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We read with interest the article by Kamisawa et al reporting IgG4 positive plasma cells in peripancreatic tissue, extrahepatic bile duct, gall bladder, and salivary gland (Gut 2003;52:683–7). The association of retroperitoneal fibrosis and sclerosing pancreatitis with IgG4 bearing plasma cells in the tissues of both lesions has been also reported.1
We would like to report the first case of interstitial pneumonia associated with autoimmune pancreatitis and IgG4 positive plasma cells in the intersitium.
Hyperamylasemia was detected in a routine blood examination in a 63 year old man who had been treated for duodenal ulcer at a clinic. He was admitted to our hospital for further examination. He did not complain of epigastralgia or back pain. Serum amylase was 323 (39–130 IU/l), IgG was elevated to 2350 (800~1600 mg/dl), and IgG4 was 1690 (<80 mg/dl). Antinuclear antibody, anti-SS-A antibody, anti-SS-B antibody, rheumatoid factor, and antismooth muscle antibody were all negative. Abdominal ultrasonography and computed tomography (CT) showed swelling of the head and tail of the pancreas. Endoscopic retrograde pancreatography showed irregular narrowing of the main pancreatic duct in the head and tail. Magnetic resonance cholangiography showed extrinsic stenosis of the lower common bile duct. The patient was diagnosed with autoimmune pancreatitis but he refused steroid therapy and was followed as an outpatient.
Three months later, honeycombing of the bilateral lower lung field was detected in a follow up abdominal CT. Chest CT revealed ground glass attenuation in the middle and lower lobe, and honeycombing predominantly at the back of the lower lobe, bilaterally (fig 1A). (Figure 1 (A–D) is available for viewing online at http://gut.bmjjournals.com.cgi/eletters/52/5/683#127.)
Retrospectively, a slight reticular shadow in the lower lung field was detected in the chest roentogenogram taken at the first admission but the lesion had progressed over three months. He was readmitted for further examination. He had a history of smoking 30–40 cigarettes a day for approximately 40 years. IgG was 3934 mg/dl, IgG4 was 2690 mg/dl, KL-6 was 1440 (<500 u/ml), serum amylase was 142, and lipase was 121 (0–49 IU/l). Schirmer’s test indicated a decrease in lacrimal secretion. Swelling of the head and tail of the pancreas were not changed on abdominal ultrasonography and CT.
With gallium scintigraphy, uptake was observed bilaterally at the back of the lower lobe, suggesting active pneumonia. Histology obtained by transbronchial lung biopsy from segment 8a of the right lobe showed marked thickening of the alveolar septum with marked infiltration of plasma cells and lymphocytes (fig 1B).
Immunostaining with IgG4 was performed using the immunoperoxidase method (mouse antihuman IgG4; ICN Biomedicals, Inc, Ohio, Canada). Infiltration of IgG4 positive plasma cells was detected in the alveolar septum (fig 1C).
Macrophages in the alveoli are considered to be due to smoking which often coexists with interstitial pneumonia in smokers.2
Because interstitial pneumonia associated with autoimmune pancreatitis was strongly suggested, prednisolone (40 mg/day) was administered for two weeks and then the dose was tapered. Chest CT taken two weeks after treatment showed that the ground glass attenuation in the middle and lower lobe had disappeared whereas the honeycombing remained (fig 1D).
Abdominal ultrasonography performed two weeks after treatment showed a marked decrease in the swelling the pancreas.
In the present case, infiltration of IgG4 positive plasma cells in the interstitium strongly suggests that the interstitial lung disease was associated with autoimmune pancreatitis. Interstitial pneumonia associated with Sjogren’s syndrome is unlikely in this case although there was decreased lacrimal secretion. Sicca syndrome observed in autoimmune pancreatitis is distinctive from classical Sjogren’s syndrome in that it is negative for anti-SS-A or anti-SS-B antibodies, serum IgG4 is elevated, and infiltration of IgG4 positive plasma cells in the salivary glands is observed.3
Autoimmune pancreatitis, in some cases, may be part of a systemic disease associated with IgG4.
We thank Dr Taniguchi et al for the interesting presentation of interstitial pneumonia associated with autoimmune pancreatitis (AIP).
We have experienced 24 cases of AIP but no cases showed interstitial pneumonia clinically. Recently, we immunohistochemically examined the organs of eight patients with AIP using anti-IgG4 antibody. IgG4 positive plasmacytic infiltration was detected in the portal area of the liver, gastric mucosa, colonic mucosa, and bone marrow as well as in the pancreas, peripancreatic tissue, extrahepatic bile duct, gall bladder, salivary gland, and lymph nodes of patients with AIP. However, few IgG4 positive plasma cells were observed in identical control specimens. From these findings, we proposed a new clinicopathological entity of IgG4 related autoimmune disease, and stressed that AIP is not simply pancreatitis but a pancreatic lesion involved in this systemic autoimmune disease.1,2 As IgG4 positive plasmacytic infiltration was observed in the transbronchially biopsied pulmonary specimens of the patient with AIP (unpublished data), it is likely that interstitial pneumonia occurs in association with AIP.