Case of a 63-year-old female with medical conditions of hypertension, chronic obstructive pulmonary disease, diabetes mellitus type 2, and pulmonary embolism (2013) presented to our clinics with progressively worsening purpuric lesions since 1 month prior to evaluation. She stated that these lesions began in the lower extremities and progressed to involve her buttocks, upper extremities, and ears. She denied any other systemic symptoms. Physical exam was remarkable for multiple, non-blanching, purpuric ecchymosis; many of them with central necrosis, associated erythematous borders, and retiform pattern. A biopsy of two of the lesions was performed which showed leukocytoclastic vasculitis with thrombosis of small vessels. Initial workup was unremarkable and included cryoglobulins, ANA, antiphospholipid syndrome antibodies, rheumatoid factor, anti-cyclic citrullinated peptides, anti-dsDNA, C-ANCA, P-ANCA, anti-Ro, anti-La, viral hepatitis panel, liver function tests, urinalysis, kidney function tests, urine and serum protein electrophoresis, antithrombin III deficiency, Protein C, Protein S, Factor V Leiden, PT, PTT, toxicology, and chest, abdominal and pelvic CT scan. The patient was admitted to internal medicine service for possible evaluation by rheumatology and hematology-oncology given progression of disease and unknown etiology. During hospital stay work up was repeated and found remarkable for positive cryoglobulins, strongly positive anti-citrullinated peptide, (>250 units) and positive rheumatoid factor levels. Patient was diagnosed with mixed type cryoglobulinemia secondary to preclinical RA. The patient was started on steroids with significant clearing of lesions and was later changed to azathioprine, which resulted in sustained remission.
Discussion: Retiform purpura involves a complete blockage of blood flow in the dermal and subcutaneous vasculature that results in purpuric lesions with a branched or angulated configuration. Determining the etiology of these lesions represents a major diagnostic challenge. In view of a skin biopsy showing leukocytoplastic vasculitis, positive cryoglobulins in serum, and clinical evidence of purpura, we can therefore conclude that our patient had a diagnosis of cryoglobulinemia. Her cryoglobulinemia was most likely of the mixed type given her negative workup for plasma cell dyscrasias. 10% of the cases of mixed cryoglobulinemia are idiopathic, meaning that the cause of such disease is unknown.
Although our patient did not meet the American College of Rheumatology rheumatoid arthritis (RA) criteria (<6 points), her strongly positive serology for RA correlates with an asymptomatic, autoimmunity phase known as preclinical RA, which has been described extensively in the medical literature. We came to the conclusion that our patient had mixed cryoglobulinemia secondary to preclinical RA, indirectly confirmed by her positive response to immunosuppression.
Conclusions: This case illustrates how characteristic skin lesions can encompass a wide variety of diagnosis requiring a systematic approach for diagnosis. In our case, skin biopsy showing small vessel involvement guided our diagnostic testing approach. Also, this case illustrates the importance of re-testing when a high clinical suspicion, based on history and physical examination, is present. Effective diagnostic testing is of great importance in order to avoid complicated laboratory evaluation, multiple specialist referrals, and delay of treatment.