|Year : 2018 | Volume
| Issue : 1 | Page : 136-138
Unusual case of immunoglobulin G4-related disease
Prijesh Janardanan1, IK Biju2, Remesh Bhasi3
1 Department of General Medicine, Aster MIMS, Kozhikode, Kerala, India
2 Department of Gastroenterology, Aster MIMS, Kozhikode, Kerala, India
3 Department of Rheumatology, Aster MIMS, Kozhikode, Kerala, India
|Date of Web Publication||11-Jun-2018|
Dr. Prijesh Janardanan
Sreeji, Kalarikkal Paramba, Kovoor, Chevayoor PO, Kozhikode - 673 017, Kerala
Source of Support: None, Conflict of Interest: None
Immunoglobulin G4-related disease is a group of disorders, which was thought to be unrelated at first and now grouped together due to their common characteristics. This case is being reported for its unique presentation, rarity, difficulty in diagnosis, and recognition of the existence of the disease entity in this part of the world.
Keywords: IgG4-RD, Immunoglobulin G4-related disease, lymphadenopathy
|How to cite this article:|
Janardanan P, Biju I K, Bhasi R. Unusual case of immunoglobulin G4-related disease. Arch Med Health Sci 2018;6:136-8
| Introduction|| |
Immunoglobulin G4-related disease (IgG4-RD) is an increasingly recognized immune-mediated condition comprised of a collection of disorders that share specific pathologic, serologic, and clinical features. These disorders were previously thought to be unrelated.,, The commonly shared features include tumor-like swelling of involved organs, lymphoplasmacytic infiltrate enriched in IgG4-positive plasma cells, and variable degree of fibrosis that has a characteristic “storiform” pattern. In addition, elevated serum concentrations of IgG4 are found in 60%–70% of patients with IgG4-RD.
The majority of patients respond to glucocorticoids, particularly in early stages of disease.
| Case Report|| |
A 44-year-old female who is a homemaker presented with progressive abdominal distention, breathlessness, and edema of 2 weeks duration. She had no complaints of abdominal pain, and there was no alteration of bowel routine. She also did not notice any dark-colored stools. Breathlessness was not associated with cough or sputum production. Nor did she have chest pain, loss of appetite or loss of weight. She had pedal edema which was present throughout the day and was not associated with facial edema. She did not complain of orthopnea, paroxysmal nocturnal dyspnea, or palpitations. She did not have fever, body pain, or rashes. She had no history of jaundice in the past. There was no history of contact with a patient of tuberculosis or hepatitis. She also had no recent travel.
She was not a diabetic or hypertensive. Detailed family history taken did not reveal any similar illness in the family.
For the above complaints, she was evaluated in a nearby hospital. She was detected to have ascites, ascitic fluid study at that time was showing low serum-ascites albumin gradient (SAAG) and low adenosine deaminase (ADA), and cytology was negative for malignancy. Erythrocyte sedimentation rate (ESR) was persistently elevated upon repeated evaluation. Upper esophagoscopy was done in view of her complaints, which showed gastritis but showed no esophageal varices. Echocardiography was done which showed no abnormalities.
Hence, she was referred to our institution for further evaluation.
Routine investigations were rechecked, which showed elevated white blood cell count, reversal of albumin-globulin ratio, high ESR, alkaline phosphatase elevation, and elevated creatinine. An ultrasonogram was obtained to look for local causes, which showed splenomegaly with enlarged perihilar nodes and minimal ascites. Her hepatic vein and inferior vena cava were normal. Workup proceeded with an ascitic fluid study, which showed high SAAG and high protein with negative cytology for malignant cells and negative ADA. Her echocardiogram has been repeated to look for any evidence of constrictive pericarditis or right heart disease and was noncontributory. Chest X-ray was taken which showed bilateral pleural effusion. Serological markers for HIV and hepatitis B and hepatitis C viruses were negative. Paul–Bunnell test was also negative.
With adequate hydration, her creatinine came down to normal values and contrast-enhanced computerized tomogram (CT) of the thorax and abdomen was obtained which showed mild ascites with bilateral enlarged intra-abdominal nodes, splenomegaly, and mild pericardial and pleural effusion. Diagnostic laparoscopy was performed which showed multiple perisplenic nodes, but peritoneum and mesentery were normal. Biopsy from the perisplenic nodes showed reactive hyperplasia. Mantoux test done was negative.
At this point in time, our provisional diagnosis included connective tissue disorders, lymphoma, and disseminated tuberculosis.
While in hospital, she had developed new sign in the form of axillary lymphadenopathy. CT of the chest was done to look for further causes of dyspnea and to investigate the possibility of tuberculosis. CT of the chest revealed enlarged mediastinal, bilateral axillary, and intra-abdominal lymph nodes thought to be of inflammatory nature and mild pericardial and bilateral pleural effusion.
In the pretext of high ESR, reversal of albumin-globulin ratio, and multiple lymphadenopathy, both chronic infection and connective tissue disorder were considered likely.
Workup for connective tissue disorders was done, of which antinuclear antibody (ANA) was negative and ANA profile showed anti-Sjogren's syndrome-related antigen A positivity.
Axillary lymph node biopsy was done which showed follicular hyperplasia and increase in interfollicular plasma cells [Figure 1] and [Figure 2], which was indicative toward IgG4, related lymphadenopathy, or Castleman disease. Further, IgG4 staining was done, which showed immunomorphological features consistent with IgG4-related lymphadenopathy [Figure 3].
|Figure 3: Axillary lymph node biopsy immunoglobulin G4 stain (high power)|
Click here to view
She was started on intravenous (IV) methyl prednisolone after the biopsy report confirmed the disease.
She became better, her abdominal distension came down, and she was no longer breathless after 20 days of treatment. Edema subsided within the next few weeks. She had a stable course while in hospital after initiation of steroids. IV steroids were replaced by oral steroids, which were tapered subsequently to low-dose prednisone. Since she had signs of disease activity, azathioprine was also added. She is doing well with the combination of low-dose steroids and azathioprine and is free of any symptoms 1 year into follow-up.
| Discussion|| |
Lymphadenopathy is a common occurrence in IgG4-RD; it can appear before, concurrent with, or after the diagnosis of this disease. Although multiple lymph node groups are commonly involved, constitutional symptoms are absent. The lymph nodes can show a broad morphologic spectrum, including multicentric Castleman disease-like (Type I), follicular hyperplasia (Type II), interfollicular expansion (Type III), progressive transformation of germinal centers (Type IV), and inflammatory pseudotumor-like (Type V). All are characterized by an increase in IgG4+ plasma cells (>100 per high power field) and IgG4/IgG ratio (>40%).
Symptoms occasionally occur due to mass effect of the enlarging nodes; individual nodes are typically no >2 cm in diameter but may range up to 5 cm. Multiple groups of lymph nodes are usually involved; the mediastinal, hilar, intra-abdominal, and axillary are most common and can be readily seen upon scanning with gallium-67. The lymphadenopathy is generally nontender, and the nodes themselves are rubbery rather than hard.
The diagnosis of IgG4-RD requires characteristic findings upon biopsy of affected tissue, but additional organ involvement may be possible to identify through a careful history, physical examination, routine laboratory testing, and selected imaging studies. Tissue biopsy is one such confirmatory test especially in case where specific tissue involvement is identified. Lymphadenopathy is one such instance where the diagnosis can be made out from the tissue sample. The serum IgG4 level was elevated above the upper limit of normal (>135 mg/dL) in 86% of 114 patients in one study. The degree of IgG4 elevation correlates imperfectly with the degree of disease activity but is often a useful parameter to follow in individual patients. So far, there has not been consensus upon the diagnostic criteria of IgG4-RD. Postdiagnosis evaluation is necessary to know the extent of involvement of other organs so as to decide upon treatment strategies.
The optimal treatment for IgG4-RD has not been established. Most patients respond to glucocorticoids within several weeks, typically with symptomatic improvement, reductions in the size of masses or organ enlargement, improvement in organ function, and often a decrease in serum levels of IgG4. However, some require a few months to respond, and there are some patients who relapse and others who respond less well or not at all initially. The current recommendations advocate the use of prednisolone, rituximab, azathioprine, and also mycophenolate mofetil for the optimum control of symptoms in IgG4-RD.
We sincerely thank Dr. Shalini Kuruvilla, Senior Consultant, and Dr. Shehla Basheer K, Junior Resident, Department of Pathology, MIMS, Kozhikode, Kerala, India, for providing the histopathological slides.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Stone JH, Zen Y, Deshpande V. IgG4-related disease. N
Engl J Med 2012;366:539-51.
Kamisawa T, Funata N, Hayashi Y, Eishi Y, Koike M, Tsuruta K, et al.
Anew clinicopathological entity of IgG4-related autoimmune disease. J Gastroenterol 2003;38:982-4.
Khosroshahi A, Stone JH. A clinical overview of IgG4-related systemic disease. Curr Opin Rheumatol 2011;23:57-66.
Okazaki K, Uchida K, Koyabu M, Miyoshi H, Takaoka M. Recent advances in the concept and diagnosis of autoimmune pancreatitis and IgG4-related disease. J Gastroenterol 2011;46:277.
Cheuk W, Chan JK. Lymphadenopathy of IgG4-related disease: An underdiagnosed and overdiagnosed entity. Semin Diagn Pathol 2012;29:226-34.
Saegusa H, Momose M, Kawa S, Hamano H, Ochi Y, Takayama M, et al.
Hilar and pancreatic gallium-67 accumulation is characteristic feature of autoimmune pancreatitis. Pancreas 2003;27:20-5.
[Figure 1], [Figure 2], [Figure 3]