49-year-old Native American male, with a history of asymptomatic biopsy-proven sarcoidosis, presented to the Emergency department (ED) with progressive shortness of breath (SOB) and scant hemoptysis for 2 weeks. He also reports lower extremity pitting edema and constitutional symptoms of malaise and arthralgias. The patient reported that he has been taking 6 to 12 ibuprofen (non-steroidal anti-inflammatory drugs) a day for abdominal pain and that he had not been hydrating well. He denied pleuritic chest pain, fevers, chills, vomiting, diarrhea, constipation, new rashes, or skin changes. His past medical history also includes sickle cell trait, sarcoidosis, untreated marginal B-cell Lymphoma, and factor V Leiden deficiency. Family history is notable for a mother with systemic lupus and a father with large B-cell lymphoma.
Vitals were significant for new-onset hypertension in the 140s/90s, mild tachypnea (20-30 breaths/min), and oxygen saturation of 90%. Exam was consistent with bilateral crackles in lung and lower extremity pitting edema. Initial laboratory work up revealed acute kidney injury (AKI). Computed tomography (CT) showed bilateral ground glass opacities and bilateral moderate pleural effusions (Fig. 1). Echocardiogram showed no evidence of right or left heart dysfunction.
This presentation was inconsistent with a diagnosis of sarcoidosis as presence of pleural effusion is extremely rare in sarcoidosis. Therefore, the initial admitting diagnosis was bilateral pneumonia with NSAID-induced AKI. These two differentials seemed to cover many of his symptoms but left many unexplained, such as his new orthopnea, lower extremity edema, and hemoptysis.
Clinical status continued to deteriorate despite broad-spectrum antibiotics. The patient developed a painful, purpuric rash on the bilateral lower extremities, had ongoing hemoptysis and progressive sob. Bronchoscopy was done for evaluation of hemoptysis and was consistent with diffuse alveolar hemorrhage. His urinalysis showed4+ proteinuria and 1-2+ hematuria. Given AKI, proteinuria and hematuria, hemoptysis, and purpuric rash we broadened our differential to pulmonary renal syndromes/vasculitis including microscopic Polyangiitis (MPA), Granulomatosis with polyangiitis (GPA), Anti Glomerular basement membrane disease(anti-GBM), Systemic Lupus Erythematosus (SLE), and IgA nephropathy. C3 and C4 were low, all other serologies were negative including Anti Neutrophilic Cytoplasmic Antibody (ANCA), anti GBM, ANA and DsDNA.
In the absence of a clear diagnosis, a renal biopsy was performed which revealed Diffuse proliferative cryoglobulinemic (CG) glomerulonephritis type 1 (kappa restricted monoclonal deposition on Immunofixation). (Fig. 2).
Finally, the diagnosis of membranoproliferative glomerulonephritis secondary to type I cryoglobulinemia in the setting of marginal zone B-cell lymphoma was made.
White blood cell count 11.9 10*3/mul (normal 4000-9000) hemoglobin 11.4 g/dl (13.6-16.7), platelets 195 10*3/mul (130,000-350,000), sodium 134 meq/l (135-145), potassium 5.0 meq/l (3.4-5.2), blood urea nitrogen 51 mg/dl (7-22), creatinine 1.98 mg/dl (0.8-1.4), estimated glomerular filtration rate 36 ml/min/1.73m*2 (>60), albumin 3.4 gm/dl (3.5-5.2).
Urinalysis positive for 2+ urine protein, 2+ urine hemoglobin.
C3: 68.7 mg/dl (87-200)
C4: <8 mg/dl (19-52
Ana: Negative (<160)
DsDNA: Negative (<30 Iu/ml)
ANCA: negative (<20 titers)
anti GBM: 3 (0-20)
Hep B/C-Negative
Cryoglobulin: positive with cryocrit of 1%
Rheumatoid factor (RF): 19 (<14 Iu/ml)
Patient was emergently started on multimodal treatment including every other day plasmapheresis (total 27 sessions), high-dose dexamethasone, Cyclophosphamide, Rituximab and Vincristine. Patient also received hemodialysis sessions for his AKI.
Patient had prolonged hospital stay of over 2 months. Patient was subsequently discharged home with close follow up with multidisciplinary specialties including Rheumatology, Cardiology, Nephrology and Hematology/Oncology.
Unfortunately, our patient passed away at home seven weeks after final discharge due to unknown circumstances. Family refused autopsy.
1. CG is a challenging diagnosis. Clinicians need to keep differentials broad, despite evidence that may drift far from a textbook presentation of a diagnosis.
2. DAH is rare presentation in type 1 CG, when present can be life threatening.
3. Treatment of CG is focused on treating underlying disease.
4. Continuity of care is essential for the best patient outcome, as this rare disease portends a high rate of mortality.