Case presentation Chief complaint: A 39-year-old man presented with chest pain arthralgias for 2 months and drenching night sweats for 1 wk. HOPI: Chest pain: Middle & right chest pain for the past 2 months, radiating intermittently to right arm, increasing in intensity with deep inspiration or postural changes. Arthralgias: neck, shoulders, hips, knees, elbows, and wrists without swelling for the past several wks,. Drenching night sweats: 1 wk. Accompanied by fatigue & mild shortness of breath; no h/o associated wheezing, cough, or sputum.
PMH 1 yr ago: similar symptoms associated with diffuse arthralgias. EKG showed diffuse ST-seg elevations. CT chest: small pericardial effusion, thickened pericardium, several pericardial LN up to 0.4 cm & small L pleural effusion. PPD was negative Diagnosed as pericarditis, ibuprofen prescribed.
PMH 2 months ago: CT chest/abd/pelvis: pericardial thickening, which increased compared with the earlier study; the main pulmonary artery was distorted and narrowed to 2.6 cm(3.2 cm 1 yr earlier) at the level of the bifurcation; lymphadenopathy in the mediastinum, right hilar, and gastrohepatic regions was unchanged. There were no pleural or pericardial effusions, and there was no PE. Seen by cardiologist, cardiac stress test was negative. Arthralgias: seen by rheumatologist started on Prednisone (7.5 mg QD) for 2 wks.
PMH 4 yrs ago: H/o renal calculi 5 yrs ago: h/o vision loss R eye and periorbital headaches MRI: Enhancement of the frontal meninges and both optic nerves CT chest: R hilar lymph node(1 cm in diameter) Path of lung-biopsy showed no malignant tumor cells or granulomas. Diagnosed with optic neuritis and pseudotumor cerebri Prednisone [100 mg QD was continued for 3.5 yrs], acetazolamide, and oxcarbazepine were given.
Case presentation Allergies: penicillin. Social history: Ex-smoker, no alcohol or illicit drug use. Divorced, was sexually active, and worked as a machinist. Family history: Father died in MVA. Maternal GF CHF, maternal GM had a brain tumor, mother had fibromyalgia. Medications: prednisone(15 mg QD), ibuprofen [800 mg TID], and oxycodone– acetaminophen for pain.
Case presentation Vitals:B.P- 116/71, HR 74, RR 18, temp 36.3°C, Spo2 99% on RA. On exam: GEN: patient appeared tired. HEENT: The conjunctivae and oropharynx were injected. Visual acuity was impaired in the R eye. Neck: No JVD. No bruits. Nodes: soft LN(1-2 cm) in the axillae B/L S1 normal, S2 loud with a prominent split, and an ESM (grade 1-2/6) was loudest at the L upper sternal border. Ext: trace edema. MS: mild tenderness in the large muscle groups, with 4+/5 strength diffusely. There was full ROM in all joints and no swelling, redness, or effusions.
Labs CBC:WBC-15.4, Hb-12.5, Pl-600, N-71, MCV-79 BMP:WNL, LFTs: WNL, Cardiac enzymes: negative Serum PTH, 25-hydroxyvitamin D, and thyrotropin, were normal. ESR-53, IgA - 648 Tests for antibodies to ANA, ds DNA, anti-Smith, anti- RNP, anti-cyclic citrullinated peptide IgG, anti-La, and anti-Ro were negative. Hepatitis C and HIV, monospot test, RPR, Lymes serology and HBsAg were negative. PPD was negative Ferritin- 313, iron-19, SPEP- WNL, complements- WNL Blood and urine cultures were negative.
Investigations EKG: PR interval-256 msec and 1st degree AV block Echo: normal EF and MV, mild-to-moderate TR, mild RAE, mildly dilated RV. Homogeneous echodensities within the main pulmonary artery narrowed lumen to 1 cm; lumen of the right pulmonary artery was 0.8 cm at its origin. Flow velocities in the main pulmonary artery were increased, Velocities at level of pulmonary valve were normal. RVSP: 46 mm Hg. There was a small pl effusion and no evidence of pericardial constriction.
Transthoracic and Transesophageal Echocardiograms Merkel P et al. N Engl J Med 2008;359:1603-1614
Investigations MRI chest: mediastinum contained extensive soft tissue, surrounding the ascending thoracic aorta and portions of the R pulmonary artery, with 80% reduction in lumen of the proximal portion of the R pulmonary artery and moderate compression of the L pulmonary artery. Soft tissue enhanced after the administration of gadolinium.
Radiologic Images Merkel P et al. N Engl J Med 2008;359:1603-1614
Differential diagnosis Mediastinal mass: Tumors: lung, esophageal, vascular, thymic, or thyroid cancers Infections: TB, non-TB mycobacteria, actinimycosis and nocardiosis, histoplasmosis Systemic inflammatory diseases: Sarcoidosis, vasculitis Arthritis: Rheumatoid arthritis, SLE, Sarcoidosis, vasculitis, solid organ cancers like leukemia and lymphoma associated paraneoplastic arthritis, infections. Optic neuritis: TB, other infections[syphilis], sarcoidosis, vasculitis, lymphoma, SLE varaint lupus sclerosis
Hospital course During 1st 3 hospital days, night sweats occurred and Tmax was 38.1°C. Swelling of MCP & PIP joints of both hands developed, with tenderness on palpation and decreased ROM; swelling and limited ROM in both ankles and numbness over dorsum of the feet also developed. Day 4: MRI of the cervical, thoracic, and lumbar spine disclosed no abnormalities.
Diagnostic procedure Open biopsy of mediastinal surface, R ventricular masses and core biopsy of the R pulmonary artery Pathologic exam:granulomatous inflammation of surface and extensive necrosis in the deeper aspects of mass, small vessel neutrophilic vasculitis was noted.
Biopsy Specimens of the Mediastinal Mass (Hematoxylin and Eosin) Merkel P et al. N Engl J Med 2008;359:1603-1614
Hospital course IV methylprednisone 500 mg daily cyclophosphamide 300 mg daily Fever, arthritis and night sweats resolved and was d/c ed on tapering dose of steroids and cyclophosphamide Rpt echo 1 month later: resolution of abnormality of pulmonary artery. ANCA titres disappeared 1 yr later F-up imaging showed slight thickening of walls of aorta and main pulmonary artery, mediastinal mass is gone. 18 m later cyclophosphamide d/c ed & azathioprine 150 mg + prednisone 10 started
Final Diagnosis Wegener's granulomatosis involving the mediastinum, heart, and pulmonary artery.
Features of Wegener's Granulomatosis Merkel P et al. N Engl J Med 2008;359:1603-1614
Wegeners granulomatosis Definition: Clinicopathologic entity ch by granulomatous vasculitis of upper[95%] and lower respiratory tracts[85-90%] with GN. Variable degrees of disseminated vasculitis of small arteries and veins may occur. Prevalence: 3/100,000, rare in blacks M:F – 1:1, any age, 15%<19, mean age-40 Pathology: hallmarks-necrotizing vasculitis of small arteries and veins with granuloma formation-intravascular or extravascular. Increased incidence of venous thrombotic events.
Wegeners granulomatosis Organ system involvement: Lung involvement: typically multiple, b/l nodular cavitary infiltrates. Renal involvement: FSGN RPGN UR involvement: sinuses, nasopharynx-inflmn, necrosis, granuloma formation+/-vasculitis Eye: 52%-mild conjunctivitis, dacrocystitis, episcleritis, scleritis, retroorbital mass, granulomatous sclerouveitis, ciliary vessel vasculitis Skin lesions: 46% papules, vesicles, palpable purpura, ulcers, subcutaneous nodules-bx-vasculitis or granuloma. Cardiac: 8% pericarditis, coronary vasculitis, cardiomyopathy Nervous system: 23%- cranial neuritis, mononeuritis multiplex, cerebral vasculitis or granuloma Renal disease:77%- most of the mortality Non-specific symptoms- malaise, weakness, arthralgias, anorexia, weight loss
Treatment Cyclophosphamide induction for severe disease: 2mg/kg/day po with glucocorticoids [prednisone- 1mg/kg/day alternate day and then taper in 6m], monitor leukocyte count. Remission maintenance with azathioprine or methotrexate. Methotrexate induction for non severe disease. Biologic therapies: Etanercept-no sustained remission. Anti CD20[Rituximab]
Diagnosis Elevated ESR, mild anemia and leukocytosis, mild hypergammaglobulinemia[IgA], mildly elevated RA factor. 90% pts with active disease have a + antiproteinase-3 ANCA, inactive disease-60-70%