Rheumtacular! Mixed Connective Tissue Disease/Lupus Overlap?

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Thank you to Dr. Choi for this educational case of a young woman who presented with a diffuse presentation of concerning though nonspecific symptoms including subacute fatigue, malaise, and weight loss, with acute progressive hand swelling, foot swelling, bulky cervical lymphadenopathy, and multiple types of rash on her hands, legs, and upper trunk. She had multiple courses of antibiotics throughout this time which did not appear to improve nor worsen the symptoms. An extensive evaluation revealed diffuse lymphadenopathy, bilateral ground glass opacities and consolidations in a possible aspiration pattern, significantly elevated CK, high ANA titers at >1:2560, and positive anti-U1 RNP, anti-Smith, anti-Ro, and anti-LA antibodies with mildly reduced C3 and and reduced C4. While her presentation was considered nonspecific and not entirely compatible with any one syndrome, a provisional diagnosis of Mixed-Connective Tissue Disease with Systemic Lupus Erythematosis and Dermatomyositis overlap is considered. Ultimately she was started on high-dose steroids with calcium channel blockers and topical nitroglycerine for complicating Reynauds phenomenon.

  Courtesy Medscape

Courtesy Medscape

This case presented several clinical dilemmas, including timing and location of possible lymph node biopsy to rule out lymphoma given her diffuse lymphadenopathy and history of possible (though contested) MALT lymphoma on a previous periparotid lymph node biopsy. Ultimately the above serologies were not reassuring against the concomitant presence of lymphoma (as these can all be paraneoplastic syndromes, particularly DM), and an excisional lymph node biopsy was performed with preliminary read showing reactive node only.

Another interesting clinical decision point was whether to treat her mild hypoxemic respiratory failure and bilateral ground glass opacities as a possible aspiration pneumonia despite no compelling history of aspiration. Dr. Seaman prudently explored the possibility of esophageal dysmotility in the setting of possible CREST syndrome given her risk factors, and a barium swallow evaluation was normal. Treatment with antibiotics was favored once the risk/benefit ratio was deemed favorable, though a high index of suspicion for organizing pneumonia associated with her autoimmune disease burden is still being considered and followed.

This case highlighted the complexity of medical decision making that arises with nonspecific yet concerning syndromes. Our residents aptly homed in a representative problem statement focusing on which end organs appear to be involved in order to hone what could otherwise be an extremely wide-ranging and expensive evaluation into a more parsimonious approach that resulted in an early and appropriate decision to treat with immunosuppressants. The difficulty in elucidating this diagnosis and other undifferentiated connective tissue diseases is well-illustrated with this intimidating table from UpToDate:

  Courtesy UpToDate    [shutter]

Courtesy UpToDate

[shutter]

Mixed Connective Tissue Disease

Mixed Connective Tissue Disease is a syndrome with overlapping features of systemic sclerosis, systemic lupus erythematosus (SLE) and polymyositis and positive antibody against U1-RNP. (1) First desribed in 1972, it later became established as the first rheumatologic disease defined by a serologic test. Presenting symptoms can be diffuse, variable, and vague, and the diagnosis requires a high index of suspicion to achieve. While MCTD should be considered when patients presenting with features of lupus, dermatomyositis, polymyositis, or systemic sclerosis, the treatment of the disease is often guided by the predominant features of the presentation and overlaps signicantly with the treatment of the aforementioned syndromes. (2) Prognosis is variable though presence of anti-cardiolipin antibodies or presentations with features of dermatomyositis or polymyositis may portend a more severe disease course and worsened prognosis. (3)

Thank you again to Dr. Choi for this excellent learning opportunity.

References

  1. Sharp GC, Irvin WS, Tan EM, et al. Mixed connective tissue disease--an apparently distinct rheumatic disease syndrome associated with a specific antibody to an extractable nuclear antigen (ENA). Am J Med 1972; 52:148.
  2. Cappelli S, Bellando Randone S, Martinović D, et al. "To be or not to be," ten years after: evidence for mixed connective tissue disease as a distinct entity. Semin Arthritis Rheum 2012; 41:589.
  3. Gunnarsson R, Andreassen AK, Molberg Ø, et al. Prevalence of pulmonary hypertension in an unselected, mixed connective tissue disease cohort: results of a nationwide, Norwegian cross-sectional multicentre study and review of current literature. Rheumatology (Oxford) 2013; 52:1208.