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CASE REPORT
Ahead of print publication  

Tjalma syndrome: A rare manifestation of systemic lupus erythematosus


1 Internal Medicine Resident, Sheikh Shakhbout Medical City, Abu Dhabi, UAE
2 Rheumatology Fellow, Sheikh Shakhbout Medical City, Abu Dhabi, UAE
3 Gastroenterology Fellow, Sheikh Shakhbout Medical City, Abu Dhabi, UAE
4 Rheumatology Consultant, Sheikh Shakbout Medical City, Abu Dhabi, UAE
5 Medical Student, Khalifa University, Abu Dhabi, UAE
6 Gastroenterology Consultant, Sheikh Shakbout Medical City, Abu Dhabi, UAE

Date of Submission06-Apr-2022
Date of Acceptance13-Jun-2022
Date of Web Publication02-Aug-2022

Correspondence Address:
Raven Haan,
Khalifa University, Abu Dhabi
UAE
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/injr.injr_70_22

  Abstract 


Tjalma syndrome, also known as pseudo-pseudo Meigs' syndrome, is a rare manifestation of conditions in patients with systemic lupus erythematosus (SLE). The syndrome is characterized by the presence of ascites, pleural effusion, and an elevated cancer antigen-125 (CA-125) level. We present the case of a 27-year-old female patient admitted in 2021 without any comorbidities, who presented with unintentional weight loss, gastrointestinal upset, and ascites. Further evaluation showed elevated CA-125 levels and pleural effusions, with no atypical cells. The patient was initially treated with antiemetics, intravenous fluids, antibiotics, and total parental nutrition with no improvement in her symptoms or laboratory parameters. The results of an autoimmune workup met the criteria for the classification of SLE. After extensive investigation, she was diagnosed with Tjalma syndrome. She was subsequently treated with corticosteroids and hydroxychloroquine, resulting in the rapid resolution of the patient's nausea and emesis, and discharge from the hospital. Her ascites resolved over 4 weeks. Prednisolone was tapered down and azathioprine was added as a steroid-sparing agent. The patient eventually had complete remission of her symptoms, as well as remarkable improvements in her laboratory results. However, 8 months after her initial diagnosis, the patient showed signs of increasing SLE activity with lupus nephritis, anemia, and leukopenia, despite being compliant with her treatment regimen. The patient was initiated on oral prednisolone (1 mg/kg) and azathioprine was replaced with mycophenolate mofetil, which resulted in significant improvement of clinical and laboratory parameters within 3 weeks. Cases of Tjalma syndrome, and specifically, this presentation, are rarely reported in the literature. We present this condition to raise awareness about both the presenting symptoms and therapeutic options for Tjalma syndrome.

Keywords: Pseudo-pseudo Meigs' syndrome, systemic lupus erythematosus, Tjalma syndrome



How to cite this URL:
Alhmoudi A, Almarzooqi A, Alahmad M, Al Muhairi A, Diab S, Haan R, Elsayed K. Tjalma syndrome: A rare manifestation of systemic lupus erythematosus. Indian J Rheumatol [Epub ahead of print] [cited 2022 Aug 20]. Available from: https://www.indianjrheumatol.com/preprintarticle.asp?id=353151


  Introduction Top


The triad of an ovarian tumor, ascites, and pleural effusion is known as Meigs' syndrome. When the ascites and pleural effusion are associated with tumors other than ovarian, it is referred to as pseudo-Meigs' syndrome. Tjalma described Tjalma syndrome, or pseudo-pseudo Meigs' syndrome (PPMS), as a rare clinical condition in systemic lupus erythematosus (SLE) patients, characterized by ascites, pleural effusion, and elevated cancer antigen-125 (CA-125) levels in individuals without any associated malignant or benign tumors. Physicians need to be aware that the presence of elevated cancer markers such as CA-125, with ascites and pleural effusion, does not necessarily equate to a cancer diagnosis, and to thoroughly investigate alternate causes such as Tjalma syndrome. This may prevent unnecessary anxiety and surgical interventions, as Tjalma syndrome is treatable with immunosuppressant medications. We describe the case of a 27-year-old female who presented with symptoms of Tjalma syndrome and was not a known case of SLE. A literature search regarding Tjalma syndrome could only identify 13 other cases, bringing the total to 14 cases. This informs fellow physicians of symptoms of Tjalma syndrome and makes them aware to include it as a differential when ascites, pleural effusions, and elevated CA-125 are present, so patients could get appropriate treatment and avoid unnecessary invasive investigations or surgery.


  Case Report Top


The patient was a previously healthy 27-year-old Emirati female. She presented to our hospital in 2021 with a 3-month history of nausea, recurrent emesis, and watery diarrhea with no blood or mucus. These symptoms were associated with upper abdominal pain with abdominal distention, poor oral intake, dehydration, and fatigue with an unintentional weight loss of 5 kg. The patient denied any fever, ulceration, sicca manifestations, skin rashes, inflammatory joint pain, yellowish sclera, or lower limb edema. Moreover, she had no family history of malignancies, liver disease, or autoimmune diseases. The patient also reported that her menstrual cycles had been irregular in the past 3 months, with minimal spotting. Her physical examination on presentation was negative for any mucocutaneous ulcerations or rashes. Her abdomen was distended and soft, with right iliac fossa tenderness, shifting dullness, and a positive fluid thrill. No organomegaly could be appreciated on examination, and the examination was negative for any presentation of lymphadenopathy.

The patient had been previously admitted to multiple hospitals and had undergone various investigations, including an endoscopy and colonoscopy. Her endoscopy had shown mild-to-moderate erythematous gastritis and reflux esophagitis, whereas her colonoscopy showed mild left-sided patchy erythematous colitis with inconclusive biopsy results. Initial laboratory testing showed albumin levels of 32 g/L, hypokalemia of 2.42 mmol/L, and creatinine of 120 μmol/L (53-97.2 μmol/L). Liver function tests and thyroid tests came back as normal, and the patient was negative for beta-human chorionic gonadotropin. A chest X-ray showed small, bilateral pleural effusions [Figure 1], as did a computerized tomography (CT) chest exam. An abdominal CT with contrast revealed diffuse thickening of the entire colon and terminal ileum, moderate-to-gross ascites, and multiple pelvic, retroperitoneal, and mesenteric lymph nodes. Kidneys were normal in size and showed enhancement with mild-to-moderate hydroureteronephrosis [Figure 2]. A CT pyelogram demonstrated no evidence of mass lesions, periureteric nodules, or filling defects with the renal collecting system. Pelvic ultrasound was also unremarkable. Diagnostic abdominal paracentesis revealed a serum ascites albumin gradient of 1.1 with no malignant cells. Fluid analysis revealed a white cell count of 245 × 106/L with 89.8% mononuclear cells, suggesting exudative ascites. Cytology was negative for malignancy or granuloma, so no peritoneal biopsy was conducted to avoid unnecessary invasive testing. Based on her symptoms and findings, we invested autoimmune markers, which demonstrated a positive ANA 1:640 homogenous pattern, mildly elevated anti-double-stranded (DS) DNA (51.9 U/mL), low C3 (0.75 g/L), normal ESR (3 mm/h), and negative extractable nuclear antigen (ENA) profile. Ferritin was also within the normal range, but she had a mild elevation of C-reactive protein, a positive Coombs test with high lactate dehydrogenase levels, negative ENA profile, and an antiphospholipid antibodies screen meeting the 1997 American College of Rheumatology classification criteria and 2019 EULAR/ACR classification criteria for SLE with current SELENA-SLEDAI: 4/105, in keeping with moderate disease activity.
Figure 1: Presenting chest X-ray at admission

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Figure 2: Abdominal CT on admission. CT: Computerized tomography

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The patient was initially treated with antiemetics, intravenous fluids, proton-pump inhibitors, and antibiotics, in addition to total parenteral nutrition (TPN). When the diagnosis of SLE was confirmed, hydroxychloroquine (HCQ) 5 mg/kg was initiated in addition to pulse methylprednisolone (500 mg daily for 3 days) on the 5th day of admission. She was then shifted to oral prednisolone (1 mg/kg). Since starting on HCQ and corticosteroids, the patient gradually improved, with the resolution of her nausea and ascites, and the resumption of good oral intake. TPN was stopped and the patient was discharged home with HCQ and prednisolone 35 mg (1 mg/kg).

During the patient's follow-up visits, we were able to gradually taper her glucocorticoids by adding azathioprine 100 mg daily (2 mg/kg) as a steroid-sparing agent, and the patient had complete resolution of her symptoms. Her laboratory results showed remarkable improvements including the normalization of anti-DS DNA [Table 1]. A month after discharge, the patient contracted COVID-19, however, the patient was able to self-isolate at home, and denied any shortness of breath, difficulty in breathing, chest pain, fever, or cough. None of the patient's symptoms relapsed during this time and continued follow-ups after the patient's self-isolation period ended showed maintained improvement in laboratory results and cessation of initial presenting symptoms.
Table 1: Patient laboratory reports

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However, 8 months after her initial diagnosis, the patient's urinary protein creatinine ratio increased gradually to 1.29 g/g (<0.5 g/g), and her 24 h urinary protein was estimated to be 0.91 gm/day. She also developed severe leukopenia with a white blood cell (WBC) 1.55 × 109/L, along with anemia with hemoglobin of 7.3 g/dl, despite being compliant with her treatment regimen. Her anti-DS-DNA titers increased and her C3 levels were low, indicating an increase in her SLE disease activity with probable lupus nephritis.

Nephrology was consulted and ordered a kidney biopsy, however, the patient refused. She was started empirically on mycophenolate mofetil (MMF) 1 g twice daily, in addition to 1 mg/kg oral prednisolone.

Three weeks after initiation of prednisolone and MMF, her laboratory parameters showed significant improvement including the normalization of her complements, WBC, and protein/creatinine ratio.


  Discussion Top


Tjalma syndrome, or PPMS, is a rare manifestation of patients with SLE, defined by the presence of ascites, pleural effusions, and an elevated CA-125 level with no associated benign or malignant ovarian tumor.[1] PPMS is managed by treating the underlying SLE with standard immunosuppressive regimens. A positive outcome was observed in our patient following treatment, with gradual resolution of the ascites and pleural effusions, and normalization of CA-125.

The pathogenesis of Tjalma syndrome is not clear, but it is hypothesized that uncontrolled severe inflammation may be one of the causes through lympho-aggregation, and an immune complex deposition on the peritoneal membrane generating a local inflammatory reaction or a vasculitic phenomenon involving the peritoneal vessels.[2] Massive ascites are an uncommon initial presentation of SLE and have rarely been reported in the literature.[3],[4] Usually, ascites in such patients are a resulting consequence of active disease, nephrotic syndrome, protein-losing enteropathy, and constrictive pericarditis.[5] CA-125 is a glycoprotein that reacts with epithelial tumor cells of ovarian cancer;[6] however, it has been detected in other mesothelial cells, such as the peritoneum, pleura, pericardium, epithelium of  Fallopian tube More Detailss, lungs, breast, prostate, and conjunctiva,[7] in addition to various clinical conditions such as early pregnancy, ascites, menstruation, nephrotic syndrome, endometriosis, leiomyoma, congestive heart failure, cirrhosis, rheumatoid arthritis, tuberculosis, and SLE.[8],[9],[10] Elevation of CA-125 in SLE may be related to activation of cytokines such as interleukin 1 and interferon γ, which increases the expression of CA-125 in human peritoneal mesothelial cells.[10] Our patient improved dramatically with pulse methylprednisolone, HCQ, and eventually the steroid-sparing agent azathioprine, highlighting that successful treatment may be achieved in such cases without the need for aggressive immunotherapy or surgical interventions. We conducted a literature review to find other cases of Tjalma syndrome and their treatment, as well as if the patient had a previously known diagnosis of SLE. [Table 2] demonstrates that many of these cases occur in individuals who have not yet been diagnosed with SLE, so we must be aware that Tjalma syndrome may be the first presenting symptom of SLE in certain individuals. Corticosteroids, HCQ, and azathioprine appear to be the mainstay of treatment in these individuals; however, there has also been reported use of rituximab, MMF, leflunomide, and cyclophosphamide, demonstrating a wide variety of successful treatment options for such patients.
Table 2: Supplementary data on other cases of Tjalma syndrome found in the literature

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  Conclusion Top


Our case report and literature search on similar cases demonstrate the need for Tjalma syndrome to be a differential diagnosis for patients presenting with ascites, pleural effusions, and elevated CA-125 levels. We also highlight that Tjalma syndrome can be the first presentation of SLE. If a diagnosis of SLE with Tjalma syndrome is confirmed, our case and review of the literature demonstrate that these symptoms can be resolved with treatment of the underlying autoimmune disease and control of the subsequent inflammation. The presenting patient was left seeking a diagnosis and treatment for 3 months before her admission under our care. Ruling out malignancy remains the first priority, but it is also important to raise awareness about Tjalma syndrome among rheumatologists, as well as gastroenterologists and gynecologists.

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

Nil.

Conflicts of interest

There are no conflicts of interest.













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