Category Archives: Rheumatology

VA Ambulatory Report – Polyarthritis and Drug Induced Lupus

Case Summary: Thank you Alicia for presenting your clinic patient a 20 yo F with refractory epilepsy presenting with subacute migratory polyarthritis after starting Oxcarbazepine concerning for Drug-Induced Lupus on top of SLE.

 

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  • Patients with drug-resistant epilepsy should be seen at a specialized epilepsy center
  • Thanks Chris Sha for teaching us the top three causes of infectious polyarthritis: Disseminated Gonococcal disease, spirochetes, and viral (HIV, HBV)
  • Approach to arthritis: Consider basing it on number of joints and inflammatory vs. non-inflammatory
  • Differentiating drug-induced lupus from SLE is based on clinical picture and  laboratory findings.
  • Anti-TNF drugs are increasing in use and can cause an atypical presentation of drug induced lupus.

 

Drug-resistant epilepsy

  • No set definition, but has been proposed that drug-resistant epilepsy may be defined as failure of adequate trials of two antiseizure drug schedules (whether as monotherapies or in combination) to achieve sustained seizure freedom
  • Other forms of treatment may be considered; vagal nerve stimulation, surgery
  • If seizures are not controlled after 12 months, the patient should be referred to a specialized epilepsy center
  • Ambulatory EEG monitoring?
    • More cost effective than in-hospital EEG. Can increase the yield of detecting a seizure due to longer time on monitors and patient’s are less sleep deprived when sleeping in their normal environment.
    • Gold standard for differentiating non-epilieptic seizures from epileptic seizures is still in-patient EEG.

 

Flashback to Katie Auriemma’s post on an approach to polyarthritis from the Moffitt Pearls earlier this week.

Drug-induced lupus (DIL)

  • Common meds: procanamide, hydralazine, penicillamine, INH
    • Also seen with TNF-alpha inibitors
      • Can be more atypically presentation of DIL including negative anti-histone antibodies, hypocomplementemia positive dsDNA antibodies
  • More often causes superficial lupus symptoms (joint pain, rash) over visceral involvement (anemia, nephritis, serositis, etc)
  • Diagnosis
    • History of taking a known offending medication
    • Development of one feature of lupus
    • Serology: Positive ANA.
      • Positive anti-histone antibody is strongly suggestive.
        • Can be seen in idiopathic SLE but those patients will also have positive subserologies
      • You can also see a positive ANCA
    • Resolution of symptoms within weeks of stopping the offending agent

 

How do I differentiate between SLE and DIL? 

  SLE DIL
Clinical presentation Average age of onset 20 -30 y

More likely to affect African Americans than Caucasians

Female: Male 9:1

Average age of onset 50 -70 y

More likely to affect Caucasians than African Americans

Female: Male 1:1

Lab Findings ANA positive > 95%

Anti-histone antibodies in 50%

Anti-dsDNA in 80%

Low C3/ C4

 

ANA positive in > 95%

Anti-histone antibodies in > 95%

Anti-dsDNA can be present

Normal C3/C4

 

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VA Ambulatory Report 8.23.17 Polyarthritis

Thanks Hailyn for presenting this great case of a 40 yo female with a previous diagnosis of seronegative rheumatoid arthritis who presented to rheumatology clinic with new rash and ankle pain ultimately diagnosed with lupus.

Key learning points:

  • Use your physical exam: findings of synovitis can help narrow your differential to inflammatory causes of joint pain.  Nail changes such as pitting, splinter hemorrhages, and vascular irregularities are seen in several rheumatologic conditions.
  • About a quarter of patients with chikungunya will develop chronic polyarthritis
  • Drug induced lupus most often has superficial symptoms of skin and joint findings without visceral involvement.
  • ESR and CRP are indirect markers of inflammation but do not always directly correlate.  Lupus patients often have an elevated ESR and normal CRP due to the production of interferons that inhibit hepatocyte production of CRP.

 

What is the Seronegative rheumatoid arthritis?

  • Thanks Goop for pointing out the different terminologies used.   Some people use the phrase seronegative arthritis to describe a rheumatologic cause of arthritis that has not yet been determined.  Other names include arthritis NOS and palindromic arthritis.  Patients with these diagnoses may go on to develop a clear rheumatologic diagnosis such as rheumatoid arthritis or lupus.  Time (in addition to the appropriate serologies) is often a helpful diagnostic tool.

 

Characterizing joint pain: Think about the time course of symptoms, the number of joints involved, the asymmetry and size of involved joints, and if there is evidence of inflammation.

The rheumatology physical exam – synovitis and nail findings 

  • Synovitis
    • How do I assess for synovitis on physical exam?
      • Look for soft tissue swelling, warmth, joint effusion, and decreased range of motion
      • Joints with active synovitis feel boggy and cause lss ability to feel the bone prominences of the joint
    • Synovitis on physical exam suggests an inflammatory cause of joint pain and can help narrow your differential
  • Nail findings
    • Splinter hemorrhages: seen in endocarditis, scleroderma, psoriasis, RA
    • Pitting: Seen in psoriasis
    • Vascular changes
      • Get out that ophthalmoscope (or otoscope) and use some lubricant to magnify the vasculature bed of the nails
      • The vasculature of the nail bed normally is orderly and parallel
      • Patients with rheumatoid arthritis, SLE, dermatomyositis, or scleroderma the vasculature may be irregular, twisted, and dilated
    • Other resources for the physical of exam of the nails
      • The Standford 25:  http://stanfordmedicine25.stanford.edu/the25/hand.html#linseys
      • AAFP: http://www.aafp.org/afp/2004/0315/p1417.html

Chikungunya: In addition to the acute illness of fever, malaise, and polyarthralgia about 25-35% of patients develop a chronic inflammatory polyarthritis.

Drug induced lupus

  • Common meds: procanamide, hydralazine, penicillamine, INH
    • Also seen with TNF-alpha inibitors which are often used to treat RA and can cloud the clinical picture in a patient with an unknown rheumatologic disease such as this patient
  • More often causes superficial lupus symptoms (joint pain, rash) over visceral involvement (anemia, nephritis, serositis, etc)
  • Diagnosis
    • History of taking a known offending medication
    • Development of one feature of lupus
    • Serology: Positive ANA.  Positive anti-histone antibody is strongly suggestive. You can also see a positive ANCA
    • Resolution of symptoms within weeks of stopping the offending agent

 

What is the difference between ESR and CRP?

  • ESR
    • Measures the rate at which erythrocytes suspended in plasma settle in a test tube
    • An indirect measure of acute phase response due to increases in fibrinogen and immunoglobulins that then affect the sedimentation rate. However, many other things besides inflammation can affect the sedimentation rate.
    • Most often elevated due to inflammation (rheumatologic conditions, infections, malignancy, tissue injury) but there are several non-inflammatory causes of elevated ESR including:
      • Age
      • Female sex
      • Anemia
      • Renal disease
      • Obesity
      • Paraproteinemia
    • Causes of decreased ESR
      • Abnormalities in erythrocyte morphology
      • Extreme leukocytosis
      • Heart failure
      • Hypofibrinogenemia
  • CRP
    • Produced by the liver in response to IL-6 and other cytokines
    • Rises and decreases more rapidly than ESR
    • CRP is also a sign of inflammation and when markedly elevated if often an indication of infection or systemic inflammatory diseases
    • Mild elevations in CRP can be a sign of low grade inflammation  due to conditions such as atherosclerosis, obesity, OSA, insulin resistance, HTN
  • Discrepencies between ESR and CRP
    • Consider time course, non-inflammatory causes of elevated ESR, and low grade inflammation causing elevated CRP
    • Elevated ESR with normal CRP
      • Lupus: Often causes more marked elevations in ESR than CRP
        • Izzy thanks for teaching us that patients with lupus produce type 1 interferons which inhibit hepatocytes production of CRP
        • An elevated CRP in a patient with lupus can strongly suggest a bacterial infection over a lupus flare. The exception is lupus serositis which can large rises in CRP
      • Paraproteinemia
  • Review article from BMJ on the usefulness of inflammatory markers in clinical practice: http://www.bmj.com/content/344/bmj.e454

 

Moffitt Pearls – Rheumatology Report – 8.21.2017 – Evan’s Syndrome and SLE

Thank you to Leah for presenting a very interesting case of a young man with history of lupus c/b APS and DVT presenting with thrombocytopenia+ hemolysis found to have Evan’s Syndrome (ITP + AIHA)!

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Key Pearls

  1. Although the term is falling out of favor Evan’s syndrome describes the combo of ITP & AIHA.
  2. For unclear reasons, lupus flares are often accompanied by a dissociation between ESR (high) and CRP (nl or minimal elevation). Other findings of flare (vs. infection) include drop in complement, recued leukocyte count and + RBC casts and/or proteinuria.
  3. Direct oral anticoagulants have not been studied nor are they recommended as anticoagulants in patients with lupus and known DVT. Treat with warfarin or LMWH only!

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More on Evan’s Syndrome

  • Combination of Coombs-positive warm AIHA and immune thrombocytopenia (ITP).
  • Antibodies that cause platelet destruction are unique from those that cause AIHA.
  • Differential Diagnosis:
    • Infectious (eg, HCV, HIV)
    • SLE
    • Lymphoproliferative disorders
    • Common Variable immunodeficiency
  • Treatment (similar to ITP, however azathioprine and cyclophosphamide are used)
    • First line therapy: Glucocorticoid @ 1-2 mg/kg +/- IVIG
    • Second line: Azathioprine or rituximab
    • Third line: Splenectomy
    • Under investigation: Eltrombopag –> a TPO receptor agonist stimulating platelet formation

American College of Rheumatology Classification of SLE

[Always verify all prior diagnoses of rheumatological conditions]

  • SLE Criteria > 3 of 11 ( Se & Sp > 95% and all DO NOT have to be at the same time)
    • Cutaneous Manifestations
      • Malar Rash
      • Photosensitivity
      • Discoid Rash
      • Oral ulcer
    • MSK
      • Nonerosive arthritis – oligioarticualr; symmetrical, migratory
    • Cardiopulmonary
      • Serositis – pleuritic or pericarditis
    • Renal
      • Proteinuria or cellular Casts – > 500 mg/dL on UA or 3+ on dip

 

    • Neurological
      • Seizures OR psychosis

 

    • Hematological
      • Hemolytic anemia or leukopenia, or lymphopenia or thrombocytopenia
    • Serologies
      • +ANA
      • +anti-dsDNA or antiphopholipid Abs

 

Review of Hemolytic Anemias based on Smear

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Moffitt Pearls 8.8.17 – Undifferentiated systemic Rheumatic Disease & ILD

Thank you, Saate, for getting us started this am with a young man reporting 10 days of cough with complete white out of the left side of his chest found to have a large empyema!

Thank you, Emma and Gabby, for co-presenting the fascinating case of a young woman with history of RA coming in with persistent cough and fever.

**Key Pearls**

Ditty Pearl: Copper deficiency is an uncommon nutritional deficiency seen in patients after gastric bypass and results in a myelopathy localizing to the posterior columns and bilateral corticospinal tracts

Image Pearl: Tracheal deviation towards or away from a dense hemithorax can help distinguish volume loss (atelectasis) from a fluid occupying processes (i.e. lung collapse from massive pleural effusion or hemothorax)

Case Pearl: Rheumatologic diseases most frequently associated with pulmonary involvement, specifically ILD are scleroderma, myositis, dermatomyositis, MCTD and rheumatoid arthritis

Undifferentiated systemic Rheumatic Disease and Overlap Syndromes

  • As many as 25% of rheum disease in patients with systemic symptoms cannot be definitely diagnosed (don’t feel bad Emma and Gabby!)
  • Evaluation of a patient w/ possible autoimmune disease includes the following:

1) How was their disease diagnosed (clinical history and serologies)?

2) What therapies or diagnostic evaluations have they had?

3) What Rheum disease processes fall within their clinical presentation? (Use clinical history to dictate further work-up & serology evaluation)

ILD

 

VA Intern Report Pearls 6.8.17: Behcet’s and the Silk Road

Case summary

Thanks to Colin Purmal for presenting the case of a 26F presenting with diffuse abdominal pain, bloody diarrhea and oral ulcers, who was diagnosed with Behcet’s disease.


Top pearls

1. Oral ulcers have a fascinating differential, including infection, autoimmune disease, malignancy, medication-induced, and vitamin deficiencies. But the most common cause is the aphthous ulcer!

2. Consider treating severe infectious bloody diarrhea (e.g. systemically ill, immunocompromised or elderly) with ciprofloxacin. The benefits outweigh the risks except in cases with high concern for EHEC or Salmonella typhi.

3. Behcet’s disease is a key “Crohn’s disease mimicker.”


Oral ulcers

  • Pocket reference Ddx:

Infection– primary HSV, HIV,TB, CMV, EBV, coxsackie, GC/CT, syphilis, fungal

Autoimmune– Behcet’s, SLE, Crohn’s, blistering skin disease (Pemphigus)

Malignant– SCC, lymphoma

Aphthous

Meds- DIHS, SJS

Vit Deficiencies


Antibiotics in infectious bloody diarrhea

  • Most acute infectious diarrhea does not require antibiotic therapy.
  • 2001 IDSA guidelines for dysentery (to use the Oregon Trail-approved terminology) recommend obtaining stool cultures and treating empirically for 3 days in 3 cases: 1) toxic-appearing, 2) elderly, 3) immunocompromise.
  • The main benefit of antibiotic therapy is reduced duration of symptoms.
  • Ciprofloxacin is first-line, but Azithromycin can be used in pregnancy or if high suspicion for resistant Campylobacter (e.g. recent SE Asia travel).
  • Contraindications: 1) high concern for enterohemorrhagic E. coli (concern for precipitating HUS), 2) high concern for Salmonella typhi (concern for promoting carrier state and relapse)

IDSA Guidelines: http://www.uphs.upenn.edu/bugdrug/antibiotic_manual/idsadiarrhea.pdf


Crohn’s disease mimickers

  • Thinking about Crohn’s disease?
  • Consider Behcet’s disease in…patients from eastern Asia or the Middle East (the Silk Road!) with oral ulcerations (more frequent and more severe); genital ulcerations (more specific but less sensitive); systemic symptoms, including ocular symptoms, rashes, pan-vasculitis, weird clots (Budd-Chiari or cerebral venous thrombosis), pathergy (a 20G needle prick causes a papule or pustule within 48 hours).
  • International Study Group for Behcet’s Disease Diagnostic Criteria:
Recurrent oral ulceration: Aphthous (idiopathic) ulceration, observed by physician or patient, with at least three episodes in any 12-month period
Plus any 2 of the following:  
Recurrent genital ulceration Aphthous ulceration or scarring, observed by physician or patient
Eye lesions Anterior or posterior uveitis cells in vitreous in slit-lamp examination; or retinal vasculitis documented by ophthalmologist
Skin lesions Erythema nodosum-like lesions observed by physician or patient; papulopustular skin lesions or pseudofolliculitis with characteristic acnelform nodules observed by physician
Pathergy test Interpreted at 24 to 48 hours by physician

Behcet’s review: https://www.nature.com/nrrheum/journal/v9/n2/abs/nrrheum.2012.156.html

Moffitt Pearls 6.5.17 – Palpable Purpura

Thank you to Kenny for presenting a fascinating case of an elderly woman with a remote history of breast cancer presenting with SOB and weight loss found to have lower extremity edema, a diastolic murmur and finally skin findings that included palpable purpura and splinter hemorrhages!!!

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Key Learning Points

  • Diastolic murmurs are graded from 1-4 (thank you Arvind!)
  • Photos such as those presented in report can be uploaded via the Haiku app
  • Here is diagnostic pathway for palpable purpura Palpable Purpura

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As we discussed palpable purpura has an exhaustive list of etiologies – think big categories – Malignancy, Infectious and noninfectious endocarditis and primary rheum. In this patient in particular we had a discussion around sub-acute bacterial endocarditis given her diastolic murmur, splinter hemorrhages and palpable purpura.

Palpable Purpura

  •  A sign of vascular inflammation or damage, usually a small or medium vessel vasculitis
  • Palpable purpura is the hallmark of a leukocytoclastic vasculitis, but LCV is a histopathologic diagnosis

Ddx:

  •  Primary rheum
    • ANCA-associated
    •  Cryoglobuinemic vasculitis
    • Polyarteritis nodosa
    • Henoch-schonlein purpura (rare in adults)
    •      Urticarial vasculitiS
    •  SLE
  •   Infection
    •          HBV-associated PAN
    •          HCV associated cryoglobulinemia
    •          Purpura fulminans associated with DIC
  •   Malignancy-related
  •   Medication effect (meds can cause an LCV on their own!)

Recommendation for first line w/u of palpable purpura

  •          CBC w platelets
  •          ESR/CRP
  •          ANA
  •          ANCAs
  •          Complements
  •          UA
  •          Infectious w/u including Blood Cx, HIV, HCV, HBV, +/- ASo or strep throat culture and cryos

ZSFG Morning Report: Dactylitis ddx, IGRA’s, and a hint of NTM/TB

Thanks to Lily Kornbluth for presenting the case of a woman from China admitted with a swollen and painful finger which turned out to be mycobacterial dactylitis!

You’re probably asking yourself: Wait, aren’t those swollen digits just in psoriatic arthritis??? Do I have a framework or a DDX FOR DACTYLITIS??? Well, NOW YOU DO! Here’s a short list generated in report today with the help of Lisa Winston, Stephanie Cohen, Lily, and the #fabulous ZSFG resident crew!

dactyl 1

Dactylitis DDX:

Infectious:

  • NTM
  • TB
  • Syphilis
  • Leprosy
  • Fungi like Blasto, Cocci, Aspergillus
  • Bacterial tenosynovitis or septic arthritis or osteo w/ Staph, Strep, Gonorrhea, Nocardia, and Vibrio (this patient noted a history of food preparation…;)

Inflammatory:

  • Psoriatic arthritis
  • Reactive arthritis
  • Gout
  • Sarcoid
  • SLE
  • RA

Malignant: Leukemia

Heme: Sickle Cell dz

As we narrowed in on the dx, a diagnostic test returned: POSITIVE QUANTIFERON GOLD! Lisa Winston reminded us about the power of the QTF-Gold and that it’s more specific than the PPD! Here’s a quick refresher and an elegant representation of the box/test….
quant gold

QuantiFERON Gold or more technically since it just rolls off the tongue: Interferon-gamma release assays (IGRA’s):

  • What are they?
    • Diagnostic tools for latent TB indicating a cellular immune response to M. tuberculosis.
      • IGRAs can’t distinguish between latent and active TB aka don’t use them to dx active TB
      • IGRA’s available around the world: QuantiFERON-TB Gold In-Tube (QFT-GIT) assay, Quantiferon-TB Gold (QFT-G) assay, and the T-SPOT.TB assay

  • How do they work?
    • By capitalizing on the M. tuberculosis–specific antigens: early secreted antigenic target 6 (ESAT-6) and culture filtrate protein 10 (CFP-10)!
      • QFT-GIT assay is an ELISA-based test that uses peptides from three TB antigens (ESAT-6, CFP-10, and TB7.7). A positive test denotes IFN-gamma response to TB antigens that’s above the test cut-off.
      • Of note, ESAT-6 and CFP-10 are encoded by genes in the region of difference 1 (RD1) segment of the M. tuberculosis genome. These antigens are more specific for M. tuberculosis than the PPD because they are not shared with any BCG vaccine strains or most species of NTM.
        • HOWEVER: Two of the NTM that affect humans, Mycobacterium marinum and Mycobacterium kansasii, contain gene sequences that encode for ESAT-6 or CFP-10. So infxn with either of these NTM’s=positive QTF test 😦

  • What are their test characteristics?
    • IGRA’s have specificity >95% for diagnosis of latent TB, especially great as unaffected by BCG vaccination. The sensitivity for the IGRA’s T-SPOT.TB and QFT-GIT are 90 and 80%, respectively. PPD sensitivity as reference is 80%. Of note, IGRA sensitivity decreases in patients with HIV!

Once the deep skin biopsy came back “swimming in AFB’s,” we discussed how to approach mycobacteria based on rapid or slow growth. Here is a simplified algorithm to consider…
mycobact outline


Evernote: https://www.evernote.com/shard/s354/sh/5519f88f-3d0a-4769-8b82-a3a8017389f5/e810ad34c722821fe4f8b448bb7909e0

References:
*Lisa Winston, Stephanie Cohen, and ZSFG resident crew
*Pai M et al. Systematic review: T-cell-based assays for the diagnosis of latent tuberculosis infection: an update. Ann Intern Med. 2008 Aug 5;149(3):177-84. Epub 2008 Jun 30. PMID:18593687
*https://www.uptodate.com/contents/interferon-gamma-release-assays-for-diagnosis-of-latent-tuberculosis-infection?source=search_result&search=quantiferon&selectedTitle=1~96#H4850554