Volume 5, Jul - Sep 2022
Case Report:
Author’s Affiliation:
1- Department of Immunology and Rheumatology, Bharati Vidyapeeth University Medical College Hospital & Research Centre, Pune (India)
Sunil V. Kapur, Email: sunilvkapur@gmail.com
Received on: 12-Jul-2021
Accepted for Publication: 02-Jul-2022
Article No: 21712lPN074520
PDF - Full Text

Primary Sjogren's (pSS) is a chronic multisystem autoimmune disease predominantly affecting the exocrine glands. Extra glandular involvement might involve the musculoskeletal, renal, pulmonary, haematological and the central nervous system. Hematological abnormalities are common in Sjögren's syndrome, including anemia, leukopenia, thrombocytopenia, and lymphoproliferative disordersCytopenias in pSS are usually mild. Clinically significant immune-mediated cytopenia may be a rare initial manifestation of an pSS especially in children. The present case reports a fourteen-year-old girl with a rare atypical manifestation of bicytopenia as an initial presenting feature of pSS. Unexplained cytopenias in any patient should alert a physician to investigate for pSS.

Keywords: Bicytopenia, Sjögren’s syndrome, Schirmer’s test


Primary Sjogren's syndrome (pSS) is a chronic multisystemic autoimmune disease characterized by lymphocyctic infiltration of the exocrine glands (specifically the salivary and lacrimal glands) leading to sicca symptoms. Extra glandular manifestations are frequently underdiagnosed and include vasculitis, neuropathy, glomerulonephritis, arthritis, hematological abnormalities and interstitial lung disease1. Clinically important cytopenias may be the presenting feature of an pSS and is rarely reported in children (Table 1). The pathophysiology and prevalence of cytopenia in SS is still an area of ongoing research. Sometimes a patient can present with severe anemia, leukopenia or thrombocytopenia prior to the development of sicca symptoms. This case reports an unusual presentation of pSS and hence should be included in the differential diagnosis in patients with unexplained cytopenias.


A 14-year-old female child presented with complaints of weakness, pallor and mucosal bleeding since last two months of duration. There was no history of fever, oral ulcers, weight loss, rash, icterus, joint swelling, or history of drug intake. General examination revealed severe pallor, petechial rashes on both arms, dry eyes with no evidence of lymphadenopathy, organomegaly, parotid gland enlargement and dental caries. Laboratory investigations revealed anemia and thrombocytopenia (hemoglobin - 6.8 g/dL, white blood cell count -7100/mm3 and platelet count- 24,300/mm3) with elevated acute phase reactant (ESR-43 mm/hr). Peripheral blood smear was suggestive of normocytic normochromic red blood cells. Direct Coombs test was negative. Infectious profile (HIV, hepatitis B and C, Ebstein Barr virus, Cytomegalovirus) was negative. Renal function, liver function, urine routine, CT chest and abdomen, and Vitamin B12 levels were within normal limits.  LDH levels were elevated [860 U/L (313-618 U/L)].  Bone marrow examination was suggestive of   normal marrow morphology with mild erythroid hyperplasia with normal megakaryopoesis. Autoimmune workup revealed positive Antinuclear antibodies (1/640 -speckled fluorescence pattern), negative anti-dsDNA, normal complement (C3, C4) levels, strongly positive anti-Ro/SSA (96.3U) and anti-La/SSB (82.3U), positive rheumatoid factor and negative Antiphospholipid (APLA) antibodies. Schirmer’s test was significantly positive (2 mm in right eye and 3 mm in left eye). Parents did not consent for salivary gland biopsy. Our patient fulfilled the 2017 ACR EULAR (American College of Rheumatology-European League Against Rheumatism) Classification diagnostic criteria for pSS. A final diagnosis of pSS with autoimmune bicytopenia was considered and he was initiated on oral prednisolone (1 mg/kg/day) and azathioprine (2 mg/kg/day) with gradual improvement in bicytopenia and ESR levels. At 2 months of follow-up period, corticosteroid was tapered successfully with remission in his bicytopenia and normalization of ESR (hemoglobin -11.2 g/dL, WBC -8900/mm3 and platelets count -1.6 lakh/mm3, ESR -5 mm/hr).

Table 1. Characteristics of reported immune cytopenias in Sjogren’s syndrome reported in all patients


Age /Gender

Hematological manifestations



Schattner et al. (2000)

a)  32 yrs/Female

Autoimmune hemolytic anemia

Weakly Positive


b) 77 yrs/Female


Weakly Positive


c) 58 yrs/Female




Klepfish et al. (2001)

    40 yrs/ female

Neutropenia, thrombocytopenia


Asymptomatic, didn’t receive immunosuppressant

Kamath et al. (2011)

    32 yrs/Female

Anemia and thrombocytopenia



Khattri and Barland (2012)

a) 59 yrs/Female

Autoimmune hemolytic anemia, Thrombocytopenia

Not reported


b) 26 yrs/Female




Komaru et al. (2013)

    36 yrs/Female

Autoimmune hemolytic anemia



Yu W et al. (2017)

   59 yr, female




Martínez et al. (2018)

   50 yrs/Female

Anemia and thrombocytopenia




Sicca symptoms are characteristic for diagnosis of pSS. However, extraglandular involvement is common and protean which may precede or exist with the sicca manifestations (as in our case).  Haematological manifestations of pSS are not uncommon, but they are mostly recognized as mild laboratory abnormalities of no clinical significance in patients whose pSS is already diagnosed 2,3 . In an Australian cohort of 27 pSS patients, hematological manifestations was detected in 40% of patients 2. In contrast, Sandhya P et al reported 25 patients (7.5%) having hematological manifestations in a cohort of 332 pSS patients in South India 3 . Break down of hematological manifestations in the study were as follows: thrombocytopenia (n=14), leucopenia (n=2), monoclonal gammopathy of undetermined significance (n=4), pseudolymphoma (n=2), Kikuchi’s disease (n=1) and unexplained hepatosplenomegaly(n= 2).  Unlike our case, pSS is usually characterized by a mild normocytic normochromic anaemia, mild thrombocytopenia and leucopenia which are not clinically significant enough to require treatment 2. Immune-mediated anemia, red cell aplasia, and thrombocytopenia have been reported in pSS 4.  Similar to our case, bicytopenia or pancytopenias can be the sole presenting feature in pSS 4, 5.  Presence of autoantibodies against various cell lineage could be one of the triggering factor for cytopenias 5.  Based on literature, Antineutrophil and anti-RBC antibodies were observed in 45% and 22% of patients with pSS respectively 6,7   . Patients with pSS with positive anti-Ro antibodies (similar to our patient) had a higher frequency of hematological involvement such as anemia and thrombocytopenia 8 . The treatment of pSS involves management of the sicca symptoms and immunosuppression for extraglandular manifestations (corticosteroids, azathioprine, cyclophosphamide, methotrexate, cyclosporin, danazol, rituximab, plasmapheresis or immunoglobulin in refractory cases) 15.


We highlight this case to increase awareness amongst physicians regarding children presenting with unexplained cytopenias should be specifically screened for Sjogren's syndrome. Conversely, periodic hematological review of patients with Sjogren's syndrome is critical to pick up clinically significant cytopenias.



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8.      Rudolph SE, Kouba M, Hrdlicka P. Severe corticoid-refractory autoimmune thrombocytopenia associated with mixed connective tissue disease (Sharp’s syndrome). Treatment with rituximab. Dtsch Med Wochenschr. 2009 [in German].

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10.    Klepfish A, Friedman J, Schechter Y, Schattner A. Autoimmune neutropenia, thrombocytopenia and Coombs positivity in a patient with primary Sjögren’s syndrome. Rheumatology (Oxford) 2001; 40:948-9.

11.    Kamath V, Prabhakar B, Veena, Lachikarathman D. Sjogren’s thrombocytopenia. J Assoc Physicians India 2011; 59:114-5.

12.    Khattri S, Barland P. Primary Sjogren’s syndrome and autoimmune cytopenias: a relation often overlooked. Bull NYU Hosp Jt Dis 2012; 70:130-2.

13.    Komaru Y, Higuchi T, Koyamada R, et al. Primary Sjögren syndrome presenting with hemolytic anemia and pure red cell aplasia following delivery due to Coombs-negative autoimmune hemolytic anemia and hemophagocytosis. Intern Med 2013;52: 2343-6.

14.    Martínez VA, Leal CA, Moreno DC. Alteraciones hematológicas como manifestación inicial del síndrome de Sjögren primario. Rev Colomb Reumatol 2018; 25:55-8.

15.    Schattner A, Friedman J, Klepfish A, Berrebi A. Immune cytopenias as the presenting finding in primary Sjögren’s syndrome. QJM. 2000; 93:825-9.

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