Felty’s Syndrome 8/13/2018

Narges presented a case of an elderly lady with chronic total body pain, found to have rheumatoid arthritis, pancytopenia, and splenomegaly… What could this be? Classic triad for Felty’s Syndrome!

We will start with a brief review of RA:

Rheumatoid Arthritis

  • Epidemiology
    • F : M = 3:1
    • Age of onset usually 50-75
    • Risk factors
      • Smoking
      • Nulliparity
      • Genetics (twins)
    • Extra-articular manifestation (40% cases will have some degree of involvement)
      • Bone: Osteoporosis, esp hip and L-spine
      • MSK: Myositis, muscle weakness
      • Vessels: Vasculitis
        • Neuropathy, pain (MSK vessel inflammation), skin ulceration
      • Skin: Rheumatoid nodule, skin ulcers esp LE, neutrophilic dermatoses
      • Eye: Episcleritis, scleritis, rare
      • Lung: Rheumatoid nodules, parenchymal disease, pleural disease, airway obstruction, pleural effusions (low glucose < 30)
      • Heart: Inc risk of CAD
      • Neuro: Inc risk for stroke
      • Kidney: Higher risk for development of rneal disease
      • Heme: Anemia, neutropenia, thrombocytopenia, inc risk of lymphoma
    • Diagnosis
      • Inflammatory arthritis 3 or more joints
      • RF or CCP
      • ESR/CRP elevation
      • > 6 weeks sx
    • Immunology
      • RF: Sensitivity 80%, Specificity 87%. 5-10% of healthy individuals might have positivity
      • CCP: Sensitivity 76%, Specificity 96%
    • Management (per American College of Rheumatology)
      • Treat ASAP, usually start with DMARD: Screen for latent TB, HBV and HCV prior!
      • HCQ (hydroxychloroquine): Baseline retinal screening and then annual after 5 years of use
      • SSZ (sulfasalazine)
      • MTX (methotrexate)
      • LEF (Leflunomide)
        • Mono
        • Double
        • Triple
        • Combo
      • Biologics
        • Tofacitinib (Janus kinase inhibitor)
        • Abatacept (T-lymphocyte inhibitor)
        • Tocilizumab (IL6 Ab)
        • Rituximab (CD20 MAB)
        • TNF: Etanercept, influximab
      • Steroids

RA Tx

Felty’s Syndrome

  • Epidemiology:
    • Occurs in ~ 1% of patients with RA
    • Not very well understood
    • Associated with HLA-DR4
  • Presentation: Triad of RA, pan-cytopenia, and splenomegaly
    • RA: Typically more severe, erosive, seropositive for RF +/- CP
      • More frequently with extra-articular manifestations
    • Neutropenia: Present in 100%, ANC < 2000 typically, usually with associated anemia + thrombocytopenia. Typically persistent
    • Splenomegaly: Present in most but does not correlate with disease severity
    • Inc risk for hematologic malignancy
  • Diagnosis
    • Clinical: Triad of RA, neutropenia, and splenomegaly
    • Immune: + DsDNA, anti-glucose 6 phosphate isomerase (92%), might have circulating immune complex formation (low complements)

If BM biopsy with lymphocyte infiltration = Large Granular Lymphocyte Syndrome (Pseudo-Felty’s), frequent infections, can progress to LGL Leukemia

Catastrophic Antiphospholipid Syndrome, +/- Heparin induced thrombocytopenia & thrombosis, +/- SLE 8/1/2018

Wendy presented a fascinating (and confusing!) case of a patient with history of APS and DVT/PE on chronic warfarin presenting with painful, non-blanching, palpable purpuric rash on the left thigh and lower abdomen found to have thrombocytopenia,  and proteinuria. Skin biopsy revealed small vessel microthrombi. Work up positive SRA, positive ANA, positive DsDNA, low complements… Base on this presentation, the patient possibly has catastrophic antiphospholipid syndrome, with heparin induced thrombocytopenia, and newly diagnosed SLE!

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Lupus nephritis – 7/26/18

Thanks to Naina for presenting an interesting case of a young woman presenting with fever, nausea/vomiting, and R flank pain found to have pyelonephritis and lupus nephritis!


Clinical Pearls

  • Renal involvement is noted in ~50% of patients with SLE and can present as nephrotic or nephritic syndromes.
  • The most common and severe form is diffuse proliferative lupus nephritis (class IV)
  • It is important to distinguish SLE flare from an infection. When infection is present, it must be treated first before starting immunosuppression.
    • SLE flare is associated with a normal WBC, low CRP (because CRP production by hepatocytes is down-regulated by type 1 IFN release in lupus flare), and absence of fever
  • Lab findings suggestive of flare include elevated anti-dsDNA (correlates with disease activity), low complement levels (predominantly C3 decline), worsening proteinuria, and elevated creatinine.

Capture

* Membranoproliferative GN can present with mixed nephrotic/nephritic picture.

SLE and renal disease:

  • Renal involvement is common and eventually occurs in ~50% of SLE patients
  • 10% progress to ESRD
  • High mortality compared to SLE w/o nephritis
  • More common and severe in African Americans, Hispanics, Asians and can be the only manifestation of lupus on presentation!
  • Classifications of GN:
    • Can evolve from one to another
    • Minimal mesangial lupus nephritis (class I)
      • Earliest and mildest form
      • Rarely diagnosed b/c pts have a normal U/A, no or minimal proteinuria, and normal Cr
    • Mesangial proliferative lupus nephritis (class II)
      • Microscopic hematuria and/or proteinuria
      • Light microscopy would show mesangial hypercellularity or mesangial matrix expansion
    • Focal lupus nephritis (class III)
      • Hematuria, proteinuria, some HTN, decreased GFR
      • Less than 50% glomeruli affected by light microscopy
      • Segmental glomerulonephritis
    • Diffuse lupus nephritis (class IV)
      • Most common and most severe
      • Hematuria, proteinuria, nephrotic syndrome, HTN, reduced GFR
      • Hypocomplementemia (esp C3) and elevated anti-dsDNA during active disease
      • >50% of glomeruli are affected
    • Lupus membranous nephropathy (class V)
      • nephrotic syndrome, Cr normal or slightly elevated
      • Diffuse thickening of the glomerular capillary wall and subepithelial deposits
      • Can present without any other clinical or serologic manifestations of SLE
    • Advanced sclerosing lupus nephritis (class VI)
      • Slow, progressive renal dysfunction with proteinuria and relatively bland urine sediment
      • Global sclerosis >90% of glomeruli
      • Active GN no longer observed
  • Treatment:
    • Best to initiate early but AFTER treatment of active infection:

      • Cyclophosphamide or Mycophenolate PLUS solumedrol 250-1 g/day x 3 days (former takes 10-14 days to have an effect so the latter is much faster) or prednisone 60 mg/day
      • Mycophenolate is the preferred choice to preserve fertility in women of reproductive age
    • Goals of therapy:
      • substantial reduction in urine protein excretion  to <0.33 g/day
      • improvement or stabilization of serum creatinine
      • improvement of urinary sediment

Dermatomyositis – Morning Report 4/24/18

Definitions

– Polymyositis = muscle weakness without cutaneous signs
– Dermatomyositis = muscle weakness and cutaneous signs
– Amyopathic DM = cutaneous signs without muscle weakness

Epidemiology

  • F:M = 2:1
  • Peak incidence is age 40-50 but any age affected

Clinical Manifestations

  • Muscle weakness in 90% of PM patients and 50-60% in DM – in DM, rashes usually come before or at the same time
  • Symmetric and proximal muscle weakness
  • If +distal muscle weakness, usually mild
  • Insidious onset usually for months before they go to doctors
  • Skin findings
    • Usually on the joints involved whereas lupus shows cutaneous things between the joints
    • Gottron’s papules and heliotrope rash
    • Facial erythema – includes nasolabial folds
    • Shawl and v-signs
    • Holster sign – lateral aspect of the thigh
    • Inflammation of the nail fold
  • Lung disease – 10% of cases of DM and PM
  • Malignancy – generally parallels that of the general population distribution
  • Esophageal disease – weakness of the muscles à dysphagia/regurgitation
  • Cardiac disease – conduction abnormalities and arrhythmias, increased risk of MI

Labs

  • Elevated muscle enzymes (CK, LDH, AST, ALT, aldolase)
  • ANA + in 80% of patients and myositis ab in 30-40% of patients (Jo, Mi2, SRP)
  • Elevated serum and urine myoglobin
  • ESR is normal or midly elevated

EMG

  • Normal in 10% of the patients