Prevalence and risk factors of active tuberculosis in patients with rheumatic diseases: a multi-center, cross-sectional study in China

Figures & data

Figure 1. Screening process for ATB in enrolled patients with rheumatic diseases. ATB=active tuberculosis, IGRA=interferon-gamma release assay, TST=tuberculin skin test. *Whether to choose Chest X-ray or CT scans was decided by the clinicians based on each patient's clinical condition.

Table 1. Categorization of the study population.

Diagnostic Category	Criteria
Microbiologically /histologically confirmed TB	A biological specimen was positive by smear microscope, culture or Xpert MTB/RIF and (or) histological changes in lesions were typical, such as caseous necrosis, epithelioid granulomatous and etc.
Clinically diagnosed TB	Patients had characteristic symptoms, including fever, cough, chest pain, night sweats, weight loss and etc. Laboratory and imaging findings were highly suggestive for MTB and diagnostic anti-TB treatment was effective.
Clinically indeterminate	A final diagnosis of tuberculosis was neither confirmed nor reliably excluded
ATB excluded	Bacteriological or histological examinations showed no evidence for ATB. If the patient was originally suspected of TB, an alternative diagnosis should be identified and eventually confirmed by diagnostic therapy.

Figure 2. Flowchart of the study. ATB=active tuberculosis.

Table 2. General characteristics of 13550 enrolled patients with rheumatic conditions.

	ATB	Non-ATB
	Number of patients/Total number (%)	Number of patients/Total number (%)
Male	30/105 (28.6)	3234/13445 (24.1)
Median age [IQR], year	42 [28–53]	45 [33–56]
Education level
College and above	28/83 (33.7)	2939/11081 (26.5)
Senior high school	15/83 (18.1)	2549/11081 (23.0)
Junior high school	25/83 (30.1)	3372/11081 (30.4)
Primary school	13/83 (15.7)	1696/11081 (15.3)
Illiterate	2/83 (2.4)	525/11081 (4.7)
Type of rheumatic diseases
RA	19/105 (18.1)	5097/13445 (37.9)
SLE	41/105 (39.0)	2918/13445 (21.7)
SS	9/105 (8.6)	1271/13445 (9.5)
SSc	5/105 (4.8)	472/13445 (3.5)
MCTD	0/105 (0)	329/13445 (2.4)
PM	1/105 (1.0)	220/13445 (1.6)
DM	2/105 (1.9)	521/13445 (3.9)
TA	4/105 (3.8)	156/13445 (1.2)
BD	7/105 (6.7)	304/13445 (2.3)
Other systemic vasculitis†	2/105 (1.9)	206/13445 (1.5)
AS	15(/105 (14.3)	1173/13445 (12.9)
PsA	0/105 (0)	217/13445 (1.6)
Median duration of rheumatic diseases [IQR], month	24 [7–72]	14 [1–50]
Medications within the past two years
GCs	79/103 (76.7)	8768/13189 (66.5)
Immunosuppressants	70/103 (68.0)	8770/13235 (66.3)
Biological agents	12/101 (11.7)	1834/13195 (13.9)
Complications
Diabetes Mellitus	7/105 (6.7)	528/13226 (4.0)
Malignancy	0/104 (0)	66/13246 (0.5)
Chronic renal failure	1/104 (1.0)	88/13346 (0.7)
Silicosis	0/103 (0)	13/13338 (0.1)
Exposure to TB	1/86 (1.2)	160/13307 (1.2)
With evidence of previous TB	18/98 (18.4)	458/13381 (3.4)

SLE=systemic lupus erythematosus. RA=rheumatoid arthritis. SS=Sjogren’s syndrome. SSc=systemic sclerosis. MCTD=mixed connective tissue diseases. PM=polymyositis. DM=dermatomyositis. TA=Takayasu's arteritis. BD=Behcet’s disease. SpA=spondyloarthropathy. GCs=glucocorticoids.

†Including giant cell arteritis (GCA), polyarteritis nodosa (PAN), granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA).

Table 3. Prevalence of ATB among patients with rheumatic diseases.

Type of rheumatic diseases	Number of patients with ATB	Total number of patients	Prevalence of ATB (/100,000 population) (95% CI)
SLE	41	2959	1386 (964-1807)
RA	19	5116	371 (205-538)
SS	9	1280	703(245-1161)
SSc	5	477	1048(131-1966)
MCTD	0	329	/
PM	1	221	453(0- 1344)
DM	2	523	382 (0-913)
TA	4	160	2500(55- 4945)
BD	7	311	2251(593- 3908)
Other systemic vasculitis*	2	208	962(0-2299)
AS	15	1749	858(425-1290)
PsA	0	217	/
Overall prevalence	105	13550	775(634-937)
Standardized overall prevalence	105	13550	882(706-1057)

SLE=systemic lupus erythematosus. RA=rheumatoid arthritis. SS=Sjogren’s syndrome. SSc=systemic sclerosis. MCTD=mixed connective tissue diseases. PM=polymyositis. DM=dermatomyositis. TA=Takayasu's arteritis. BD=Behcet’s disease. SpA=spondyloarthropathy.

*Including giant cell arteritis (GCA), polyarteritis nodosa (PAN), granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA).

Table 4. Classification of ATB patients with rheumatic diseases (WS196-2017).

Tuberculosis classification	N (%) (n=105)
Pulmonary TB	88 (83.8)
Lung	62 (59.0)
Lung + lymph nodes	3 (2.9)
Lung + Pleura	2 (1.9)
Lung + meninges	2 (1.9)
Lung + bone	1 (1.0)
Lung + skin	1 (1.0)
Lung + skin+ bone	1 (1.0)
Lung + Pleura + pericardium	1 (1.0)
Lung + meninges + liver + spleen	1 (1.0)
Pleura	10 (9.5)
Miliary TB	2 (1.9)
Miliary TB + meninges	1 (1.0)
Bronchia	1 (1.0)
Extra-pulmonary TB	17 (16.2)
Lymph nodes	5 (4.8)
Bone	5 (4.8)
Urinary system	2 (1.9)
Meninges	1 (1.0)
Skin	1 (1.0)
Uvea	1 (1.0)
Bone + meninges	1 (1.0)
Liver + spleen	1 (1.0)

Table 5. Potential risk factors of ATB in patients with rheumatic diseases in univariate analysis.

			Univariate analysis
	ATB	Non-ATB	OR (95% CI)	P value
	n=84	n=11565
Gender
Female	62	9100	1
Male	22	2465	1.310 (0.804-2.135)	0.279
Age(years) Median [IQR]	42 [29–54]	46 [34–56]	0.982 (0.966-0.997)	0.020
Type of rheumatic diseases
RA	15	4238	1
SLE	37	2783	3.756 (2.058-6.857)	<0.001
BD	7	276	7.166 (2.898-17.720)	<0.001
Other rheumatic diseases*	25	4268	1.655 (0.871-3.143)	0.124
Duration of rheumatic diseases (months), Median [IQR]	26 [7–74]	16 [1–59]	1.001 (0.998-1.004)	0.415
Use of CTX within past two years
No	65	9953	1
Yes	19	1612	1.805 (1.080-3.017)	0.024
Use of MMF within past two years
No	72	10694	1
Yes	12	871	2.046 (1.106-3.785)	0.022
Use of MTX within past two years
No	66	8040	1
Yes	18	3525	0.622 (0.369-1.049)	0.075
Use of AZA within past two years
No	76	11191	1
Yes	8	374	3.150 (1.509-6.574)	0.002
Use of LEF within past two years
No	69	9137	1
Yes	15	2428	0.818 (0.467-1.432)	0.482
Use of CsA within past two years
No	81	11295	1
Yes	3	270	1.549 (0.486-4.936)	0.459
Use of FK506 within past two years
No	83	11388	1
Yes	1	177	0.775 (0.107-5.599)	0.801
Duration of GCs≥30mg/d within past two years (weeks)
0-4	56	9870	1
>4	28	1695	2.912 (1.844-4.596)	<0.001
With evidence of previous TB
No	69	11180	1
Yes	15	385	6.993 (3.943-12.403)	<0.001

SLE=systemic lupus erythematosus. RA=rheumatoid arthritis. SS=Sjogren’s syndrome. SSc=systemic sclerosis. MCTD=mixed connective tissue diseases. PM=polymyositis. DM=dermatomyositis. TA=Takayasu's arteritis. BD=Behcet’s disease. SpA=spondyloarthropathy. CTX=Cyclophosphamide. MMF=Mycophenolate mofetil. MTX=Methotrexate. AZA=Azathioprine. LEF=Leflunomide. CsA=Cyclosporine A. FK506=Tacrolimus.

*Including Sjogren's syndrome (SS), systemic sclerosis (SSc), mixed connective tissue disease (MCTD), polymyositis (PM), dermatomyositis (DM), Takayasu arthritis (TA), giant cell arthritis (GCA), polyarteritis nodosa (PAN), granulomatosis with polyangiitis (GPA), microscopic polyarteritis (MPA), eosinophilic granulomatosis with polyangiitis (EGPA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA).

Table 6. Potential risk factors of ATB in patients with rheumatic diseases in multivariable logistic regression.

			Multivariable analysis
	ATB	Non-ATB	OR (95% CI)	P value
	n=84	n=11565
Type of rheumatic diseases
RA	15	4238	1	<0.001
SLE	37	2783	2.722 (1.437-5.159)	0.002
BD	7	276	5.261 (2.071-13.365)	<0.001
Other rheumatic diseases*	25	4268	1.320 (0.684-2.549)	0.408
Use of AZA within past two years
No	76	11191	1
Yes	8	374	2.095 (0.986-4.450)	0.054
Duration of GCs≥30mg/d within past two years (weeks)
0-4	56	9870	1
>4	28	1695	2.031 (1.247-3.309)	0.004
With evidence of previous TB
No	69	11180	1
Yes	15	385	6.185 (3.487-10.969)	<0.001

RA=rheumatoid arthritis. SLE=systemic lupus erythematosus. BD=Behcet’s disease. AZA=azathioprine. GCs=glucocorticoids.

*Including Sjogren's syndrome (SS), systemic sclerosis (SSc), mixed connective tissue disease (MCTD), polymyositis (PM), dermatomyositis (DM), Takayasu arthritis (TA), giant cell arthritis (GCA), polyarteritis nodosa (PAN), granulomatosis with polyangiitis (GPA), microscopic polyarteritis (MPA), eosinophilic granulomatosis with polyangiitis (EGPA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA)

Data availability statement

The data that support the findings of this study are available from the corresponding author, Prof. Xiaoqing Liu, upon reasonable request.