Category Archives: Rheumatology

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

 

 

 

MOFFITT MORNING REPORT PEARLS 5/24/17: Polyarthralgias and the Red Eye!

Hey Everyone! Thanks to Vaibhav for presenting the case of a young man with recurrent fevers, arthralgias, and eye inflammation (possibly iritis). The workup was pending but he had undergone an extensive infectious and inflammatory workup previously that was negative. We’ll have to wait and see if anything pops up this time. Pearls below on polyarthralgias and the red eye:

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Top Pearls:

  1. SLE joint symptoms usually manifest as a migratory, polyarticular, symmetric, non-erosive, inflammatory arthritis, though arthralgias without synovitis are not uncommon.
  2. When approaching polyarthralgia, look for the presence or absence of synovitis and the symptom duration as initial diagnostic branch points.
  3. Foreign body sensation localizes to the cornea, while photophobia could be corneal, anterior chamber/iris, or acute angle closure glaucoma.

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For those who want more info:

*Pearl: Arthritis/arthralgias in SLE– occurs in >90% and often one of the earliest manifestations. 65-70% of cases are true arthritis with inflammation, and tends to be migratory, polyarticular, symmetric, and non-erosive. However, occasionally erosive arthritis does occur in SLE.

See the algorithm below for an approach to polyarthralgia, and the table below for major causes of inflammatory polyarthritis.

*Take-home points are that the presence or absence of synovitis and the symptom duration are the most helpful initial diagnostic features.

 polyarthralgia

Inflammatory polyarthritis

The Red Eye: Classify by site of disease. The bolded ones require urgent/emergent ophtho referral!

  • Lids/lashes: hordeolum, chalazion, blepharitis
  • Conjunctiva: conjunctivitis (bacterial, viral, allergic), episcleritis/scleritis, hemorrhage
  • Cornea: abrasion, contact lens overwear, foreign body, infectious keratitis (bacterial, viral)
  • Anterior chamber/iris: iritis, hyphema, hypopyon
  • Lens: acute angle closure glaucoma

*Pearl: Foreign body sensation is fairly specific to corneal processes.

*Pearl: Photophobia could be corneal, anterior chamber/iris, or acute glaucoma.

Also see Rachel’s previous pearls on eye complaints in primary care:

https://ucsfmed.wordpress.com/2017/01/23/zsfg-report-pearls-eye-complaints-in-primary-care/

 

Evernote: https://www.evernote.com/shard/s272/sh/49bc2326-ca12-4739-b77f-4e3bb3c6acca/9d5d7ffa8039f7a873007e3e117b80f6

 

Have a great day everyone!

SamMy

MOFFITT CARDIOLOGY REPORT PEARLS 5/2/17: Kawasaki Disease and Coronary Aneurysms!

Hey Everyone! Thanks to Jin and Alayn for presenting the case of a young man with childhood Kawasaki disease coming in with progressive chest pain and dyspnea, and found to have a coronary aneurysm! He will undergo a cardiac stress test to figure out whether the symptoms are related to the aneurysm. Pearls below!

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Top Pearls:

  1. Kawasaki disease is usually self-limited, but cardiac complications are common.
  2. Coronary aneurysms are the most common complication.
  3. Treat early with IVIG and aspirin to prevent these complications.

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For those who want more info:

Kawasaki disease (KD) is rare in adults and is typically self-limited with an acute course of (average) 12 days. There DOES seem to be a genetic component to Kawasaki disease (increased frequency among family members of an index case and increased frequency in Asian and Asian-American patients).

*Cardiovascular complications include:

  • Coronary aneurysms (this is the major one, see below for more info!)
  • Heart failure
  • MI
  • Arrhythmias
  • PAD

*Diagnostic criteria: Fever lasting at least 5 days without other explanation, AND at least 4 of:

  • Bilateral conjunctivitis [>75%]
  • Oral mucous membrane changes (fissures, injection, strawberry tongue) [90%]
  • Cervical lymphadenopathy [25-70%]
  • Peripheral erythema or edema (palms/soles) [50-85%]
  • Polymorphous rash [70-90%]

*Treatment: IVIG (single dose), ASA during acute phase until inflammatory markers resolve. ASA is continued if aneurysms persist.

*Coronary artery aneurysms:

  • 30-40% of patients with acute Kawasaki disease!

 

  • 10-20% persist beyond one month (highest mortality is 15-45 days after disease onset)
  • May cause late ischemic heart disease
  • ECG and TTE for all patients with KD (CTA or MRA if TTE cannot image arteries)
  • Aneurysms most commonly found in proximal LAD, often at arterial branch points
  • “Giant” aneurysms >8 mm have high risk of morbidity/mortality (up to 50%), often anticoagulated in addition to aspirin
  • Who gets PCI? Ischemic symptoms + reversible ischemia on stress testing + >75% stenosis. CABG recommended if severe LV dysfunction or stenosis not amenable to PCI.

IN SUMMARY: If someone has suspected KD, treat early with IVIG and aspirin to prevent cardiac complications. Do ECG and TTE (and possibly CTA/MRA) in the acute phase looking for coronary aneurysms.

*Pearl: KD is not the only disease associated with coronary aneurysms. Other associations include PAN, Ehlers-Danlos, Loeys-Dietz, and other familial syndromes.

 

Evernote: https://www.evernote.com/shard/s272/sh/30ae8e3e-2d24-4074-b914-615906dac5ed/05ae900b26ab74cdec5d1c9a7d9a6bea

 

Have a great day everyone!

SamMy

MOFFITT AM REPORT PEARLS 4/7/17: Adult Still’s Disease!

Hey everyone! This morning we heard about a fascinating case of adult Still’s disease! Perhaps unsurprisingly at Moffitt, we have actually covered adult Still’s disease before…several times. Below are links to prior Blog posts about this topic, and some top pearls to take away.

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Top Pearls:

  1. Use the Yamaguchi criteria to diagnose adult Still’s disease.
  2. It is a diagnosis of exclusion!
  3. The four major criteria are fever, arthritis, rash, and leukocytosis.

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For those who want more info:

See these THREE prior Moffitt blog posts (lol)!

https://ucsfmed.wordpress.com/2016/12/22/moffitt-holiday-pearls-122216-mronj-and-adult-stills/

https://ucsfmed.wordpress.com/2016/04/12/belated-am-report-pearls-46-approach-to-joint-pain-stills-disease/

https://ucsfmed.wordpress.com/2015/11/10/moffitt-am-report-pearls-1110-approach-to-rashes-and-joint-painand-diagnosing-stills-disease/

  • The four major Yamaguchi criteria are:
  1. Fever of at least 39ºC (102.2ºF) lasting at least one week
  2. Arthralgias or arthritis lasting two weeks or longer
  3. A nonpruritic macular or maculopapular skin rash that is salmon-colored in appearance and usually found over the trunk or extremities during febrile episodes
  4. Leukocytosis (10,000/microL or greater), with at least 80 percent granulocytes

Treatment:

  • NSAIDs are good enough in 20% of patients and are 1st line for mild disease.
  • Glucocorticoids are 1st line for moderate to severe disease.

 

Evernote: https://www.evernote.com/shard/s272/sh/de612063-93cd-41ef-9f5c-1fd6acd03e7b/025c6adcd0f9fab451b3e8fd9ba82bbe

 

Have a great day everyone!

SamMy

MOFFITT RHEUMATOLOGY REPORT PEARLS 3/20/17: ANCA and Complement!

We had a terrific inaugural rheumatology report this morning with Sarah Goglin. Thanks to Max and Beth for presenting the case of an elderly woman with positive P-ANCA diagnosed with AIN on renal biopsy, likely NSAID-associated! Some highlights below:

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Top Pearls:

  1. ANCA positivity is not specific for vasculitis!
  2. When complement levels are low, there are immune complexes forming from somewhere!
  3. Complement levels are usually normal in ANCA-associated vasculitis (aka pauci-immune).

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For those who want more info:

See these prior Moffitt pearls on ANCA-associated vasculitides:

https://ucsfmed.wordpress.com/2016/04/08/am-renal-report-pearls-48-anca-vasculitides/

https://ucsfmed.wordpress.com/2015/11/13/moffitt-am-report-pearls-1113-rbc-casts-gu-tb-and-anca-associated-vasculitides/

Vasculitis isn’t the only cause of ANCA positivity! We expanded our differential for P-ANCA (MPO) positivity to include:

  • MPA
  • EGPA
  • Sometimes GPA! (usually C-ANCA but can be P-ANCA too)
  • SLE
  • RA
  • IBD
  • Malignancy
  • Chronic infection
  • Drugs (particularly PTU, sulfa, and hydralazine)
  • ILD (UIP and NSIP)! Thanks Sarah for sharing this recently described association.

See this recent article about ANCA and ILD: https://www.ncbi.nlm.nih.gov/pubmed/26994375

 

We also discussed our differential for low vs normal complement levels.

If C3 and C4 levels are low, the cause is immune complexes. Think SLE, Sjogren, MCTD, post-streptococcal GN, chronic infection (SBE, osteo), or cryoglobulinemic vasculitis (typically very low C4 level in this last one).

If C3 and C4 levels are normal and vasculitis is a concern, think ANCA-associated, drug-induced, malignancy, or IGA vasculitis (formerly HSP).

What about low C4 with normal C3? Think about disorders causing angioedema, either hereditary angioedema or acquired C1 inhibitor deficiency. Other causes include SLE, cryoglobulinemia, and membranoproliferative GN.

What about low C3 with normal C4? Uncommon in clinical medicine, indicates activation of alternative complement pathway. Occasionally happens in SLE, atypical HUS, contrast dye reactions, and transiently at onset of dialysis or ECMO. Most common in pediatric renal disease.

What about CH50? Measures total complement function and is more of a screening tool to detect a classical pathway deficiency. Here, we usually just send C3 and C4 and skip the CH50.

See these ZSFG pearls for a cool diagram at the end showing us how to think about small vessel vasculitis causes broken down by complement levels. Diagram copied below:

Vasculitis

https://ucsfmed.wordpress.com/2016/06/27/zsfg-pearls-627-leg-ulcer-ddx-cryoglobulinemias-compliment-levels/

 

Evernote: https://www.evernote.com/shard/s272/sh/630c4df9-5135-427a-9982-b21e6b56c0de/cee76b303367a5901114a993a748046b

 

Have a great day everyone!

SamMy