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|Ahead of print publication
Primary sjögren's presenting with glomerulonephritis, pure motor neuropathy, pancreatitis, and hypogammaglobulinemia
Kunal Chandwar1, Prasanna Dogga1, Juhi Dixit1, Kriti Kishor1, Rasmi Ranjan Sahoo2, Anupam Wakhlu2
1 Department of Clinical Immunology and Rheumatology, King George's Medical University, Lucknow, Uttar Pradesh, India
2 Department of Clinical Immunology and Rheumatology, King George's Medical University; Department of Clinical Immunology and Rheumatology, Apollomedics Superspeciality Hospitals, Lucknow, Uttar Pradesh, India
|Date of Submission||15-Dec-2021|
|Date of Acceptance||17-Mar-2022|
|Date of Web Publication||03-May-2022|
Department of Clinical Immunology and Rheumatology, Apollomedics Superspeciality Hospitals, Lucknow, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
|How to cite this URL:|
Chandwar K, Dogga P, Dixit J, Kishor K, Sahoo RR, Wakhlu A. Primary sjögren's presenting with glomerulonephritis, pure motor neuropathy, pancreatitis, and hypogammaglobulinemia. Indian J Rheumatol [Epub ahead of print] [cited 2022 Oct 1]. Available from: https://www.indianjrheumatol.com/preprintarticle.asp?id=344592
A 40-year-old female, with a 6-year history of inflammatory arthritis, recurrent oral ulceration, and anemia requiring multiple blood transfusions, presented with abdominal pain and distention for the past 15 days and complete obstipation for 5 days. Examination revealed significant pallor, pedal edema, moderate ascites with severe abdominal distention and absent bowel sounds, and a left pure motor foot drop.
A working diagnosis of lupus was considered. Her ANA was 4+ fine speckled with Anti-SSA and Anti-SSB (Anti-Ro and Anti-La) positivity on Extractable nuclear antigen (ENA) by immunoblot; urine examination revealed 3000 mg of proteinuria with active sediments, altered renal functions (creat – 1.99 mg/dl previous values were 0.4 mg/dl), and elevated erythrocyte sedimentation rate (104 mm/h) and C-reactive protein (215 mg/l). Hemoglobin was 7.5 gm/dl with normal platelet (1,80,000/dl) and leukocyte count (11,500/dl). She had hypoproteinemia (4.6 g/dl) with hypoalbuminemia (2.2 g/dl) and hypogammaglobulinemia (1 gG-6.1 g/dl), hypokalemia (2.1 mEq/L), metabolic acidosis with normal anion gap (14 mEq/L) and elevated amylase (273U/L), and lipase (203U/L) (both >3 ULN (Upper limit of normal). Her complements were low (C3 – 21 g/ml and C4 – 5 g/ml), but anti-dsDNA levels were normal. Testing for cryoglobulins was negative.
Considering rapidly progressive renal failure and severe lupus, she was pulsed with 15 mg/kg of methylprednisolone, and correction of hypokalemia was started. Gastrointestinal rest was given in view of possible pancreatitis and obstruction; obstipation gradually resolved over a week.
Although she never complained of sicca symptoms, parotid tenderness necessitated an ultrasound revealing altered echotexture of both parotids and submandibular glands, with multiple hypoechoic areas, multiple hyperechoic reflections, and indistinct posterior borders. Elastography revealed significant alterations in the gland echotexture. Despite an emphatic denial of sicca symptoms, Schirmer's test was positive.
Her renal functions normalized after pulse methylprednisolone, and a CECT (contrast-enhanced computed tomography) abdomen did not reveal any evidence of pancreatitis/enteritis/mesenteric vasculitis.
A renal biopsy revealed diffuse proliferative glomerulonephritis (DPGN), interstitial nephritis with IgM, IgG, and C3 positivity (C1q and IgA negative) on immunofluorescence; a minor salivary gland biopsy showed a focal lymphocytic sialadenitis with a focus score of 3 [Figure 1].
|Figure 1: (a) Section shows labial salivary gland with two lymphocytic foci (arrows). The surrounding salivary glands are unremarkable (H and E, ×200). (b) Section shows three glomeruli with diffuse endocapillary proliferation (arrows) and mild lymphocytic interstitial infiltrate (block arrow). (H and E, ×200). (c) Section shows a glomerulus with endocapillary proliferation, polymorph infiltration (asterix), wire loop lesion (arrow), and a hyaline thrombus (block arrow) (H and E, ×400). (d) Ultrasound of the parotids showing altered echotexture, multiple hypoechoic areas with multiple hyperechoic reflections, unclear posterior borders suggestive of parotitis. (e) Parotid elastography revealing altered elastography with a very high strain ratio and an elastography score of 4|
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Anemia was attributable to anemia of chronic disease and hypokalemia and acidosis attributed to renal tubular acidosis (RTA), secondary to interstitial nephritis. The ascites were transudative and attributed to severe hypoalbuminemia. Evaluation for foot drop revealed pure motor neuropathy of bilateral ulnar, common peroneal, and posterior tibial nerves.
A final diagnosis of primary Sjogren's syndrome (SS) with proliferative glomerulonephritis, RTA, and pure motor neuropathy was made, and she was initiated on 1 mg/kg of steroids and monthly cyclophosphamide according to NIH protocol.
Primary SS is a multisystem autoimmune disorder, which primarily affects the exocrine glands, especially the lacrimal and salivary, causing the quintessential sicca symptoms synonymous with the disorder (>95% of patients).
Our patient did not have sicca symptoms but had positive anti-SSA and Anti-SSB antibodies, interstitial nephritis-RTA, negative anti-dsDNA, and no C1q positivity on immunofluorescence (IF). This and parotid tenderness prompted us to do an ultrasound of parotids and submandibular glands. Salivary gland ultrasonography is an easy to learn, rapidly executable, inexpensive, point of care modality that is highly sensitive (45.8%–91.6%) and specific (73%–98.1%) for diagnosing SS. There is also a significant agreement between an abnormal salivary ultrasound and a positive biopsy and vice versa; the combination of a positive ultrasound and a presence of anti-SSA/Ro allowed classification according to American- European Consensus Group Criteria (2002), American College of Rheumatology (ACR) (2012), and ACR-European league against rheumatism (EULAR) (2016) criteria.
Renal involvement in SS is rare in most large retrospective studies, but a few prospective studies, especially one from India, have shown the prevalence in up to 50% of patients with primary SS; yet glomerulonephritis is rare and presents acutely, unlike the more common tubulointerstitial nephritis; that is almost invariably present when the kidneys are involved and are mostly asymptomatic and insidious. DPGN is even rarer and has been found in only 4% of the renal biopsies performed. Rituximab is preferred for patients with altered renal functions and proliferative glomerulonephritis; however, high-dose steroids and cyclophosphamide were chosen in the present case based on economic viability and good response in case reports.
The peripheral nervous system is not that commonly involved in primary SS, with a prevalence of 2%–60% in various studies. There is a paucity of reports with pure motor mononeuritis multiplex, though motor involvement is seen in up to 5% of the patients. There are case reports of patients responding to high-dose glucocorticoids and IV cyclophosphamide.
Hypogammaglobulinemia considered uncommon in primary SS can be seen in up to 15% of the patients and can be a harbinger of transformation to lymphoma or an underlying immunodeficiency; our patient did not give any history of recurrent infections, and imaging and biopsy done did not suggest lymphoma. Nonspecific proteinuria with hypogammaglobulinemia may occur in patients with massive proteinuria and maybe the reason for hypogammaglobulinemia in our patients.
Although there was no evidence of pancreatitis on imaging, she had significantly elevated amylase and lipase levels and responded well to steroids. Patients with primary SS have a higher risk of having both clinical and subclinical acute pancreatitis, which response well to glucocorticoids.
This case highlights the importance of salivary gland ultrasound in the diagnosis of primary SS, especially in those presenting with rare/atypical manifestations like ours with DPGN, pure motor neuropathy, and hypogammaglobulinemia, even in the absence of sicca symptoms.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that their name and initials will not be published, and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
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Conflicts of interest
There are no conflicts of interest.
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