Tuberculous polyserositis in endemic areas with an emphasis on empiric therapy: A case report : Medicine: Case Reports and Study Protocols

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Clinical Case Report

Tuberculous polyserositis in endemic areas with an emphasis on empiric therapy

A case report

Munguti, Jeremiah MBChB, BSc Anatomya; Mutua, Victor BSc Physiologya,*; Cheruiyot, Isaac BSc Anatomya; Csefalvay, Chris von MA(Oxon), FRSPHb; Opare-Addo, Paul Family Medicinec; Kiko, Nduku MBChB, MMED-IMEDd; Wanjiru, Rosemary MBChB, MMED-IMEDd

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Medicine Case Reports and Study Protocols 3(4):p e0221, April 2022. | DOI: 10.1097/MD9.0000000000000221
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Abstract

Rationale: 

Polyserositis describes contemporaneous inflammation of multiple serous membranes accompanied by effusions in serous cavities. It has been associated with different aetiologies, including autoimmune diseases, endocrine diseases, neoplasia, drug-associated cases, and infectious diseases, such as tuberculosis.

Patient concerns: 

We report the case of a 34-year-old woman who presented with abdominal swelling for 8 months, fatigability, and shortness of breath for 2 months. She denied a history of lower-limb swelling, orthopnea, paroxysmal nocturnal dyspnoea, or right upper quadrant pain. She had no history of cigarette smoking, prior treatment for tuberculosis, malignancy, or contact with someone known to have tuberculosis (TB). On examination, she had a weak pulse, muffled heart sounds, and ascites.

Diagnosis: 

Polyserositis was suspected following visualization of fluid in the peritoneal, pleural, and pericardial cavities on imaging.

Interventions: 

The patient underwent pericardiocentesis and ascitic taps. The patient also received spironolactone, prednisolone, and paracetamol. Despite repeated ascitic tapping and use of diuretics, fluid continued to accumulate until the initiation of empiric anti-TB drugs (rifampicin, isoniazid, pyrazinamide, and ethambutol), as noted from the elevated levels of adenosine deaminase (pleural fluid-46.30U/L) and living in an endemic area for tuberculosis (Kenya).

Outcomes: 

Three weeks after the initiation of anti-TB drugs, the ascites and pericardial and pleural effusions resolved. Two months after discharge, the patient showed marked improvement, with no residual fluid noted in the serous cavities on imaging.

Lessons learnt: 

We report a case of extrapulmonary TB presenting with polyserositis (pericardial, pleural, and ascitic fluid) with elevated adenosine deaminase levels when the traditional Ziehl Neelsen staining yielded negative results. Good clinical judgment and more novel diagnostic tools are necessary to avoid unnecessary delays in initiating definitive management.

1. Introduction

Polyserositis (PS) is an effusive inflammation of serous membranes, such as the peritoneum, pericardium, and pleura at the same time.[1] It is commonly seen in autoimmune diseases (especially familial Mediterranean fever), endocrine diseases such as hypothyroidism, infectious diseases such as tuberculosis (TB), neoplasia, and in a drug-associated context (primarily with clozapine and tyrosine kinase inhibitors).[2,3] TB presents with serositis, which is referred to as serosal tuberculosis, a common extrapulmonary manifestation of TB, especially in highly endemic areas.[4] However, Mycobacterium tuberculosis was isolated in 50% of patients with PS, and TB was the final diagnosis in 25% of 642 pleural effusions studied in northern Spain over a 6-year period.[5,6] This makes the diagnosis of isolated TB polyserositis challenging and may delay the eventual initiation of definitive treatment. It is important to note that, in many cases, the aetiology of PS remains unknown.

Here, we present a case of PS in a 34-year-old immunocompetent with no history of TB and negative workup for Mycobacterium tuberculosis, except for elevated adenosine deaminase (ADA) and mild leukocytosis in the peritoneal fluid. The patient’s PS resolved rapidly in response to empiric anti-TB therapy.

F1
Figure 1.:
Electrocardiogram tracing showing low amplitude QRS complexes.

2. Case presentation

2.1. History and examination

A 34-year-old woman presented to our hospital with abdominal swelling for 8 months, easy fatigability, and shortness of breath for 2 months. No history of lower limb swelling, orthopnea, paroxysmal nocturnal dyspnea, or right upper quadrant pain was reported. The patient had no history of cough, intermittent fever, or unintentional weight loss. Notably, however, she had a history of pleural effusion 2 years prior, which resolved spontaneously without an established cause.

The patient denied a history of cigarette smoking, prior treatment for TB, malignancy, or contact with someone known to have TB. Her family history was negative for familial cancer, connective tissue, or autoimmune disorders. She had no known exposure to occupational hazards nor was she hypertensive or diabetic. The patient was nulliparous, and her gynecologic/obstetric history was unremarkable.

Upon examination, the patient was alert and not in obvious distress. She had mild pallor without jaundice, lymphadenopathy, wasting, finger clubbing, or cyanosis. She had tachycardia at 102 beats per minute, with normal blood pressure (98/66 mm Hg) and body temperature.

On palpation, the abdomen was not tender, but had a stretched transverse umbilicus. Fluid thrill and shifting dullness were present, suggesting ascites. No hepatosplenomegaly was observed, and bowel sounds were normal.

There was a dull percussion note and decreased vesicular sounds in the right lower lung field, with a respiratory rate of 20 breaths/ min. The rest of the respiratory examination results were normal.

She had a weak, rapid, but regular pulse. Upon auscultation, the apex beat was not displaced; however, the heart sounds were muffled. No murmurs were heard. She did not have a hyperactive precordium but had engorged neck veins.

F2
Figure 2.:
Echocardiography showing pericardial fluid.

2.2. Investigations

2.2.1. Laboratory work-up.

Laboratory workup indicated mild anemia (Hemoglobin: 10.7 g/dL) with normal total and differential leukocyte and platelet counts. Results of liver function tests, renal function tests, and serum electrolyte levels were normal. The total serum protein and albumin levels were normal at 50 and 28 g/dL, respectively. Notably, her CA-125 level was elevated at 109 U/mL, but her CEA and CA 19-9 were normal. Her C-reactive protein level was normal. Her plasma lactate dehydrogenase level was mildly elevated at 283 U/L (reference range, 109-245). She tested negative for HIV, HBsAg, HCV Ab, antinuclear antibodies, rheumatoid factor and Covid-19.

Ascitic fluid tapping was performed, yielding a strawcolored tap with thin, watery consistency. Smear examination revealed a hypocellular smear comprising dispersed lymphocytes. There was no evidence of malignancy or acid-fast bacilli infection. The serum ascites albumin gradient was calculated as 0.4 g/dL.

Pericardial fluid analysis revealed a high lactate dehydrogenase levels (2447U/L), slightly elevated ADA at 31.0 IU/L (0-30), and normal total protein. Cytology revealed paucicellular smears consisting of histiocytes in a haemorrhagic background. Atypical or malignant cells were not observed. Ziehl-Neelsen staining was performed to test for acid-fast bacilli, which was negative. The pericardial fluid culture yielded no bacterial growth.

F3
Figure 3.:
Computed tomography scan: Sagittal plane of the lower thorax and abdomen showing pericardial effusion and ascites.

Pleural fluid ADA was notably elevated at 46.30U/L (cutoff of 40 IU/L is useful for identifying significantly elevated ADA levels and favoring the diagnosis of TB in serous fluid).

GeneXpert of the pleural fluid was performed at another facility, and the results were positive for TB. It is important to note that this result returned late after anti-TB treatment was initiated.

2.2.2. Electrocardiogram.

Normal sinus rhythm with lowvoltage QRS complexes consistent with pericardial effusion (Fig. 1).

2.2.3. Imaging.

Echocardiography: Moderate-severe pericardial effusion with collapsed right atrium in diastole. Her left ventricular ejection fraction was 73%. No regional wall motion abnormalities were observed (Fig. 2).

Computed tomography revealed ascites, right pleural effusion, and pericardial effusion. (Fig. 3, Fig. 4)

2.3. Interventions and outcome

The patient underwent several pericardiocentesis procedures and ascitic taps. The initial pericardiocentesis drained 900 mL mildlyhemorrhagic serous fluid, with subsequent drain removal between 300 and 500mL of clear serous fluid. Despite multiple pericardiocentesis procedures, fluid continued to accumulate until the initiation of anti-TB drugs. Based on Kenyan TB guidelines, anti-TB medications were administered following a clinical diagnosis of extrapulmonary TB.

F4
Figure 4.:
Computed tomography scan: Transverse plane showing a right pleural effusion and pericardial effusion.

To manage her symptoms, she was administered spironolactone 25g OD, prednisolone 20g TID, and paracetamol 1g TID.

The patient was treated with empiric anti-TB treatment with a 2-month intensive phase of rifampicin, isoniazid, pyrazinamide, and ethambutol followed by a 4-month continuation phase of rifampicin and isoniazid (RH). Pyridoxine was also administered to prevent the adverse effects of isoniazid. Three weeks after the initiation of TB treatment, ascites and pericardial and pleural effusions resolved. Two months after discharge, the patient showed marked improvement, with no residual fluid noted in the serous cavities on ultrasound imaging. Laboratory work-up showed normal results. The patient was followed-up for 1.5 years and there was no recurrence of symptoms or accumulation of fluid in the pericardial, pleural, or abdominal cavity after initiation and completion of anti-TB medication. The patient did not develop any adverse effects to medication given.

3. Discussion

PS is characterized by inflammation of multiple serous membranes with effusion in the serous cavities.[1] PS may be part of a wider syndromic presentation of an underlying disease (TB, systemic lupus erythematosus, familial Mediterranean fever, certain malignancies, asbestosis, silicosis), complications of chest surgery, radiation therapy, and certain drugs. Rarely, it is idiopathic.[3,7] Most reports of serositis in the literature describe cases involving one or 2 serous membranes, with the majority being cases of pleural effusion, ascites, or constrictive pericarditis secondary to TB or as sequelae of autoimmune diseases such as systemic lupus erythematosus, mixed connective tissue disease, or familial Mediterranean fever.[7-12] Here, we present a case of polyserositis with the simultaneous involvement of all 3 body cavities.

Our patient, who initially presented with symptomatic pleural effusion 2 years prior that had resolved without any definitive treatment, presented once again, but this time with fluid accumulation in the peritoneal, pleural, and pericardial cavities. The 3 serosae were extensively involved, with no clear-cut underlying pathology. All investigations for a connective tissue disorder proved negative, as did Ziehl Neelsen staining for Mycobacterium. Based on Kenyan TB guidelines, anti-TB medications were administered following a clinical diagnosis of extrapulmonary TB.

The diagnosis of extrapulmonary tuberculosis is frequently based on histopathological investigations, but histological findings are often non-specific.[13] The gold standard for confirming the presence of Mycobacteria tuberculosis is gene Xpert/PCR testing, but this method is often unavailable in many resource-limited settings. ADA is a much simpler and more widely available test. Estimation of ADA levels in serous fluid is an easy and reliable method to confirm the diagnosis of peritoneal tuberculosis.[14,15] ADA levels in serous fluid above 40IU/L are diagnostic for tuberculous serositis, with 87% sensitivity and 89% specificity.[16,17]

In the present case, the patient also had elevated serum CA-125 levels. CA-125 is a useful marker for epithelial ovarian cancer. It is secreted from mesothelial cells lining the pleura, pericardium, peritoneum, and areas of inflammation, including serositis secondary to TB.[9,18,19] Benign gynaecological pathologies, including endometriosis, leiomyomas, pelvic infections, and pregnancy, may result in elevated serum CA-125 levels.[20,21] Malignant causes of elevated CA-125 levels include acute leukaemia, especially in young children; non-Hodgkin’s lymphoma with serosal involvement; gastric carcinoma; and mesothelioma.[22-24] Our case report aligns with those of previous studies that showed an association between elevated serum CA 125 levels and peritoneal tuberculosis.[9,25,26] Serous fluid CA-125 levels have been observed to return to normal within a few months after the commencement of specific anti-TB therapy.[27,28]

Although the initial workup for TB was negative (i.e., microscopy for acid-fast bacilli), the patient’s symptoms, together with her elevated ADA levels and residency in an endemic area for TB (Kenya), started empirical anti-TB treatment. The response to treatment, including the resolution of her polyserous effusions and the late positive gene Xpert for TB, confirmed this diagnosis.

Author contributions

Conceptualization: Jeremiah Munguti, Victor Mutua.

Investigation: Victor Mutua.

Writing - original draft: Jeremiah Munguti, Victor Mutua, Isaac Cheruiyot.

Writing - review & editing: Jeremiah Munguti, Victor Mutua, Isaac Cheruiyot, Chris von Csefalvay, Paul Opare-Addo, Nduku Kiko, Rosemary Wanjiru.

References

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Keywords:

empiric therapy; polyserositis; tuberculosis

Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.