This is a story of a young woman in her 20s. She was otherwise healthy up until about a year ago when she developed ovarian torsion requiring oophorectomy which was uncomplicated. For the past month or so, however, she has been developing worsening joint pain and swelling, particularly in the hands, as well as dyspnea and chest pain. Her joints are associated with stiffness worse in the morning lasting an hour or sometimes all day. She also notes some generalized achiness and possibly some knee swelling as well. She also developed chest pain and shortness of breath around this time. The chest pain is achy, substernal/midline, worse with laying back and improved when leaning forward. She was initially dyspneic with exertion but now is short of breath at rest as well. In the last week, she also has developed nausea, vomiting, and diarrhea, and she has had one episode of hemoptysis. She was seen in the ER a couple times and dismissed with a “viral illness” given nonspecific symptoms. She has had no weight gain/loss, no leg swelling, no cough, no bleeding/bruising, no focal weakness, no rashes. Remainder of history is unremarkable, and she takes no medications.
Based on this initial presentation, what is your differential?
– This patient has multiple system involvement – CP/SOB, nausea/vomiting/diarrhea, hemoptysis, fevers, joint pain/swelling. Ideally we could come up with a unifying diagnosis but it may not be possible in this situation.
– CP/SOB: suggestive of pericarditis or possibly cardiomyopathy (consider valvular, ischemic, viral)
– N/V/D: very non-specific, limited history. Could be viral, which may go with cardiomyopathy
– Hemoptysis: also nonspecific. Consider bleeding diathesis, PE, drug use, malignancy, vasculitis
– Fever/Joints: infectious causes (septic joint), rheumatologic causes – SLE, vasculitis, reactive arthritis, RA
– It seems something rheumatologic or vasculitis would be the unifying system in this case
Her vitals on presentation were significant only for an oxygen saturation of 94% on 10L of O2! With conversation, she would desaturate to the 70-80s. She was otherwise obese but appeared overall better than she did on paper. OSH examination was documented as “normal” despite this finding. Later examination here noted diffuse crackles in the lungs as well as MCP and PIP joint swelling.
Labs were limited but significant for a Hgb of 6, Cr 2.17, ESR 95. Hemolysis labs negative. LFTs unremarkable except for albumin of 2. UA showed large blood/RBCs. ANA (+) and dsDNA (+) as well. Complement levels normal. p-ANCA and anti-MPO were (+). Anti-GBM (-). CXR demonstrated bilateral diffuse infitrates and CT chest showed a large pericardial effusion with alveolar infiltrates and air bronchograms, ultimately re-read by our radiologists as consistent with diffuse alveolar hemorrhage. TTE agreed with moderate pericardial effusion and LVH with normal LV function. Renal biopsy showed a pauci-immune pattern consistent with ANCA vasculitis.
Learning Points:
- SMALL vessel vasculitis that includes
- Granulomatosis with polyangiitis (GPA, formerly Wegener’s)
- Eosinophilic granulomatosis with polyangiitis (EGPA, formerly Churg-Strauss)
- Microscopic polyangiitis
- Drug-induced
- Other small vessel vasculitides include immune-complex (HSP, cryo, SLE, rheumatoid, Sjogren’s, Behcet’s, Goodpastures, and others)
- ANCA = anti-neutrophil cytoplasmic autoantibodies
- Discovered in 1982
- Seen on indirect immunofluorescence microscopy with two major staining patterns: cytoplasmic and perinuclear
- Also with two major antigens: anti-myeloperoxidase (anti-MPO) and anti-proteinase 3 (anti-PR3).
- Classically:
- C-ANCA = anti-PR3 = GPA
- P-ANCA = anti-MPO = EGPA, MPA
- Classically:
- GPA = necrotizing granulomas without asthma, often with sinus symptoms and glomerulonephritis
- EGPA = necrotizing granulomas with asthma, eosinophilia
- MPA = no granulomas, no asthma
- Often associated with “pulmonary-renal syndrome” = diffuse alveolar hemorrhage + glomerulonephritis2
- Bleeding into the alveolar space
- Most common causes:
- Vasculitides: ANCA-associated vasculitis; Goodpasture syndrome
- MCTD, SLE
- Coagulation disorders including APLA
- Symptoms/Signs
- Cough, hemoptysis, fever
- Acute respiratory distress
- Diffuse crackles, bronchial breath sounds, tachypnea may be noted
- Imaging4
- CXR is non-specific – diffuse or patchy opacification
- CT – diffuse, bilateral ground glass opacities that are more central than peripheral is classic
- Diagnosis
- Bronchoscopy
- PFTs – specifically, and increase in DLCO > 100%
- Not realistically feasible given (1) need proximity to the machines which do not typically live in the ICU and (2) has not been studied as to how to interpret these values with patient on oxygen
1 Jennette JC, Falk RJ. Small vessel vasculitis. N Engl J Med 1997;21:1512-23.
2 Brusselle GG. Pulmonary-Renal syndromes. Acta Clinica Belgica 2007;62:88-96.
3 Schwarz MI. The diffuse alveolar hemorrhage syndromes. King, TE, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com (Accessed on January 11, 2018.)
4 Thurston M, Weerakkody Y, et al. Diffuse alveolar hemorrhage. https://radiopaedia.org/articles/diffuse-alveolar-haemorrhage
