A Case of IgG4-Related Disease with Bronchial Asthma and Chronic Rhinosinusitis in Korea
A 55-yr-old female with BA and CRS presented swelling of both eyes and neck aggravated 1 yr ago. The symptoms first developed 10 yr ago with cough, sputum, wheezing, nasal obstruction and rhinorrhea, which had remained with no change in size for 2 yr. She visited a local clinic due to the enlargement of a mass-like lesion 8 yr ago and then started to take 5 mg of prednisolone every other day. The swelling was temporarily reduced with a systemic steroid; however, the mass lesions were again aggravated whenever the steroid was stopped. She suffered from chronic cough with sputum and recurrent upper respiratory infections recent as of 1 yr; in addition, she was diagnosed with bronchial asthma 6 months ago. Her mass lesions were also aggravated in recent 1 yr; subsequently, she visited our hospital (October 2, 2012) for an evaluation of swelling of eyes and neck as well as recurrent respiratory infections. She experienced neither eye pain nor neck pain, did not complain of any visual problems or show systemic symptoms (such as febrile sensation and general weakness). Her asthmatic symptoms were well-controlled after being prescribed an inhaled corticosteroid. She had no previous history of any drug or food allergies. Her physical examination on the first visit revealed bilaterally swollen eyes and enlarged submandibular glands, with a size of 4×5 cm (). The diffuse swelling of both eyes was fairly well-demarcated, nodular and movable. There was no visual field defect or a limitation of ocular movement. The palpable masses of submandibular glands were movable and nodular without tenderness. Other organomegalies (except the lesions of eyes and neck) were not observed. The abdomen was not distended, there was no palpable lymph node, and her breath sound was clear without wheezing. Laboratory findings included a blood eosinophilia of 1,900/µL and elevated levels of erythrocyte sedimentation rate (ESR) 73 mm/hr, serum creatinine 1.6 mg/dL, and pancreatic enzymes (amylase 268 U/L, lipase 713 U/L). Total IgE level and eosinophil cationic protein (ECP) were also elevated (913 KU/L and >200 µg/L respectively). Serum lactate dehydrogenase (LDH, 113 U/L) level, liver function test and cardiac enzymes were within the normal range. Chest radiography and electrocardiogram showed no specific findings. To evaluate her asthmatic status, we performed a methacholine challenge test and the result was positive: provocative concentration causing a 20% fall in FEV1 (PC20), 0.86 mg/mL; FEV1/FVC, 64.57%; FEV1, 1.78 L; FEV1% predicted, 64.9%. A skin prick test (SPT) to all of the common inhalant allergens (Bencard, Bradford, UK) showed negative responses. We checked the serum levels of total IgG and IgG subclasses suspecting an IgG subclass deficiency due to an increased susceptibility to upper respiratory infection. The levels were markedly elevated: serum total IgG, 4,486 mg/dL (normal: 916-1,796 mg/dL); IgG1, 11,102.9 mg/L (normal: 3,824.0-9,286.0 mg/L); IgG2, 17,958.0 mg/L (normal: 2,418.0-7,003.0 mg/L); IgG4, 2,106.4 mg/L (normal: 39.2-864.0). Therefore, we suspected IgG4-RD on the basis of the mass lesions and elevated IgG4 level. Considering the possibility of systemic involvement of IgG4-RD, we performed multiple computed tomography (CT) scans of the neck, chest, and abdomen to establish the extent of the disease and to find any subclinical diseases. Neck CT imaging disclosed hypertrophies of extraocular muscles and the bilateral enlargements of lacrimal, submandibular and sublingual glands as well as mucoperiosteal thickening of maxillary and ethmoidal sinus indicating CRS (). Chest CT imaging study revealed that both lungs were diffusely involved with bilateral hilar lymph nodes, peribronchovascular bundle thickening, multifocal centrilobular opacities and interlobular septal thickening (). Irregular low density lesions of both kidneys and multifocal strictures as well as an irregular dilatation of the pancreatic duct were noted in the abdominal CT scan (). The right submandibular gland was biopsied to obtain a key pathological finding of IgG4-RD. The pathological features showed an abundant infiltration of IgG4-positive plasmacytes around the lymphoid follicles and glandular tissues. Cartwheel-like fibrosis (which is strongly indicative of IgG4-RD) was also noted (). Finally, we could confirm the diagnosis of IgG4-RD according to the criteria in 2011 (, ). We started a systemic steroid therapy with methylprednisolone 0.4 mg/kg/d. The nasal and asthmatic symptoms of the patient substantially improved and the elevated serum creatinine and pancreatic enzyme level was normalized at 2 weeks of follow-up. The masses significantly diminished with the treatment of a systemic steroid, which has been maintained with no recurrence. We performed follow-up measurements of lung function test 2 months later. Her FEV1% had improved to 103.8% predictive (2.82 L) compared to her initial FEV1 level (64.9% predictive, 1.78 L).