A 26-year-old woman presented with a six-year history of dry eyes and dry mouth, shortness of breath on exertion, and fatigue. She was in active military service at the time. Prior to the onset of shortness of breath, she had been in excellent physical health. Six years earlier, she had woken up with severe conjunctival injection attributed to a corneal abrasion. She was evaluated by an ophthalmologist and Schirmer's test was positive bilaterally. She received a presumptive diagnosis of primary Sjogren's syndrome confirmed by minor salivary gland and lip biopsy. She was treated with pilocarpine eyedrops for keratoconjunctivitis sicca. A year prior to visiting our center, she developed recurrent episodes of bronchitis complicated with pneumococcal pneumonia and sepsis. Since then, she had persistent shortness of breath. Two-dimensional echocardiogram did not show pulmonary hypertension. She had mild heartburn and an esophagram showed moderate esophageal dysmotility. No evidence of aspiration was found on a tailored barium swallow. She denied having Raynaud's phenomenon.
Pulmonary function tests demonstrated largely normal lung volumes with a TLC of 4.58 (95% predicted), reduced FEV1 of 2.39 L (77% predicted) and FVC of 2.89 L (80% predicted), and preserved FEV1/FVC ratio of 95% without significant bronchodilator response. DLco was reduced at 17.74 mL/min/mmHg (62% predicted). Serum protein electrophoresis and immunofixation did not demonstrate IgG kappa monoclonal protein.
Laboratory abnormalities included a very high titer ANA 1 : 5120 speckled pattern, elevated ENA profile at 121 units (normal value: <20 units), SSA/Ro 60 at 114 units, SSA/Ro 52 at 120 units (normal value: <20 units), SSB/La at 148 units (normal value: <20 units), and RF at 20 IUs/mL. Immunoglobulin A (IgA) and IgG were elevated at 1104 mg/dL (normal range: 50-462 mg/dL) and 3956 mg/dL (normal range: 700-1620 mg/dL), respectively, while IgM and IgG were within the normal limits. C4 was decreased at 18.3 mg/dL (normal range: 19-52 mg/dL). She had mild normocytic normochromic anemia, hemoglobin of 12.1 g/dL and hematocrit of 36%, with elevated inflammatory markers erythrocyte sedimentation rate at 69 mm/hr and CRP within normal limits.
An HRCT scan of the chest prior to our evaluation demonstrated pulmonary nodules, thin-walled cysts, basilar predominant ground glass attenuation, and subpleural consolidation (Figure 4(a)). Repeat HRCT demonstrated increased ground glass attenuation, bilateral solid pulmonary nodules, a few of which had slightly increased in size, and stable thin-walled cysts. The pattern was consistent with lymphocytic interstitial pneumonia (LIP) in the setting of Sjogren's syndrome (Figure 4(b)). Amyloidosis and lymphoproliferative disorder/lymphoma remained additional considerations for the solid nodules, which had increased in size.
The patient underwent CT-guided lung biopsy of the right lung upper lobe. This was unremarkable for malignancy; however, immunohistochemistry was consistent with light chain amyloid, while the kappa light chain staining was the strongest (Figure 5). There was significant lambda staining, but a clear monoclonal gammopathy was not identified. Amyloid staining did not confirm amyloidosis, and a Congo red stain was not detected.
The patient was initially treated with corticosteroid taper. She complained of symptoms consistent with neuropathy as well as constant vertiginous symptoms and visual disturbances of diplopia and intermittent pressure headache. Electromyography (EMG) and nerve conductive velocity (NCV) studies were within normal limits. She was found to have acetylcholine receptor antibodies.
The patient remained an active-duty soldier. We treated her for LIP with rituximab 1000 mg, 2 doses, 14 days apart every 6 months. Later, IVIG was added to her regimen to address nervous system involvement. Her exercise tolerance improved and DLco normalized (101% predicted).
In LIP, lymphocyte and plasma cells are diffusely infiltrated in the lung parenchyma, along with polyclonal plasma cells and lymphocytes. Elevated immunoglobulins IgA and IgG can be the results of polyclonal B cells. On three occasions, the patient's serum protein electrophoresis showed polyclonal gammopathy and on one occasion it showed monoclonal gammopathy. These gammopathies resolved with rituximab therapy, as did the level of immunoglobulins and RF and sedimentation rate. Follow-up HRCT showed an overall improvement in lung involvement characterized by a decrease in ground glass opacities and the solid component of nodules with stability of cysts. We could not exclude that the patient had a low-grade pulmonary lymphoma that responded to rituximab.