Asymmetric Polyarthritis in a Young Woman

Today's case was interesting and was predominantly related to diagnostic reasoning.  The patient is a young woman who presented with a year-long history of migratory arthritis with effervescent skin lesions in the area of the arthritis.   The affected joints were asymmetric, and currently involved the ankle and wrist.  She denied constitutional symptoms, alopecia, oral ulcers, photosensitivity, malar or discoid rash, hematuria, family history of connective tissue disease, or recurrent thrombosis/miscarriages.  There was no travel, and no recent infectious symptoms.   There were no other antecedent new medications, besides hydroxychloriquine having been started a short time prior to presentation.  There was no morning stiffness.

Her bloodwork revealed a microcytic anemia, leukocytosis, and normal platelet count.  Her creatinine was normal, but her urinalysis showed red cells and protein (microscopic to be performed).  Her ANA was positive at 1:320, and her anti-double stranded DNA was also positive at an outside lab (albeit not here).  Her c-ANCA was also positive.  The rest of the extractable nuclear antigens were negative.  The effused joints have not been sampled by arthrocentesis yet, and a skin biopsy is underway for the skin lesions which appear vasculitic.

There were multiple learning points from this case, and I want to stress that a seemingly complex case can be broken down into a group of syndromes such as “polyarthritis” in this case, and worked on from there:

-A polyarthritis involves a differential diagnosis which includes seropositive and seronegative entities. From the seropositive standpoint, the common things are systemic lupus erythematosus, rheumatoid arthritis, mixed connective tissue disease, and systemic sclerosis.

-There are several large groups of seronegative arthropathies, which are more likely to involve large joints in an asymmetric fashion.  These include inflammatory bowel disease-associated arthritides (usually flare concurrently with the IBD), ankylosing spondylitis, psoriatic arthritis, and reactive arthritis.  Finally, adult-onset Still’s disease would also be considered.  Typical findings would include fever, constitutional symptoms, lymphadenopathy, sore throat, a ‘salmon pink’ effervescent rash, an elevate ferritin, and leukocytosis.

-Psoriatic arthritis has five potential distributions of joint involvement: distal (DIP-predominant) arthritis, asymmetric oligoarthritis, symmetric polyarthritis (indistinguishable from rheumatoid arthritis), arthritis mutilans (destructive and deforming arthritis), and spondyloarthritis.  We discussed that the diagnostic/classification criteria for psoriatic arthritis do not mandate the presence of psoriatic skin plaques, and that they may only be discovered on a thorough skin examination after the incident presentation of the arthritis.

-We discussed reactive arthritis, which really encompasses three different syndromes.  The disease can occur following a dysenteric (bloody diarrheal) illness, following a genitourinary infection typically with Chlamydia or following a Group A streptococcal infection either through Acute Rheumatic Fever or an immune complex-mediated process.  Seeking these infectious syndromes is paramount in the diagnostic workup.

-We discussed a number of viruses that may cause joint symptoms.  While arthralgia (painful joints) are common in a number of viral infections (think of the last time you had a URTI!) only a few viruses can cause an arthritis (effused joints, or joints with pain on stress).  These include hepatitis viruses (particularly hepatitis B during immune complex clearance), acute HIV seroconversion illness, rubella, parvovirus B19 (associated with erythema infectiosum in children), mumps virus, dengue virus, enterovirus infections, and chikungunya virus.

-Other infectious etiologies included bacterial infections such as those occurring with infective endocarditis.  This can manifest either with multiple septic arthritis events as as embolic phenomena, or with an immune complex-mediated disease (remember that rheumatoid factor is often positive in bacterial endocarditis due to immune complexes).  Lyme disease could also be considered in this differential.  Both viral and bacterial causes are less likely to produce a year-long syndrome, making an inflammatory etiology more likely.

-Always consider systemic lupus in a woman of this age group.  The lupus classification crtieria include serositis (pericarditis/pleuritic), oral ulcers, photosensitivity, arthritis, blood abnormalities (cytopenias), renal disease (six types ranging from nephritic to nephrotic presentaitons), ANA, other immunological markers such as anti-Smith and anti-DS-DNA, neurologic disease, and the characteristic rashes.

Further reading:

Dhir, V., & Aggarwal, A. (2013). Psoriatic arthritis: a critical review. Clinical reviews in allergy & immunology, 44(2), 141-148.

Edwards, J., Paskins, Z., & Hassell, A. (2012). The approach to the patient presenting with multiple joint pain. Age, 15, 49.

Zochling, J., & Smith, E. U. (2010). Seronegative spondyloarthritis. Best Practice & Research Clinical Rheumatology, 24(6), 747-756.

Ytterberg, S. R. (1999). Viral arthritis. Current opinion in rheumatology, 11(4), 275-280.