Interstitial lung disease in rheumatoid arthritis: Current concepts in pathogenesis, diagnosis and therapeutics

Table 1 Prevalence of rheumatoid arthritis-interstitial lung disease

Ref.	Number of patients	Study type	ILD (%)
Perez-Dorame et al[111]	34	Cross-sectional	34
Giles et al[154]	177	Cross-sectional	33
Yin et al[29]	71	Retrospective	24.9
Chen et al[10]	103	Cross-sectional	61
Solomon et al[155]	48	Retrospective	31
Richman et al[156]	274	Cross-sectional	3.6
Zou et al[157]	110	Cross-sectional	42.7
Mohd et al[158]	63	Cross-sectional	44
Al-Ghamdi et al[159]	74	Retrospective	10
Teh et al[160]	154	Cross-sectional	6.5
Bharadwaj et al[161]	140	Cross-sectional	9.29
Zrour et al[162]	75	Cross-sectional	49.3

ILD: Interstitial lung disease.

Table 2 Risk factors for interstitial lung disease in rheumatoid arthritis

	Factors
Environmental	Cigarette smoking
	Occupational exposure (silica)
Demographic	Male sex
	Age (≥ 65 yr)
Genetic	HLA-DRB1 alleles
Clinical	RA duration
	Anti-CCP (high titers)
	RF (high titers)
Medications	Methotrexate
	Leflunomide
	Sulfasalazine
	TNF-α inhibitors

RF: Rheumatoid factor; HLA-DRB1: Human leukocyte antigen-DRB-1; Anti-CCP: Anti-cyclic citrullinated peptide; Anti-TNF: Anti-tumor necrosis factor; RA: Rheumatoid arthritis.

Table 3 Pharmacological agents implicated in the development of interstitial lung disease in rheumatoid arthritis patients

Pharmacological agent	Relevant information
DMARDs
MTX	Long-term frequency of MTX-induced ILD is 0.43%[35]
	Incidence is 3.78/1000 patients[56]
	Risk factor for ILD in RA patients (RR = 7.81)[33]
LFN	Increases the risk of developing ILD[46]
	Mortality of 19% in patients with LFN-induced ILD[47]
AZA	Complication of interstitial pneumonia after treatment with AZA[52]
TNF-α inhibitors	Mortality is 32% in patients with ILD treated with TNF-α inhibitors[57]
Etanercept	Incidence of etanercept-induced ILD is 0.6%[73]
Infliximab	Incidence of infliximab-induced ILD is 0.5%[74]

DMARDs: Disease-modifying antirheumatic drugs; MTX: Methotrexate; ILD: Interstitial lung disease; RA: Rheumatoid arthritis; RR: Relative risk; LFN: Leflunomide; AZA: Azathioprine; TNF-α: Tumor necrosis factor-α.

Table 4 Histological and clinical classification of idiopathic interstitial pneumonias

Histologic pattern	Clinical-Radiological-Pathological Diagnosis
Usual interstitial pneumonia	Idiopathic pulmonary fibrosis/COP
NSIP	NSIP
Organizing pneumonia	COP
Diffuse alveolar damage	Acute interstitial pneumonia
LIP	LIP

From: ref.[107], American Thoracic Society; European Respiratory Society. Am J Respir Crit Care Med 2002; 165: 277-304. COP: Cryptogenic fibrosing alveolitis; NSIP: Non-specific interstitial pneumonia; LIP: Lymphoid interstitial pneumonia.