An Interesting Case of Stridor With an Overlooked Clue

An Interesting Case of Stridor With an Overlooked Clue… May 18, 2004 -- Rheumatology Rounds Amir Ginzburg Case Presentation Identifying Data: • 58 year old woman, lives in a group home. Chief Complaint: • 5 day Hx wheezing and difficulty swallowing Past Medical History: • Schizophrenia - 10 year history • Seizure disorder x 4 years (2-3 sz per month) • Remote hysterectomy Case Presentation Medications: • Clonazepam 0.5 mg tid • Benztropine 2 mg bid • Perphenazine 8 mg bid • Carbamazepine 400mg bid Allergies: • NKDA Smoking: • Ex EtOH: • Prev. abuse Case Presentation History and Physical Exam: Dec. 2 • 2 weeks dysphagia, hoarseness. Also had weight loss x 6 months • Noted to have stridor, diffuse expiratory wheezes, excoriated rash over abd, back, arms, nape of neck, webspaces • Mild improvement with ventolin/atrovent • Dx: viral illness, scabies. Sent home. Case Presentation History and Physical Exam: Dec. 2 (cont’d…) • Bloodwork results reviewed after D/C home: 1.2 108 (MCV 77) 382 N 43 Ca, Mg, Phos, Albumin N ANC = 0.1 • Patient returned to ER at 19:30 (FORM 1) Case Presentation History and Physical Exam: Dec. 2 (cont’d…) • Reassessed. 94% on RA, afebrile. • Trachea midline, thyroid normal. • Stridor w/ each breath, decr. A/E to bases. • CVS, Abd normal. • CNS: – Crying/shouting, violent arm and leg movements requiring physical restraints. – Oriented to person only. No focal deficits noted. Case Presentation Course in hospital: Dec. 3 12:00 • ENT consult, given stridor, low sats with agitation • Indirect laryngoscopy: bilat adducted cords • Dx: bilateral vocal cord paralysis 17:00 • Increased agitation, 89% on 2L NP • Benztropine 2 mg STAT Case Presentation Course in hospital: Dec. 3 (cont’d…) 22:00 - Increased restlessness, 90% on 5L NP 22:45 - 85% on FiO2 0.4 FM 23:00 - 78% on FiO2 0.5 FM 23:30 - Increased stridor, 96% on FiO2 1.0 24:00 - Taken to OR for urgent tracheotomy. Post-op 100% on FiO2 0.35 Case Presentation Course in hospital: Dec. 4 • Started on G-CSF for neutropenia • 23:00- Temp 39.1 ºC (axilla), started empirically on Ancef / Tobra Dec. 6 • WBC 4.0, PMNs 2.6 on G-CSF • Antibiotics changed to Cipro / Clinda for presumed aspiration pneumonia Case Presentation Course in hospital: Dec. 7 • Seen by Hematology re: anemia and neutropenia. BM biopsy done. • BM Bx showed left shift with adequate granulopoiesis, otherwise normal • Dx not clear, ? anemia chronic disease Case Presentation Course in hospital: Dec. 23 • Patient pulled out tracheostomy tube • Found “blue, unresponsive” • Code Blue – Unable to re-insert tube – Small ETT inserted • Tracheostomy tube later re-inserted by ENT • Vocal cords “moving better” but still limited movement; cords “very edematous” Case Presentation Course in hospital: Dec. 31 • Noted to have ischemia of left hand D2-4, very tender, no necrotic areas • Seen urgently by Plastics cc3 who noted: – bilat ulnar deviat’n at MCPs w/ volar subluxed MC heads – MCP, PIP, DIP limited flexion w/ several Swan-necks – Pulp ischemia left hand D4 with small necrotic area; necrotic tip D2 • ? Ischemic changes 2º resp arrest Case Presentation Course in hospital: Jan. 10 • Referral to Rheumatology from Plastics. • Hand exam findings confirmed. • Multiple MTPs involved, with bilat knee effusions. • Positive Castell’s sign, ? palpable spleen tip. Case Presentation Summary Thus Far: • 58 F w/ seizure disorder and schizophrenia. • Presents w/ bilat vocal cord paralysis, neutropenia, anemia and 6 months wt loss. • MSK exam shows digital ischemia, swan necks, ulnar deviation at MCPs w/ volar subluxation, multiple active PIPs and MTPs, and knee effusions. • Also has ? enlarged spleen. • Can you guess the diagnosis? Case Presentation Investigations: • • • • • • • • • • • Rheumatoid factor > 656 (<11) ANA 1:320 homogeneous anti ds-DNA 148 (<150) anti Sm -ve anti RNP -ve anti Ro (SS-A) -ve anti La (SS-B) -ve anti Jo-1 -ve anti SCL 70 -ve LE prep positive (rare cells) Coomb’s negative • • • • • • • • • • • • C3 0.51 (0.75-2.1) C4 0.08 (0.12-0.55) IgG 22.8 (4.6-13.3), polyclonal IgA 3.98 (0.6-3.2) IgM 2.17 (0.2-2.2) Cryoglobulins -ve anticardiolipin -ve ESR 75 Haptoglobin 2.6 (0.38-1.9) Ferritin 342 (10-291) reticulocytes 66 TSH 3.49 Case Presentation Investigations: • Angiogram: – distal ulnar artery occluded just proximal to superficial arch, multiple digital segmental occlusions. – no aneurysms. – consistent with vasculitis. • U/S Abdomen – Spleen enlarged, “bulky”. Case Presentation Investigations: • Neck CT was ordered by ENT because of persistent vocal cord paralysis: – Inflammation of cricoarytenoid joints – ? Cricoarytenoid nodules So What’s the Diagnosis? SLE Features: • Seizures, chronic psychosis (schizophrenia) • Anemia (non-hemolytic), leukopenia • ANA, equivocal ds-DNA, LE cells, low C3/C4 RA Features: • Symmetric polyarthritis w/ hand involvement • EAMs: digital vessel vasculitis, nodules • High RF titre, anemia • Neutropenia, splenomegaly In the Time Remaining . . . • Diagnosis and treatment of Felty’s Syndrome • Prognosticators of RA disease severity • Cricoarytenoid involvement in RA • Rhupus Felty’s Syndrome • In 1924, Felty originally published a series of 5 patients with: (Johns Hopkins Hosp. Bull. 1924, 35:16) – Chronic arthritis – Splenomegally – Leukopenia (neutropenia) • True prevalence unknown, but likely 1-3% of RA patients (Ann Rheum Dis 1977, 36:500) Etiological Hypotheses • Closely related to LGL syndrome: – Non-erosive polyarthritis, splenomegaly, infections • 2 studies, total of 77 FS, 77 LGL (Arthritis Rheum 1997, 40:624-6; Rheumatology (Oxford) 2000, 39:393-8) – Very high prevalence of HLA-DRB1*0401 and HLA-DR4 in both FS and LGL • Both may represent parts of the same disease process NYD (Arthritis Rheum 1994, 37:1326-30) Clinical Features • 10 small case reports published prior to 1980 • No case series > 6 patients • FS occurred in patients with longstanding RF positive erosive / destructive joint disease • Higher prevalence of EAMs cf. RA • Nodules, vasculitis, Sjögren’s, neuropathy, pleuritis, episcleritis • Incr. incidence of NHL (Ann Int Med 1994, 120:35-39) Extra-Articular Manifestations RA (n=30) FS (n=24) Disease Duration Nodules Vasculitis Pulmonary Fibrosis Arthritis Rheum 1989, 32:1319-24 12 yrs 44% 7% 0% 20 yrs 62% 62% 29% • Vasculitis: – Leg ulcers, digital ischemia, nail fold infarcts – Large vessel vasculitis is rare Neutropenia • 10-20 in vitro studies of FS sera • Immune complexes phagocytosed by PMNs • Abnormal PMN function, reduced survival • Removed by RE system and/or sequestered • T- and B-cell mediated immunosuppression of granulopoiesis (Arthritis Rheum 2000, 43:834-43) • 60-95% of FS patients will have at least 1 infection; significant cause of mortality Serology RA (n=184) ANA Anti dsDNA* 38% 1% FS (n=110) 77% 27% ANCA Anti histone Anti Lactoferrin 36% 24% 4% 77% 83% 50% (Br J Rheumatology 1992, 31:185-8. Clin Exp Rheumatology 1993, 11:255-62. Arthritis Rheum 1989, 32:1319-24. : Medicine (Baltimore) 1990, 69:69-80) * Not well Studied. Small studies, +ve in 6-33% of patients Serology • High RF titre • LE cells have been reported (Arthritis Rheum 1989, 32:1319-24) • Low serum complement also reported • Cryoglobulins • Significance of these auto-antibodies in disease pathogenesis is not clear Recall the Serology in Our Patient • • • • • • • • • • • Rheumatoid factor > 656 (<11) ANA 1:320 homogeneous anti ds-DNA 148 (<150) anti Sm -ve anti RNP -ve anti Ro (SS-A) -ve anti La (SS-B) -ve anti Jo-1 -ve anti SCL 70 -ve LE prep positive (rare cells) Coomb’s negative • • • • • • • • • • • • C3 0.51 (0.75-2.1) C4 0.08 (0.12-0.55) IgG 22.8 (4.6-13.3), polyclonal IgA 3.98 (0.6-3.2) IgM 2.17 (0.2-2.2) Cryoglobulins -ve anticardiolipin -ve ESR 75 Haptoglobin 2.6 (0.38-1.9) Ferritin 342 (10-291) reticulocytes 66 TSH 3.49 Management G-CSF for Neutropenia: • 2 prospective studies, total of 12 patients (Semin Arthritis Rheum 1999, 29:82-99. QJM 1998, 91:49-56) • Raised PMNs to a level sufficient for joint replacement surgeries to be performed • S/E: may precipitate arthritis flare or vasculitis • S/Es minimized by using low doses Management DMARDS: • IM gold was previously 1st line therapy • Methotrexate is best (Br J Rheumatol 1998, 37:908-11) – 7 patients retrospectively followed – Sustained clinical improvement x 1 year – Decrease in active joints and normalization of granulocyte count Management Others: • Low dose glucocorticoids for short duration • Splenectomy – probably not effective • IVIG not effective • Testosterone – S/Es too toxic RA: Predictors of Severity Rheumatoid Factor: • EAMs (nodules, vasculitis) more common in seropositive RA and associated with incr. mortality (Ann Rheum Dis 1989, 48:7-13) • Good data: correlates with radiographic progression (OR ~12) and functional disability RA: Predictors of Severity CRP and ESR: • High correlation between cumulative CRP and radiographic progression, but usefulness limited by wide variations between patients (Br J Rheum 1993, 32(Supp 3):9-13) • ESR correlates as well: best data from 256 patients followed x 19 years (Arthritis Rheum 1998, 14:1571-82) • ESR + CRP better than either alone (Br J Rheum 1993, 29:111) RA: Predictors of Severity Anti-CCP (Cyclic Citrullinated Peptide): • OR 2.5 (95% CI 1.2-5.0) for radiographic progression x 5 yrs in 145 patients (Ann Rheum Dis 2003, 62:120-6) • May define subset of RF neg patients at risk of radiographic progression ( 178 RF neg patients followed x 2 yrs, PPV 40%, NPV 95%) (J Rheum 2003, 30:1691-5) • Anti-CCP + RF better than either alone (n=67): • RF predicted 58% of progressors, anti-CCP 54% • If both positive: 75% (Ann Rheum Dis 2003, 62:427-30) RA: Predictors of Severity Others: Ann Rheum Dis 2003, 62:427-30 RA: Predictors of Severity Others: • Anti-p68, Anti-RA33, Gal O glycoforms, CD40 ligand expression, anti alpha-enolase • Genetic factors: more progressive disease with certain HLA-DR4 alleles (Dw4/Dw14, Dw4/DR1) (Arthritis Rheum 1991, 34:822) Felty’s Syndrome? • More EAMs, very high RF titres • 88% of FS have Dw4 (Hum Immunol 1991, 32:56-64) Cricoarytenoids in RA • Studies since 1960 show cricoarytenoid arthritis in up to 26% of patients with RA • Case reports of cricoarytenoid involvement as sole clinical manifestation of RA • Laryngeal edema may lead to upper airway obstruction (stridor, dysphagia, hoarseness) • Tx can be emergent!! – airway control – glucocorticoids Cricoarytenoids in RA An interesting case report (March 2001): (J Rheumatology 2001, 28:624-626) A 56-year-old woman with RA suddenly developed severe respiratory distress and laryngeal stridor, which required endotracheal intubation. Laryngoscopy revealed cricoarytenoid arthritis. She was finally diagnosed as having overlap syndrome with RA and SLE. She was given high dose corticosteroids that improved her clinical symptoms and laryngoscopic findings. She represents the first patient with overlap syndrome who developed an acute airway obstruction due to cricoarytenoid arthritis. “Rhupus” • Panush, Edwards, Longley, Webster (Arch Intern Med 1988, 148:1633-6) • Prospective 11 year study • Of 7,000 new Rheumatology referrals, 6 patients identified • On average, 6.7 ARA criteria for RA and 4.2 criteria for SLE • Represents chance concurrence of RA + SLE So What Does This Patient Have? Is this Felty’s syndrome? Is this Rhupus? Is this Frhupus? Case Presentation Course in hospital: Jan 12 • Started on Prednisone 30 mg daily • Later started on MTX 15 mg weekly Mar 14 • Vocal cord paralysis much improved June 25 • Seizure free since prednisone and MTX Any Questions / Comments?