Isolated Splenic Tuberculosis: A Systematic Review

doi:10.61336/jccp/25-02-59

Abstract

Tuberculosis (TB) has been a major cause of morbidity and mortality worldwide despite significant advancement in the diagnosis and treatment of the disease. Isolated involvement of spleen without any other organ involvement is rare in immunocompetent individuals and thus poses a diagnostic challenge. Isolated splenic tuberculosis may not present with characteristic symptoms and therefore diagnosis is often missed. Histopathological examination is the diagnostic modality of choice. Splenic TB patients respond well to standard ATT. Surgical intervention is indicated for medical therapy failure and complications. Splenic abscess even in immunocompetent individuals, should raise the suspicion of tuberculous etiology. The aim of this study is to present and share a review on the cases of isolated splenic tuberculosis published in the PubMed in last 10 year so as to gain understanding about the clinical presentation, diagnostic challenges and early treatment of isolated tuberculosis.

Keywords

Splenic tuberculosis

Isolated

Tuberculosis

Immunocompetent

INTRODUCTION

Tuberculosis (TB) has been a major cause of morbidity and mortality worldwide despite significant advancement in the diagnosis and treatment of the disease. Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis which primarily affects the lungs but can ^also affect other sites as well. According to the latest Global Tuberculosis Report 2024 released by WHO, an estimated 10.8 million people fell ill with tuberculosis worldwide in 2023 in which India accounted for 26% of global TB burden¹.

Among all the cases of tuberculosis in India, extrapulmonary tuberculosis (EPTB) accounts for 20-24% of cases and is higher in the immunocompromised people as compared to general population ².

EPTB can either be primary (at the site of infection) or secondary (disseminated) due to hematogenous or lymphatic spread of bacteria or due to reactivation of latent TB, ingestion of infected sputum or spread locally from adjacent organ³. The diagnosis of EPTB is often delayed or even missed due to insidious clinical presentation, paucibacillary nature and lack of diagnostic facilities in the resource limited settings or made at an advance stage when complications have already set in.

Among EPTB, 12% of cases account for abdominal Tuberculosis⁴. Abdominal tuberculosis may involve gastrointestinal tract, peritoneum, mesenteric lymph node, viscera or genitourinary tract ⁵.

Usually, splenic tuberculosis only manifests as a part of miliary or abdominal tuberculosis. Isolated involvement of spleen without any other organ involvement is rare in immunocompetent individuals and thus poses a diagnostic challenge. Isolated splenic tuberculosis may not present with characteristic symptoms and therefore diagnosis is often missed^6.

Epidemiologically, only a few isolated case reports of splenic tuberculosis are available from different region making the prevalence uncertain.

The aim of this study is to present and share a review on the cases of isolated splenic tuberculosis published in the PubMed in last 10 year so as to gain understanding about the clinical presentation, diagnostic challenges and early treatment of isolated tuberculosis.

MATERIALS AND METHODS

The search strategy, inclusion and exclusion criteria were defined before the search.

The systematic research of the literature was performed on PubMed by applying last 10 year filter in dec 2024 according to PRISMA (Preferred Reporting Items for Systemic review and Meta analysis). Specific MeSH words were Splenic tuberculosis, isolated, tuberculosis, spleen, splenic abscess.

All case report, case series and letter to editor about the case of isolated splenic tuberculosis were included in this study.

Inclusion criteria include

Case report, case series and letter to editor about the patients with isolated splenic tuberculosis. (no other organ is involved).
Full text available.
Complete information is available regarding patient demographics, diagnostic modalities of splenic tuberculosis.

Exclusion criteria include

Patient with history of pulmonary tuberculosis or diagnosed with pulmonary tuberculosis.
Unavailability of full text.
Patients of abdominal (except isolated splenic) or miliary tuberculosis.
Case reports with incomplete information.

Data was extracted by one author independently and then studied. Titles/ abstracts considered potentially relevant were retrieved for review of the full manuscript. The list of full manuscript meeting inclusion criteria was then studied.

RESULTS

We retrieved 38 manuscripts meeting our criteria from the search and 23 manuscripts were included in the study. There were 21 case report and 2 letter to editor citing about the cases of isolated splenic tuberculosis.

S.NO.	AUTHOR	PATIENT AGE/SEX	CHIEF COMPLAINT	Physical examination	INVESTIGATIONS DONE	HIV STATUS	Chest X ray	DIAGNOSIS	AFB	PCR	TREATMENT
1	Rohan R et al, 2024 ⁷	29/F	Low grade fever from 5 months	Splenomegaly	CT shows multiple micro abscess in spleen	Negative	Not mentioned	FNAC shows CG	+	Not done	ATT for 6 months
2	Li C et al, 2024 ⁸	42/M	Epigastric pain and discomfort.	NAD	CT show multiple splenic nodule with calcification.	Negative	Not mentioned	Splenectomy done. HPE shows CG	NA	NA	NA
3	Ranjan R et al, 2024⁹	56/M	Upper abdominal pain and vomitings from 3 months	Not Mentioned	CECT show spleen with single large lesion (abscess)	Negative	Chest Xray show lesion but Negative for CBNAAT for MTB	Emergency splenectomy done due to splenic abscess rupture.HPE shows chronic inflammatory cells and infected hematoma.	-	+	ATT for 6 months
4	Guo HW et al, 2022 ¹⁰	73/M	Weight loss and Fatigue from 2 months.	No splenomegaly	CT scan show single large lesion in spleen	Negative	CT normal	CT guided Biopsy show CG,	+	+	ATT for 6 months
5	Sayyahfar et al, 2022 ¹¹	5.5/F	Fever from 2 weeks	NAD	USG shows multiple micro abscess in spleen CT scan confirmed the findings	Negative	Normal	Open spleen biopsy done. HPE shows CG But QFT and PCR for MTB negative on 1st but came positive in second visit where Crohn’s was also diagnosed.	-	+	ATT for 6 months
6	Chablou et al, 2021 ¹²	62/M	Left hypochondriac pain, low grade fever, anorexia, weight loss from 5 weeks.	Febrile, mildly enlarged tender spleen.	USG shows splenomegaly with multiple lesions.	Negative	Normal	Open splenectomy done. HPE shows CG	+	Not done	ATT for 6 months
7	Lestariet al,2021 ¹³	40/F	Early satiety and epigastric pain from 6 months.	Splenomegaly	CT scan shows splenomegaly with multiple lesions along with Lymph node enlargement of perihilar and paraaortic region.	Negative	Normal	Splenectomy done along with lymph node dissection HPE show CG	NA	NA	ATT started
8	Grover et al, 2021¹⁴	30/F	Fever with chills, rigors, night sweats and headache from 3 months. Left upper quadrant abdominal pain and weakness from 1 month.	Febrile, pallor, non tender firm splenomegaly H/O Diabetes	USG shows splenomegaly with multiple lesions.	Negative	Normal	USG guided FNAC done. shows CG	_	+	ATT given for 6 months.
9	Dey S et al, 2021¹⁵	28/F	Diagnosed case of Hodgkin’s Lymphoma Follow up shows splenic lesion	Lymphadenopathy	PET CT show focal FDG uptake in spleen	Negative	NA	USG core needle biopsy done. HPE show CG	NA	NA	NA
10	Kakaje et al, 2020¹⁶	5/F	H/O fever from 2 months. No H/O cough, rigor, chills, night sweats, pain or any other gastric complaints.	Enlarged spleen, pallor and weight was below 1st percentile	CT show splenomegaly with no focal lesion	Negative	Normal	Open splenectomy done sent for biopsy along with Hilar lymph node shows caveating granulomas. AFB culture positive.	-	NA	ATT for 9 months
11	Marcos- Ramirez ER et al, 2020 ¹⁷	40/M	Fever from 2 months along with weight loss and asthenia	Febrile, Grade 1 Splenomegaly	CT show multiple hypotenuse lesion.	Positive	CT Chest Normal	Done by splenectomy. HPE show CG	+	+	ATT started
12	Metlo et al, 2019¹⁸	8/F	Low grade fever with intermittent abdominal pain from 1 year.	Pallor, thin built, soft non tender distended abdomen with enlarged spleen.	CT show two hypodense area in spleen	Negative	Normal	Done on CT findings of splenic abscess with mesenteric lymphadenopathy along with clinical suspicion.	Not done	Not done	ATT for 12 months.
13	Dhibar et al, 2018 ¹⁹	30/M	Left upper quardant pain, loss of appetite and weight from 3 months. No H/O fever.	Enlarged non tender spleen	CT multiple calcified foci in spleen.	Negative	Normal	Done by FNAC aspirate shows caseous necrosis	+	+	ATT given for 6 months
14	Gupta P et al, 2018 ²⁰	62/F	Case of Acute Pancreatitis diagnosed with splenic lesion. H/O fever and left upper quadrant pain	NAD H/o Diabetic	CT scan show single hypotenuse lesion.	Negative	Not mentioned	Done by USG guided FNAc showing CG	+	Not done	ATT started
15	Sethi et al, 2018^[21]	49/F	Fever from 2 months	Pallor and tender splenomegaly	CT show multiple splenic abscess.	Negative	Normal	10 ml pus aspirated from splenic abscess.	+	Not done	ATT started
16	Khadka and Pradhan, 2017 ²²	22/M	Fever with chills and rigor, left lower chest pain, occasional nausea and vomitings, weight loss from 3 weeks.	Febrile, soft tender left upper quadrant, spleen not palpable	CT show multiple splenic abscess.	Negative	Normal	Done after USG guided aspiration of 30 ml pus aspirated	-	+	ATT given for 6 months
17	Wangai et al, 2017 ²³	26/M	Fever with chills and sweats, weight loss from 1 month. H/O transient cough which resolve	Febrile with no other findings or organomegaly.	CT show multiple splenic nodules	Negative	Normal	Core needle biopsy from spleen. HPE shows multiple CG	+	+	ATT given for 6 months
18	Rao et al, 2017 ²⁴	17/F	Fever from 4 weeks	NAD	FDG-PET show multiple lesion uptake in spleen. USG and MRI normal	Negative	Normal	CT guided core needle biopsy. HPE shows CG	NA	NA	ATT for 9 months
19	Lin et al, 2016 ²⁵	64/F	Abdominal discomfort and nausea from 2 months.	Epigastric tenderness, no hepatosplenomegaly.	CT show single large hypodese lesion	Negative	Normal.	Splenectomy done. HPE shows CG	NA	NA	ATT started
20	Kumar S et al, 2016²⁶	23/F	Fever, weakness, Left hypochondriac pain from 10 months	Abdominal tenderness with no organomegaly	CT show 2 hypodense lesion in spleen	Negative	NA	FNAC inconclusive. Splenectomy done, HPE shows CGs	NA	NA	ATT for 6 months
21	Zhang Y et al, 2016²⁷	58/M	Known case of Acute Leukaemia presents with Nausea, severe abdominal pain and hypotension	NAD	USG show free fluid in abdomen. Splenic rupture.	Negative	Normal	Splenectomy done. HPE shows CGs	-	NA	Treatment given on clinical suspicion. Patient responded
22	Kumar et al, 2015²⁸	51/M	High grade fever and Left sided upper abdominal pain from 3 months.	Moderate tender splenomegaly	CT show single large hypodese lesion	Negative	NA	Done on CT guided FNAC	NA	NA	ATT given for 6 months
23	Raviraj et al, 2015²⁹	63/M	High grade fever with chills, rigour, wight loss, anorexia from 1 month.	Pallor, moderate non tender splenomegaly	CT show splenomegaly with no focal lesion	Negative	Normal	USG guided biopsy from spleen. HPE shows CG	-	+	ATT started.

DISCUSSION

Splenic Tuberculosis (TB) is a rare form of entity having infectious etiology. It was first reported by Coley in 1846 ^[25]. Splenic tuberculosis is generally seen as an opportunistic infection in immunocompromised hosts, or as a part of disseminated pulmonary tuberculosis. However, isolated involvement of spleen in tuberculosis in immunocompetent patients is rare. The incidence of splenic TB is 0.14-0.7% as per autopsy-based studies ³⁰.

Spleen can be involved in two forms. Primary infection is an isolated focus of infection in spleen without any other organ involvement, but the presence of a separate focus signifies a secondary infection[]. Primary infection of spleen is a rare occurrence. Hence, possible misdiagnosis includes splenic carcinoma, lymphoma, metastatic lesion, hemangioma and splenic abscess. Possibility of misdiagnosis increases when there is no history of tuberculosis.

According to study by Dixit et al, splenic involvement was found in only 16 (0.01%) of patients of tuberculosis. Out of these 16 cases 62% were associated with pulmonary TB, and 50% of patients had HIV coinfection³¹.

In this systemic review, out of 23 cases of isolated splenic tuberculosis, one case was HIV positive, one case had acute leukemia, and one case was undergoing chemotherapy for Hodgkin lymphoma, one case was associated with Crohn’s disease, one case was diagnosed during treatment of acute pancreatitis with history of diabetes and one case had a history of Diabetes Mellitus Type II. Thus, in this review, out of 23 cases, 3 cases were immunocompromised.

Out of 23 cases, 11 were males and 12 were females. The age ranged from 5 years to 64 years. The most common clinical manifestations in descending order were fever, upper left quadrant abdominal pain, epigastric pain, weight loss, anorexia, nausea and vomiting. However, in almost all the patients there was no H/O of cough, breathlessness. Also, history of tuberculosis or Anti tuberculosis treatment taken was not present.

The clinical presentation of splenic TB can often be vague and nonspecific, which frequently leads to delayed diagnosis. The diagnosis may be complicated by the absence of tuberculous lesions in other organs, especially in the lungs, from where there is a possibility of hematogenous spread to the spleen (miliary tuberculosis)⁷.

On physical examination, splenomegaly was seen in only 12 out of the 23 cases. Thus, radiological investigations are an important pillar in the evaluation of these patients. Ultrasonography and CT (Computed Tomography) scan are important radiological modalities. Radiological findings are important for arriving at a diagnosis in majority of cases, though histological and/or microbiological evidence is the confirmatory.

The findings in radiological investigations; Ultrasonography (USG) or CT scan in these patients were splenomegaly with either multiple hypodense lesion (11 cases) in spleen or presenting as single lesion (5 cases) or two lesions (2 cases) in spleen. In another 2 cases, radiology showed only splenomegaly with no focal lesions and in 1 case splenic rupture was identified on USG. In the rest of the two cases, Positron emission tomography (PET- CT) was done for suspicion of malignancy. It showed increased uptake of FDG in spleen.

Splenic TB can also lead to serious complications, including hypersplenism, portal hypertension, and even rupture of the spleen.⁹Splenic rupture was seen in 2 out of 23 cases resulting in emergency splenectomy.

The gold standard of diagnosis involves performing a splenectomy or biopsy followed by histopathological examination. Utility of both fine needle aspiration cytology (FNAC) and core needle biopsy (CNB) are debated in literature, FNAC having a lower risk of bleeding but CNB giving a higher biopsy yield.¹⁸

Pathological or microbiological diagnosis is important before initiating treatment for tuberculosis. The diagnosis of isolated splenic TB is typically established through the pathological analysis of a fine needle aspiration cytology or aspirate, splenic biopsy, or specimen obtained from a splenectomy. Splenectomy was done in 9 out of 23 cases and sent for biopsy followed by histopathological diagnosis of Granulomatous lesion.

In 9 cases, splenectomy was done for diagnosis of disease and in 6 cases either CT (2 cases) or USG (2 cases) guided core needle biopsy or open biopsy (2 cases) were taken and sent for histopathological diagnosis. In the rest of 7 cases, FNAC was performed for cytological diagnosis. Preoperative aspiration of the pus and biopsy provides the clinician with a chance to treat the disease without a morbid surgery and helped in organ preservation strategy.

All the 23 cases showed caseating granulomatous lesion under microscope. The presence of acid-fast bacilli can be identified using techniques such as the Ziehl- Neelsen (ZN) stain, polymerase chain reaction methods, and culture. Acid fast bacilli (AFB) stain was positive in 8 cases and negative in 5 cases. The rest of cases did not mention about AFB stain. Out of 23 cases, only 9 had done diagnosis by detecting MTB by molecular methods. Culture was done in 1 case and was found positive for MTB growth.

In most splenic TB cases reported, the treatment approach has involved percutaneous aspiration or splenectomy followed by antituberculosis therapy or only antituberculosis therapy. In all these instances, th Splenic Tuberculosis (TB) is a rare form of entity having infectious etiology. It was first reported by Coley in 1846 ²⁵. Splenic tuberculosis is generally seen as an opportunistic infection in immunocompromised hosts, or as a part of disseminated pulmonary tuberculosis. However, isolated involvement of spleen in tuberculosis in immunocompetent patients is rare. The incidence of splenic TB is 0.14-0.7% as per autopsy-based studies ³⁰.

Spleen can be involved in two forms. Primary infection is an isolated focus of infection in spleen without any other organ involvement, but the presence of a separate focus signifies a secondary infection[]. Primary infection of spleen is a rare occurrence. Hence, possible misdiagnosis includes splenic carcinoma, lymphoma, metastatic lesion, hemangioma and splenic abscess. Possibility of misdiagnosis increases when there is no history of tuberculosis.

According to study by Dixit et al, splenic involvement was found in only 16 (0.01%) of patients of tuberculosis. Out of these 16 cases 62% were associated with pulmonary TB, and 50% of patients had HIV coinfection ³¹.

In this systemic review, out of 23 cases of isolated splenic tuberculosis, one case was HIV positive, one case had acute leukemia, and one case was undergoing chemotherapy for Hodgkin lymphoma, one case was associated with Crohn’s disease, one case was diagnosed during treatment of acute pancreatitis with history of diabetes and one case had a history of Diabetes Mellitus Type II. Thus, in this review, out of 23 cases, 3 cases were immunocompromised.

Out of 23 cases, 11 were males and 12 were females. The age ranged from 5 years to 64 years. The most common clinical manifestations in descending order were fever, upper left quadrant abdominal pain, epigastric pain, weight loss, anorexia, nausea and vomiting. However, in almost all the patients there was no H/O of cough, breathlessness. Also, history of tuberculosis or Anti tuberculosis treatment taken was not present.

The clinical presentation of splenic TB can often be vague and nonspecific, which frequently leads to delayed diagnosis. The diagnosis may be complicated by the absence of tuberculous lesions in other organs, especially in the lungs, from where there is a possibility of hematogenous spread to the spleen (miliary tuberculosis) ⁷.

On physical examination, splenomegaly was seen in only 12 out of the 23 cases. Thus, radiological investigations are an important pillar in the evaluation of these patients. Ultrasonography and CT (Computed Tomography) scan are important radiological modalities. Radiological findings are important for arriving at a diagnosis in majority of cases, though histological and/or microbiological evidence is the confirmatory.

The findings in radiological investigations; Ultrasonography (USG) or CT scan in these patients were splenomegaly with either multiple hypodense lesion (11 cases ) in spleen or presenting as single lesion (5 cases) or two lesions (2 cases) in spleen. In another 2 cases, radiology showed only splenomegaly with no focal lesions and in 1 case splenic rupture was identified on USG. In the rest of the two cases, Positron emission tomography (PET- CT) was done for suspicion of malignancy. It showed increased uptake of FDG in spleen.

Splenic TB can also lead to serious complications, including hypersplenism, portal hypertension, and even rupture of the spleen.⁹Splenic rupture was seen in 2 out of 23 cases resulting in emergency splenectomy.

The gold standard of diagnosis involves performing a splenectomy or biopsy followed by histopathological examination. Utility of both fine needle aspiration cytology (FNAC) and core needle biopsy (CNB) are debated in literature, FNAC having a lower risk of bleeding but CNB giving a higher biopsy yield.¹⁸

Pathological or microbiological diagnosis is important before initiating treatment for tuberculosis. The diagnosis of isolated splenic TB is typically established through the pathological analysis of a fine needle aspiration cytology or aspirate, splenic biopsy, or specimen obtained from a splenectomy. Splenectomy was done in 9 out of 23 cases and sent for biopsy followed by histopathological diagnosis of Granulomatous lesion.

In 9 cases, splenectomy was done for diagnosis of disease and in 6 cases either CT (2 cases) or USG (2 cases) guided core needle biopsy or open biopsy (2 cases) were taken and sent for histopathological diagnosis. In the rest of 7 cases, FNAC was performed for cytological diagnosis. Preoperative aspiration of the pus and biopsy provides the clinician with a chance to treat the disease without a morbid surgery and helped in organ preservation strategy.

All the 23 cases showed caseating granulomatous lesion under microscope. The presence of acid-fast bacilli can be identified using techniques such as the Ziehl- Neelsen (ZN )stain, polymerase chain reaction methods, and culture. Acid fast bacilli (AFB) stain was positive in 8 cases and negative in 5 cases. The rest of cases did not mention about AFB stain. Out of 23 cases, only 9 had done diagnosis by detecting MTB by molecular methods. Culture was done in 1 case and was found positive for MTB growth.

In most splenic TB cases reported, the treatment approach has involved percutaneous aspiration or splenectomy followed by antituberculosis therapy or only antituberculosis therapy. In all these instances, the disappearance of splenic hypodensity and a full response to the medication served as an additional confirmation of the diagnosis of a TB splenic abscess.

Although splenectomy is seldom needed in the treatment of spleen TB, it might become necessary in patients with splenic abscess or spontaneous rupture of the spleen or if the treatment does not yield any response.e disappearance of splenic hypodensity and a full response to the medication served as an additional confirmation of the diagnosis of a TB splenic abscess.

Although splenectomy is seldom needed in the treatment of spleen TB, it might become necessary in patients with splenic abscess or spontaneous rupture of the spleen or if the treatment does not yield any response.

CONCLUSION

Tuberculous involvement of the spleen is a rare manifestation of a common infective pathology caused by Mycobacterium tuberculosis. Misdiagnosis is common, and therefore the diagnosis often gets delayed. Histopathological examination is the diagnostic modality of choice. Splenic TB patients respond well to standard ATT. Surgical intervention is indicated for medical therapy failure and complications. Splenic abscess even in immunocompetent individuals, should raise the suspicion of tuberculousetiology

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