Common Rheumatologic Diseases

Common Rheumatologic Diseases

Rheumatoid Arthritis – Greg Jackson

Background

  • Proliferation of synovial tissue, mediated by TNF, IL-1, IL-6 leading to joint destruction
  • Chronic, inflammatory polyarthritis affecting the small joints of the hands, wrists, and feet
  • Pain and swelling of joints, typically symmetric MCP, wrists, MTP affected
  • Ulnar deviation, swan neck, boutonniere deformities are late manifestations of untreated disease
  • Morning stiffness lasting >1 hr suggests inflammatory arthritis like RA, but is not specific
  • C1-C2 instability: pts need evaluation with imaging prior to surgical procedure/intubation

 

Evaluation

  • Clinical diagnosis and positive RF, anti-CCP (as described in labs section above), though up to 30% patients have seronegative RA , elevated ESR and CRP
  • CBC, CMP, HIV, Hepatitis B and C screening; Quantiferon Gold (for possible biologics)
  • Obtain hand films to assess for osteopenia & erosions

 

Management

  • The majority of joint damage occurs early in the disease so early treatment paramount
  • DMARDs: start with MTX; if inadequate response, add biologic such as TNF inhibitors
    • Dosing: MTX 7.5-20 mg weekly; need to supplement with folic acid 1 mg daily
    • Requires routine lab monitoring for bone marrow suppression, lung and liver toxicity
    • Contraception must be used in women of childbearing age on MTX
  • Symptomatic/Flare treatment (no impact on disease progression):
    • NSAIDs: high doses required for anti-inflammatory effects (ie ibuprofen 3200 mg/day or 1000 mg/day naproxen), usually treat for 2 wks to achieve maximum analgesic effect
    • Prednisone 5-10 mg/day for 2 weeks and then slow wean off or low-dose (5 mg or less)

 

 

 

Anti-Phospholipid Syndrome – Gautam Babu

Background

  • Development of antiphospholipid antibodies (aPLs) = a heterogenous group of autoantibodies, which interact with endothelial cells through binding of β2GPI receptor
  • APLs induce a procoagulant and proinflammatory endothelial phenotype, resulting in arterial, venous, or small vessel thromboembolic events and/or pregnancy losses

 

Presentation

  • Common features: DVTs, thrombocytopenia, and livedo reticularis
  • Arterial thromboses: renal, mesenteric, coronary and cerebral vasculature 
  • Pulmonary embolism, CTEPH, nonbacterial vegetations (Libman-Sacks endocarditis)

 

Evaluation

  • Revised Sapporo classification criteria are used to diagnose patients with APS
  • At least one of the clinical criteria and one of the laboratory criteria are met:
    • Vascular thrombosis (arterial, small vessel, or venous)
    • Pregnancy morbidity
    • LA (lupus anticoagulant) present, on 2 or more occasions at least 12 weeks apart
    • aCL (anticardiolipin antibody) of IgG and/or IgM isotype in serum or plasma, present in medium or high titer, on two or more occasions, at least 12 weeks apart
    • Anti-beta-2 glycoprotein-I antibody of IgG and/or IgM isotype in serum or plasma, present on two or more occasions, at least 12 weeks apart
       

 

Management

  • Mainstay is anticoagulation for treatment and secondary prevention
  • Do not use (ASA or AC) for primary thrombosis prevention
  • Acute thromboembolism: Heparin gtt with bridge to warfarin
  • Secondary thrombosis prevention, anticoagulation with warfarin is preferred
    • Studies suggest that DOACs are less effective than warfarin
    • Goal INR 2-3 regardless of whether arterial or venous thromboembolism present
  • ASA 81 mg + warfarin for pts w/arterial events and risks for ASCVD

 

Systemic Lupus Erythematous – Greg Jackson

Presentation

  • Characterized by multisystem inflammation, precise etiology of disease unknown
  • Constitutional: fatigue, fevers, weight loss
  • Neurologic: cerebritis, myelitis, psychosis
  • Skin: malar rash, discoid rash, photosensitive rashes
  • Hematologic: leukopenia, anemia, thrombocytopenia
  • Pulmonary: pleuritis, pleural effusion, ILD
  • Cardiac: pericarditis/myocarditis (also due to underlying inflammatory condition have increased risk for coronary artery disease, similar to RA); Libman-Sacks endocarditis
  • Renal: nephritic/nephrotic syndrome
  • MSK: arthralgias/myalgias/arthritis

 

Evaluation

  • See section on rheumatology labs for specific sensitivity/specificity of tests
  • SLICC criteria not initially developed to diagnose SLE but often used:  need >/= 4/17 of SLICC criteria with >/=1 clinical and >/= 1 immunologic
     

Laboratory Criteria

Laboratory Criteria

Acute cutaneous rash (is Malar rash, etc.)

Elevated ANA

Chronic cutaneous Rash (i.e. Discoid rash, etc.)

Elevated anti-dsDNA

Alopecia, non-scarring

Positive Anti-Sm

Joint disease (Two or more joints with inflammatory characteristics)

Positive Anti-phospholipid Screen

Oral/nasal ulcers

Low C3/C4

Serositis (usually pleural or pericardial)

 

Neurologic (seizures, psychosis, AMS)

 

Anemia, leukopenia (<1000), thrombocytopenia (<100,000)

 

 

Management

  • Hydroxychloroquine mainstay of treatment, 200-400 mg/day, dose 5 mg/kg/day for long term to decrease risk of retinal toxicity
    • Monitor for retinal toxicity with yearly retinal exam
  • Glucocorticoids for flares (Similar dosing to RA)
    • Usually started with hydroxychloroquine and tapered once hydroxychloroquine has taken effect for symptom control
  • Other immunosuppressive medications (MTX, MMF, AZA, RTX) used with rheumatology consultation: MMF, cyclophosphamide used in SLE with renal involvement

 

 

 

 

 

Catastrophic Anti-phospholipid Syndrome (CAPS) – Gautam Babu

Background

  • Occurs in a small subset of patients with APS
  • Rapid development of thromboses in multiple small blood vessels in various organs resulting in multiorgan failure

 

Presentation

  • Similar presentation to APS, but multiple organs are involved in a short period of time
  • Renal (hypertension, proteinuria, hematuria, acute renal failure), Pulmonary (ARDS, PE), Central Nervous System (encephalopathy, stroke, cerebral venous thrombosis), Cardiac (coronary thrombosis), and Cutaneous (livedo reticularis, acrocyanosis, purpura, ecchymosis, splinter hemorrhages, and necrosis resulting in ulceration)
  • Pts can develop systemic inflammatory response syndrome 2/2 extensive tissue damage
     

Evaluation

  • Exclude other causes of small vessel occlusion: HIT, DIC or TMA
  • Definite diagnosis of CAPS is made when all four diagnostic criteria are present
  • Diagnosis is probable when a combination of these criteria is present
    • Evidence of involvement of three or more organs, systems, and/or tissues
    • Development of manifestations simultaneously or in less than a week
    • Confirmation by histopathology of small vessel occlusion in at least one organ or tissue
    • Laboratory confirmation of the presence of antiphospholipid antibodies:
  • Lupus anticoagulant, anticardiolipin antibodies, and/or anti-beta2-glycoprotein I

 

Management

  • Anticoagulation: Heparin gtt acutely
  • Transition to warfarin: If hemodynamically stable; no bleeding or recurrent thromboses
  • Immunosuppression: methylprednisolone 0.5 to 1 g intravenously daily for 3 days, subsequently followed by oral prednisone therapy at 1 mg/kg/day
  • Severe cases may require PLEX +/- IVIG
  • Refractory CAPS may require rituximab or eculizumab

 

 

 

Sarcoidosis – Jared Freitas

Background

  • Multisystem disordered defined by forming noncaseating granulomas in different tissues
  • Cardiac and neuro manifestations can be isolated

 

Presentation

  • Constitutional symptoms: fatigue, night sweats, weight loss, fevers, arthralgias, myalgias
  • Pulmonary symptoms (most common): dyspnea, cough, and wheezing
  • Extrapulmonary manifestations:
    • Cutaneous
      • Highly variable, but present in 25% of patients
      • Papules, macules, plaques that can be isolated or in groups, commonly involving neck, upper back, extremities; in African Americans can leave scars and depigmented areas
      • Lupus pernio: indurated, violaceous bumps on nose, lips, cheeks, ears
      • Erythema nodosum
  • Neuro
    • Affects 5-10% pts; involving any part of CNS or PNS, causing CN, hypothalamic, seizures, myelopathy or radiculopathy, hydrocephalus, aseptic meningitis
  • Cardiac
    • Granulomas can affect pericardium, myocardium and endocardium resulting in valvular disorders, conduction system and cardiomyopathy
  • Liver/Spleen
    • Granulomas in liver and spleen can lead to elevated LFTs, cirrhosis, anemia, leukopenia and thrombocytopenia (splenic sequestration)
  • Ocular
    • Photophobia, red eye, pain, blurry vision
    • Pts need eye exams to look for ocular involvement: uveitis (anterior and posterior), secondary glaucoma, retinal vasculitis, keratoconjunctivitis

 

Work Up

  • Requires combination of clinical presentation, radiographic manifestations, exclusion of other similarly presenting diseases, and noncaseating granulomas on pathology
  • CXR: hilar and mediastinal lymphadenopathy ± pulmonary infiltrates
  • High-Resolution Chest CT
    • Lymphadenopathy (bilateral and symmetric), with micro or macronodules, fibrotic changes (reticular opacities, traction bronchiectasis, volume loss)
  • PFTs
    • Typical findings: most sensitive is reduced DLCO, followed by reduced TLC, and then reduced VC (need to do full PFTs not just spirometry)
  • Labs:
    • CBC w/ diff, CMP, and urinalysis
    • ACE level is of limited clinical use
    • Testing for TB: Quant-Gold
  • Biopsy
    • Important to rule out mimics. The differential for “noncaseating granulomas” is extensive, including lymphoma and fungal infections
    • Not required for pts w/ asymptomatic bilateral hilar adenopathy or Lofgren syndrome (fever, erythema nodosum, arthralgias, and bilateral hilar LAD)
    • Target accessible lesions, like skin lesions or lymph nodes. May need bronchoscopy

 

Management

  • Most pts do not require therapy
    • Monitor symptoms, CXR, PFTs at 3-6 month intervals
  • Indications for treatment: progressive disease or severe disease at presentation
  • Mainstay of treatment is oral steroids:
    • Dosing usually 0.3-0.6 mg/kg daily for 4-6 weeks
    • If only symptoms is cough, could consider inhaled glucocorticoids
  • If unresponsive or unable to tolerate steroids may require alternative agents (MTX, AZA)