. DISCUSSION: Sarcoidosis is a multisystem infiltrative granulomatous disease of unclear etiology. The paradoxical effect of TNFα inhibitors to both cause and treat sarcoidosis is not understood. The earliest reported occurence of sarcoidosis with a TNFα inhibitor is 6 months1-3. In this case, the newest TNFα inhibitor Golimumab, is not only associated with a new onset asymptomatic AV node block but also biopsy proven sarcoidosis with resolution of symptoms after the drug is discontinued. CONCLUSIONS: Clinicians should be aware of this rare but clinically significant association of Golimumab with pulmonary and possible cardiac sarcoidosis. Reference #1: Baughman RP, Drent M, & Kavuru M (2006) Infliximab therapy in patients with chronic sarcoidosis and pulmonary involvement. Am J Respir Crit Care Med. 174(7):795-802. Reference #2: Daïen, et al. (2009) Sarcoid-like granulomatosis in patients treated with tumor necrosis factor blockers: 10 cases.” Rheumatology 48(8):883-886. Reference #3: Harney S, Haroon M, & Ryan JG (2011) Development of sarcoidosis 6-month post discontinuation of etanercept: coincidence or real association? Clinical Rheumatology. 30(8):1095-1098. DISCLOSURE: The following authors have nothing to disclose: Kimberley Youkhana, Ibrahim Ismail-Sayed, Muhammad Younus, Sudheer Penupolu No Product/Research Disclosure Information

AB0452 Sarcoidosis: An underestimated and potentially dramatic side effect of anti-TNF-α

BackgroundA 41-year-old woman native from Senegal has a 22-year history of rheumatoid arthritis (RA). The past medical history was marked by a left upper tubercular pneumopathy. In the absence of...

New onset sarcoid‐like granulomatosis developing during anti‐TNF therapy: an under‐recognised complication

Tumour necrosis factor-alpha (TNF-a) antagonists have advanced the treatment of inflammatory arthropathies, and are even considered for use in refractory sarcoidosis with some success. Paradoxically, cases of new onset sarcoidosis-like diseases are increasingly reported in patients receiving TNF-a antagonists. Here, we report three cases of sarcoid-like granulomatosis that developed during treatment with TNF-a antagonists. Review of the Biologics clinic data base at Westmead, Sydney, Australia identified three patients whom, during anti-TNF therapy, developed non-caseating granulomas consistent with sarcoidosis. These three cases are described with review of the literature from 2000 to 2009 using PubMed. One hundred and sixty-nine patients within our data base were reviewed for the period 2003–2009. Sarcoidosis-like granulomas developed in three patients within a period of 3 to 36 months of treatment with etanercept and/or adalimumab. All cases demonstrated non-infective, non-caseating granulomas on renal or lymph node biopsy. Improvement was seen in two cases upon cessation of TNF-a antagonist and steroid therapy. Interestingly, clinical deterioration was noted upon re-challenge with the same TNF-a antagonist in one patient. To date, a total of 37 cases of sarcoid-like granuloma development after anti-TNF therapy have been reported in the literature. Development of sarcoidosis-like granulomatosis in patients treated with TNF-a antagonists is a phenomenon previously under-recognised. All three anti-TNF agents have been observed to cause this phenomenon, suggesting a ‘class effect’ rather than being drug specific.

Sarcoid-like granulomatosis in patients treated with anti-TNFα factors. A case report and review of the literature

This report describes a 56-year-old woman who developed granulomatous lesions consistent with sarcoidosis during adalimumab therapy for rheumatoid arthritis. Cervical and axillary lymphadenopathy developed approximately 21months after adalimumab administration. Non-caseating epithelioid cell granulomas consistent with sarcoidosis were detected both in an axillary lymph node specimen and in the bone marrow. Diseases showing similar histologic changes, especially tuberculosis, were excluded, and a diagnosis of sarcoidosis was made. Adalimumab was discontinued, and recovery was observed. The current case is, to our knowledge, the first to describe adalimumab-induced non-caseating granulomas in lymph nodes and bone marrow without pulmonary involvement in a patient treated for rheumatoid arthritis.

Comment on: Sarcoid-like granulomatosis in patients treated with tumour necrosis factor blockers: 10 cases: reply

Comment on: Sarcoid-like granulomatosis in patients treated with tumour necrosis factor blockers: 10 cases: reply

Comment on: Sarcoid-like granulomatosis in patients treated with tumour necrosis factor blockers: 10 cases

Comment on: Sarcoid-like granulomatosis in patients treated with tumour necrosis factor blockers: 10 cases

CLINICAL PICTURE OF PULMONARY LANGERHANS CELL GRANULOMATOSIS 2000–2008

PURPOSE: Pulmonary Lungerhans cell granulomatosis is a rare disease with variable clinical findings and uncertain prognosis. The aim of our study was to prospectively evaluate the clinical picture of pulmonary Langerhans cells granulomatosis in patients admitted to our Department in 2000–2008.

Sarcoid-like granulomatosis in patients treated with tumor necrosis factor blockers: 10 cases

TNF blockers have been recently evaluated for treating refractory sarcoidosis and could be efficient. However, several cases of sarcoidosis have been diagnosed during anti-TNF therapy. Here, we report the largest series of sarcoid-like granulomatosis following TNF blocker treatment. A call for observations of sarcoid-like granulomatosis following TNF blocker treatment was sent to the members of the French 'Club Rhumatismes et Inflammation'. Histological evidence of granulomatosis was required. Observations of 10 patients [seven females; median age 50.5 (range 27-72) years] with sarcoid-like granulomatosis while on anti-TNF treatment were collected: five were treated with etanercept and five with monoclonal antibodies; four patients received TNF blockers for RA and six for SpA. The median delay between anti-TNF agent introduction and granulomatosis diagnosis was 18 (range 1-51) months. Clinical symptoms were mainly pulmonary and cutaneous. Angiotensin-converting enzyme activity was increased in six cases. Lymph-node and/or lung involvement were observed by CT scan of the chest for eight patients. The median delay between drug discontinuation and remission was 6 (range 1-11) months for clinical signs and 6 (range 2-12) months for biological and radiographic findings. Improvement was observed in all patients after drug discontinuation with or without steroids. Sarcoid-like granulomatosis is rare but not exceptional in patients treated with TNF blockers (approximately 1/2800) and does not seem to be related to gender, rheumatic disease or in our series the type of anti-TNF drug used (monoclonal antibodies or soluble receptor). Discontinuation of anti-TNF usually leads to recovery.

Strawberry gums in Wegener's granulomatosis: a rare presentation

AbstractWegener's granulomatosis is a multisystem disease characterised by necrotising granulomatosis of the upper and lower respiratory tracts, disseminated vasculitis and glomerulonephritis. However, the clinical manifestations and organs involved in the disease vary widely. This case report documents the importance of considering Wegener's granulomatosis in patients with unique oral lesions. Failure to recognise clinical lesions can result in delayed diagnosis and treatment, with potentially fatal results.

Long-Term Follow-Up and Outcome of a Large Cohort of Patients with Common Variable Immunodeficiency

Common Variable Immunodeficiency belongs to the group of rare diseases encompassing antibody deficiency syndromes of highly variable clinical presentation and outcome. The multicenter prospective study on a cohort of 224 patients with Common Variable Immunodeficiency provides an updated view of the spectrum of illnesses which occurred at the clinical onset and over a long period of follow-up (mean time: 11 years) and information on the effects of long-term immunoglobulin treatment. The mean age at the time of diagnosis was 26.6 years. Seventy-five patients were younger than 14 years of age. The mean age at the onset of symptoms was 16.9 years. This implicates with a mean diagnostic delay of 8.9 years. Respiratory tract infections were the most prominent clinical problem observed at diagnosis and during the follow-up. Intravenous immunoglobulin administration induced a significant reduction in the incidence of acute infections, mainly acute pneumonia and acute otitis. However, a progressive increase in the prevalence of patients with chronic diseases, mainly sinusitis and lung disease, was observed in all age groups, including the pediatric population. The morbidity of Common Variable Immunodeficiency due to all associated clinical conditions increased over time despite an adequate replacement with intravenous immunoglobulins. Our data stressed the need to develop international guidelines for the prevention and therapy of chronic lung disease, chronic sinusitis, chronic diarrhoea, and chronic granulomatosis in patients with humoral immunodeficiencies.

A prospective study of antineutrophil cytoplasmic antibody (c-ANCA) and clinical criteria in diagnosing Wegener's granulomatosis

Summary Antineutrophil cytoplasmic antibody (c-ANCA) has a reported sensitivity and specificity greater than 90% for active Wegener's granulomatosis in selected patients with previously-defined disease. Because of these reports, some clinicians believe that a positive c-ANCA result provides strong circumstantial evidence for the diagnosis of Wegener's granulomatosis in patients with compatible clinical symptoms. However, this approach has not been examined prospectively. We prospectively studied 346 consecutive patients suspected of having vasculitis; those with previously established Wegener's granulomatosis (n=29) or receiving immunosuppressives other than corticosteroids (n=65) at baseline were excluded. Measures included a baseline c-ANCA, blinded chart reviews to record symptoms, physical findings, and corticosteroid use at baseline, and 2 to 8 months later to record final diagnoses and biopsy results. Wegener's granulomatosis was defined using the 1990 American College of Rheumatology (ACR) criteria, which does not require a biopsy. Follow-up information was available for 212 (84%) of the 252 patients eligible for this study (no corticosteroids: n=174; corticosteroids: n=78). 25 patients with compatible symptoms were classified with Wegener's granulomatosis by ACR criteria; only 6 of the 25 had biopsy-proven disease. 14 of these 212 patients had positive c-ANCA results. The overall sensitivity and specificity of c-ANCA for ACR-defined Wegener's granulomatosis were 28% (95% Cl, 10%-46%) and 96% (93%-99%) respectively. The positive and negative predictive values were 0·50 and 0·91. The specificity remained greater than 90% regardless of baseline corticosteroid use or disease activity; however, the sensitivity and positive predictive value remained poor. For Wegener's granulomatosis defined by biopsy criteria and compatible clinical symptoms, the sensitivity was 83% (53%-100%); however, the positive predictive value was 36%. These results raise serious questions about the use of positive c-ANCA tests in diagnosing Wegener's granulomatosis in patients with clinical symptoms alone.

Oral Presentation of Wegener Granulomatosis

Although the mouth is often involved in Wegener granulomatosis, oral lesions as the initial sign are rare. This case report documents the importance of considering Wegener granulomatosis in patients with unique oral lesions. The most common lesion is a friable-granular-hyperplastic gingivitis associated with alveolar resorption and tooth mobility. The disease may remain localized to the mouth for several weeks or months before multiorgan involvement occurs. Gingival enlargement is a direct manifestation of Wegener granulomatosis, and it may be pathognomonic. Failure to recognize the clinical lesions can result in delayed diagnosis and treatment, with potentially fatal results.

Lymphomatoid granulomatosis in the acquired immunodeficiency syndrome. Evidence of Epstein-Barr virus infection and B-cell clonal selection withoutmyc rearrangement

A case of lymphomatoid granulomatosis of lung that occurred in a patient with the acquired immunodeficiency syndrome (AIDS) was studied by light microscope, electron microscope, cell surface markers, and Southern blot test. Clonal selection of two clones of B-cells was seen. Two clones were infected with Epstein-Barr virus. There was no c-myc rearrangement. Lymphomatoid granulomatosis in patients with AIDS may represent multiclonal selection of B-lymphocytes in association with Epstein-Barr virus infection.