An unusual cause for sicca syndromeUP Kulkarni1, YA Gokhale2, PM Raut1, RR Dargad1
1 Department of Medicine, Lokmanya Tilak Municipal Medical College and General Hospital, Sion, Mumbai, India
2 Department of Rheumatology Services, Lokmanya Tilak Municipal Medical College and General Hospital, Sion, Mumbai, India
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0022-3859.81872
Source of Support: None, Conflict of Interest: None
We present a case of a 47-year-old female who presented with sicca symptoms since three months. As per the Revised International Classification Criteria for Sjögren's syndrome, patient was diagnosed as primary Sjögren's syndrome (SS). Patients with SS are known to have circulating monoclonal immunoglobulins. Serum electrophoresis revealed M band with serum gamma globulin concentration of 46 g/L. Bone marrow aspiration revealed 28% plasma cells. In absence of myeloma-related organ damage, a diagnosis of smouldering myeloma (MM) was made. Patient was treated with thalidomide and dexamethasone. Sicca symptoms resolved with anti-myeloma treatment. Although MM can occur as a complication of SS, MM can also rarely present as SS. In the present case, the short duration of sicca symptoms and response of these symptoms to anti-myeloma treatment support the diagnosis of MM presenting as SS. The present case highlights the importance of serum electrophoresis in patients presenting as SS.
Keywords: Circulating monoclonal immunoglobulins, multiple myeloma, sicca syndrome, Sjφgren′s syndrome
Primary Sjögren's syndrome (SS) is characterized by both T-cell lymphocytic infiltration of the exocrine glands and oligomonoclonal B lymphocyte hyperreactivity. As a result about 20% of patients with SS have circulating monoclonal immunoglobulins.  Patients with circulating monoclonal immunoglobulins have a greater risk of developing hematological malignancies; commonest being lymphoma. Rarely, patients with SS develop multiple myeloma (MM). , However SS can also be the presenting symptom complex for MM.  Early diagnosis and treatment of the underlying MM in such cases result in resolution of sicca symptoms. We present a case of SS which on investigations was also found be smouldering myeloma.
A 47-year-old female was referred to us for dryness of eyes and mouth associated with burning sensation in the eye and difficulty in swallowing since three months. There was no history of fever, joint pain, parotid or submandibular swelling, myalgia, Raynaud's phenomena, cough, hematuria, rash, jaundice, focal neurological deficit or syncopal attacks. There was no significant medical history of past illness. Patient was not on any medications that cause sicca symptoms. The referring physician had performed CT scan of the parotid glands, which revealed enlarged parotids, and fine needle aspiration cytology of the gland detected lymphocytic infiltrate in the salivary gland tissue.
On physical examination, patient was moderately nourished, afebrile, pulse was 92 per minute and regular, blood pressure was 120/80 mm of mercury while the respiratory rate was 16 per minute. There was no pallor, icterus, clubbing, cyanosis, lymphadenopathy, rash or salivary gland enlargement. Jugular venous pressure was normal. Oral mucosa was dry and mucosa over tongue was atrophic. Conjunctival erythema was present. Rest of the systemic examination was unremarkable. Schirmer's I test performed without anesthesia was 3 mm in 5 minutes in both eyes. Joints were not swollen or tender.
Laboratory investigations revealed hemoglobin of 10 g/dL, white cell counts of 6900/mm 3 , platelet count of 330000/mm 3 , erythrocyte sedimentation rate of 110 mm at 1 hour, creatinine 1.3 mg/dL, total bilirubin 0.8 mg/dL, total protein 10.4 g/dL, albumin 2.7 g/dL, globulin 7.7 g/dL, calcium 8.1 mg/dL, phosphorus 8.3 mg/dL, sodium 141 mEq/L and potassium 4.0 mEq/L. Rheumatoid factor, anti-nuclear antibody, anti-Ro and anti -La antibody were negative. Antibodies to Hepatitis C and HIV were negative. Serum angiotensin converting enzyme level was normal. There was no hilar adenopathy on chest x-ray.
Biopsy from lip salivary gland revealed mildly acanthotic squamous epithelium overlying lobules of minor salivary gland tissue with few small lymphocytic aggregates seen around ducts and acini with a focus score of 1. Patient was prescribed methylcellulose eye drops and counseled about dental hygiene.
Serum protein electrophoresis revealed 'M' band in the gamma region (alpha 1 globulins - 6 g/L, alpha 2 globulins - 11 g/L, beta globulins - 14 g/L, gamma globulins - 46 g/L). Serum immunofixation studies revealed monoclonal IgG - lambda gammopathy. Urinary Bence Jones proteins were negative. Bone marrow aspiration revealed 28% plasma cells and the bone marrow biopsy revealed a plasma cell dyscrasia. Skeletal survey was normal.
In addition to methylcellulose eye drops for sicca symptoms, thalidomide and dexamethasone were started. At one month follow-up, patients' sicca symptoms improved. Patient continued this treatment for 18 months and then was lost to follow-up. Three years later patient presented with bone pains. Investigations revealed raised creatinine (2.2 mg/dL), positive urinary Bence Jones proteins, hemoglobin of 5.7 g/dL, WBC count of 4100/mm 3 , ESR of 120 mm, serum protein electrophoresis revealed gamma globulins of 61.3 g/L. Serum-free light chain analysis revealed increased lambda chains (12028 mg/L with kappa to lambda ratio of 0.002). On bone marrow biopsy, there was total replacement of marrow by abnormal plasma cells with CD 138 positivity. Skeletal survey revealed lytic lesions in skull bones. With intravenous hydration, serum creatinine reduced to 0.8 mg/dL. Subsequently patient was treated with bortezomib along with dexamethasone for this relapse. With treatment, gamma globulin levels reduced to 15 g/L, free lambda chain levels reduced to 1290 mg/L with kappa to lambda ratio of 0.32.
Based on the Revised International Classification Criteria for Sjögren's syndrome (SS),  our patient satisfied the diagnostic criteria (4 out of 6 criteria) of primary SS, without autoantibodies. Other conditions associated with sicca symptoms like sarcoidosis, HCV/HIV sialoadenitis were ruled out by investigations.
High serum globulins in patients with SS can be attributed to the circulating monoclonal immunoglobulins that are present in one-fifth of the cases. These patients would be labeled as having monoclonal gammopathy of unknown significance (MGUS).
However quantification of M protein is required for the diagnosis of MGUS. Hence a serum electrophoresis was done. Since gamma globulins were more than 30 g/dL, MGUS was ruled out. A diagnosis of smouldering myeloma was made based on the findings of gamma globulins more than 30 g/L with M band, more than 10% plasma cells on bone marrow aspiration with no symptoms of myeloma-related organ or tissue involvement.
Now that our patient satisfied the criteria for both primary SS as well as smouldering myeloma, we were interested in knowing whether the myeloma was the primary disorder or it was a complication of SS.
There are reports of SS developing into MM, , but we came across only one case report of MM presenting as SS. 
Primary SS is considered as a crossroad disease between autoimmunity and lymphoproliferation.  Circulating monoclonal immunoglobulins in patients with SS represent presence of monoclonal B-cell population with a potential to develop into malignancies, commonest being B-cell lymphomas. Abnormal B-cell stimulation and impaired censoring mechanisms of B cells in SS is responsible for development of malignancies.  In such cases, anti-myeloma treatment does not relieve the sicca symptoms. Also the duration of sicca symptoms prior to the diagnosis of MM is long.
Expression of constitutively high levels of interleukin-6, known to have a critical role in the pathogenesis of autoimmune disorders, is known to occur in MM.  Autoimmune disorders like pernicious anemia,  autoimmune hemolytic anemia  and SS  have been reported with MM. When MM presents as sicca syndrome, the duration of sicca symptoms is short and these symptoms respond well to anti-myeloma treatment.
Since the sicca symptoms, which were present since 3 months, responded to anti-myeloma treatment, we concluded that myeloma was the primary disorder that had presented as SS. The age at presentation and the presenting symptom both were unusual for a diagnosis of MM.
The present case highlights the importance of serum protein electrophoresis while diagnosing SS especially when the duration of symptoms is short.