ILD (Interstitial lung disease) may be an sole organ manifestation of Autoimmune Rheumatic diseases

1. When to call immunologist in
ILD clinic?
Marwa Abo Elmaaty Besar
Lecturer Of Internal Medicine
(Rheumatology Immunology Unit)
Mansoura University

2. Introduction:
• The lung can be the first manifestation of a CTD (preceding the onset
of a definite autoimmune disease by years) as the dominant or even
as the sole organ involvement during an autoimmune disease.
• Interstitial lung disease is often associated with rheumatic diseases.
• Its early diagnosis and management are not only difficult, but also
crucial, because it is associated with major morbidity and mortality
and can be the first cause of death in ARDs.
• Currently, the gold standard in the diagnosis and management of ILD
is the Multidisciplinary Team (MDT),

5. J Intensive Care Med. 2015;30(7):392-400.
It shows a considerable heterogeneity in incidence and prevalence,
severity depending on the underlying rheumatic disease.
Incidence of autoimmune
ILD

6. Clinical signs
Autoantibodies
Instrumental
exam
How to Recognize Them?
Diagnostics 2020, 10, 20

7. Clinical signs

14. Laboratory Exams

15. Autoimmunity
exam
First
second
Autoantibodies
General lab
exam
General exam
• CBC
• ESR, CRP
• ALT, AST
• S. Creatinine
• CPK, LDH
• C3,C4
• SPEP
First line
Autoimmunity exam
• ANA
• RF
• ACCP
• AntidsDNA
• Anti-sm
• ANCA (P,C)
• Anti-RO
• Anti-LA
• Anti-RNP
• SCL70
• Anti-centromere
• Anti-Jo1
Second
Autoimmunity exam
• Rare Ab
• MAAs
• Pm/Scl75kD
• Pm/Scl100kD
• (AMA)M2 ab
• MSAs
• AntiJo1
• Anti-Mi2
• Anti-melanoma
• (anti-
MDA5)
• TIF1
• Anti-HMGCR

16. Diagnostics 2020, 10, 20

17. Instrumental Exams

18. First-Line Instrumental Exams:-
• RP Nail fold Capillaroscopy
• SjS
Salivary gland US
Sialo-scintigraphy
Schirmer’s test
Unstimulated Salivary Flow
Rate Test (USFRT)

19. First-Line Instrumental Exams:-
• Pulmonary Function Tests (PFTs),
follow up
• High-Resolution Computed
Tomography (HRCT)
Diagnostics 2020, 10, 208

20. Second-Line Instrumental Exams
• The most important is biopsy, performed depending on the tissue
involved.
Lung biopsy; to assess the ILD pattern.
Minor salivary gland biopsy; in the diagnosis of ILD underlying SjS.
The kidney and the upper and lower respiratory tract; in AAV.
Muscle biopsy in the diagnosis of IIMs.
kidney biopsy in the diagnosis of SLE.
• Several exams (e.g., echography, electromyography, magnetic
resonance imaging) in order to choose the appropriate tissue for
confident diagnosis.

22. What are the main risk factors for the development of ILD
in ARDs?1
ARDs, in particular, systemic sclerosis, rheumatoid arthritis, and anti-
synthetase syndrome, have to be considered important risk factors for
the development of ILD.
In the presence of ARDs, the presence of some autoantibodies (anti-
JO1, anti-PL 7, anti-PL12, anti-SSA Ro, anti-MDA 5, anti-Scl70, anti-
PM/Scl, anti-Th/To) increase the risk of developing ILD.
Some gene variants are associated with a greater risk of developing
ILD, particularly for some forms, such as usual interstitial pneumonia.

23. What are the main risk factors for the development
of ILD in ARDs?2
In the case of a patient suffering from Systemic sclerosis, there are specific
risk factors for the development of ILD, such as
 Male gender,
 A diffuse form of the disease.
The presence of anti-scl70 antibodies.
In patients with Rheumatoid arthritis, the risk of developing ILD increases
in
Males,
Smoking patients,
With an older age of onset.
The duration of disease.
The titre of anti-citrulline antibodies.

24. What should be the monitoring timing and frequency
of pulmonary symptoms in the patient with ARD?
1. Pulmonary symptoms in the ARD patient should be assessed at each visit.
2. Timing and frequency of pulmonary symptoms monitoring in the ARD
patient depend on the specific rheumatic disease.
3. In the event of worsening respiratory symptoms in a patient with ARD, a
high-resolution chest CT scan should be performed.
4. Respiratory function tests and carbon monoxide alveolar–capillary
diffusion test (DLCO) should be performed every 12 months in patients
with ARD, in case of Systemic sclerosis every 6–12 months.

25. What should be the monitoring timing and frequency
of pulmonary symptoms in the patient with ARD?
5. Pulmonary symptoms of patients with Systemic sclerosis should be
monitored every 6 months in case of progressive rheumatic disease.
6. Respiratory function tests and carbon monoxide alveolar–capillary
diffusion test (DlCO) should be performed every 12 monthsin the
absence of proven ILD.
In the presence of clinical (systemic sclerosis) or
Laboratory (predisposing autoantibodies) risk factors

26. What should be the monitoring timing and frequency
of pulmonary symptoms in the patient with ARD–ILD?
1. In case of patients with ARD and ILD, it is necessary, depending
on the severity,
To evaluate pulmonary symptoms every 3–6 months,
Carry out spirometry tests every 3–6 months,
Carry out carbon monoxide alveolar–capillary diffusion tests (DLCO),
perform six-minute walking test (6MWT), and perform echocardiogram
(ECHO) every 6–12 months.
2. Possible appearance or progression of ILD must be evaluated, in
relation to the disease, by high-resolution CT scan of the chest
as symptoms vary, in the presence of crackles or worsening of
functional tests.

27. Bosello et al.2021
doi: 10.3389/fmed.2021.732761

29. Home message:-
• ILD can be the leading cause of death for some ARD, and the exclusion of any
systemic ARD in any freshly diagnosed ILD is mandatory according to current
guidelines.
• The importance of multidisciplinary approaches has been consolidated in the
clinical practice, and it is of utmost important to keep such an approach for
diagnosis, therapy and follow-up.
• Implement multidisciplinary management is the organization of joint training
courses between rheumatologists, pulmonologists, and radiologists, followed by
the creation of shared clinics between rheumatologists and pulmonologists, the
sharing of diagnostic classification criteria of both ARD and ILD among the
rheumatological and pneumological community.
• Short, easy-to-consult checklists can help untrained physicians better address
these pathologies in the wait of more robust, international guidelines.

30. Reference:
• Solomon JJ, Fischer A. Connective Tissue Disease-Associated Interstitial Lung Disease: A Focused Review. J Intensive Care Med.
2015;30(7):392-400. doi:10.1177/0885066613516579.
• Ha YJ, Lee YJ, Kang EH. Lung Involvements in Rheumatic Diseases: Update on the Epidemiology, Pathogenesis, Clinical Features, and
Treatment. Biomed Res Int. 2018;2018:6930297. Published 2018 May 8. doi:10.1155/2018/6930297
• Cavagna, L.; Trallero Araguas, E.; Meloni, F.; Cavazzana, I.; Rojas-Serrano, J.; Feist, E.; Zanframundo, G.; Morandi, V.; Meyer, A.; Pereira da
Silva, J.A.; et al. Antisynthetase antibodies specificities: Impact on clinical spectrum time course of Antisynthetase syndrome. J. Clin. Med.
2019, 8, 2013.
• Guisado Vasco, P.; Silva, M.; Duarte, M.A.; Sambataro, G.; Bertolazzi, C.; Pavone, M.; Martin-Garrido, I.; Martin-Segarra, O.; Luque-Pinilla,
J.M.; Santilli, D.; et al. Quantitative assessment of interstitial lung disease in Sjögren’s syndrome. PLoS ONE 2019, 14, e0224772.
• Harrison, M. Erythrocyte sedimentation rate and C-reactive protein. Aust. Prescr. 2015, 38, 93–94.
• Cutolo, M.; Sulli, A.; Smith, V. How to perform and interpret capillaroscopy. Best Pract. Res. Clin. Rheumatol.2013, 27, 237–248.
• Sebastiani, M.; Manfredi, A.; Vukatana, G.; Moscatelli, S.; Riato, L.; Bocci, M.; Iudici, M.; Principato, A.;Mazzuca, S.; Del Medico, P.; et al.
Predictive role of capillaroscopic skin ulcer risk index in systemic sclerosis: A multicentre validation study. Ann. Rheum. Dis. 2012, 71, 67–70.
• Chaudhuri, N.; Spencer, L.; Greaves, M.; Bishop, P.; Chaturvedi, A.; Leonard, C. A review of the multidisciplinary diagnosis if Interstitial Lung
Diseases: A retrospective analysis in a single UK specialist centre. J. Clin. Med. 2016, 5, 66.
• Barohn, R.J.; Dimanchkie, M.M.; Jackson, E.C. A pattern recognition approach to the patient with a suspected myopathy. Neurol. Clin. 2014,
32, 569–577.
• Nilsson, B.; Ekdahl, K.N. Complement diagnostics: Concepts, indications, and practical guidelines. Clin. Dev. Immunol. 2012, 2012, 962702.