ppt

1. Case summary
S-35 yrs old female pt presented with sob and generalized body swelling 1month duration
• Associated with this she had also orthopnoea of 2 pillow and productive cough of whitish sputum same
duration
• She had exertional dyspnoea and intermittent cough of 2 yrs duration
• She told to have cardiac illness since 3 month back.
• She gave birth 2.5 kg alive male neonate 1 month back
• O-GA-ASL V/s-bp-110/70 PR-96-102 (R) RR-22 T-36.3 spo2 79-81 @ room air 92-94% with 1li of INo2
• CHEST-BBS-over the upper 1/3 of the lung field bilaterally
• fine crepitation posterior lower 2/3 of the lung field bilaterally
• CVS-P2accentuated
• S1 and s2 well heard

2. investigation
RF- 44.48 -3.2x (normal <14)
ANA-1:100
Echo-sever PHTN(RVSP-68MMHG) with RV systolic dysfunction(TAPSE-15 MM) EF-60%
,NO chamber dilatation
Chest CT-SCAN-diffuse bilateral pulmonary fibrosis with pulmonary arterial HTN
Radiology side comment- pulmonary HTN fibrosing NSIP pattern
It also shows fibrosing mediastinitis characterized with soft tissue attenuation encased
the pulmonary artery and aorta

3. Introduction
A contemporary joint research statement of the ERS/ATS proposed criteria for
IPAF as an opening move in a trial to uniformly describe and categorize a subset of
patients with IIP that exhibit evidence of autoimmunity without meeting criteria
for a defined CTD.
A significant proportion of patients with ILD manifest autoimmune features, but do
not fulfill the diagnostic criteria for a definite CTD.

4. Interstitial Pneumonia With Autoimmune
Features(IPAF)

5. Introduction cont…
In 2015, the European Respiratory Society (ERS) and American Thoracic Society (ATS)
“Task Force on undifferentiated Forms of CTD-associated ILD ” proposed classification
criteria for a so-called research category of Interstitial Pneumonia with Autoimmune
Features (IPAF).
The joint consensus opinion was made possible via an international expert panel of
 thirteen pulmonologists
four rheumatologists
one thoracic radiologist, and one pulmonary pathologist

6. Introduction cont…

7. Etiology
• ILD comprises of a large group of idiopathic diffuse processes that affect the lung parenchyma
• CTD-ILD represents one of the most common causes of ILD Along with IPF they both represent the
majority of ILDs
• Since CTD-ILD typically follows a better clinical course compared to IPF, and
• hence therapies differ substantially between them, an accurate diagnosis is critical
• Up to 30% of newly diagnosed ILD will be due to CTD
• This underscores the importance of investigating all patients with ILD for possible underlying CTD.

8. Epidemiology
up to 25% of patients with features of a systemic autoimmune disease do not fulfil the ACR
classification criteria for CTD
• On the contrary, in the absence of a defined CTD, 10-20% of patients with idiopathic
interstitial pneumonia have systemic symptoms and serological abnormalities suggestive of an
autoimmune process
• Therefore experts from different medical specialties across the globe have conceptualized this
entity as an undifferentiated CTD-associated ILD, lung-dominant CTD, and autoimmune
featured ILD, using different but overlapping criteria and terminology.

9. Epidemiology…
• The prevalence of IPAF varies between 7 and 34% of all ILDs depending mainly on the
population studied and the patient recruitment profile
• With regards to demographic characteristics, the mean age varies from 60 to 65 years,
with balanced gender,
• although some studies reported a younger mean age (∼55 years) and a
• predominance of white non-smoking women

10. Epidemiology…
 IPAF were mostly found in two clusters with a heterogeneous clinical
presentation—
the cluster of “younger African-American females with elevated antinuclear
antibody titres” and in the cluster of “elderly Caucasian male smokers, with severe
honeycombing”.
In a recent study the presence of a UIP pattern at HRCT and/or histopathology was
associated with a poor outcome as compared to a non UIP pattern among patients
with IPAF, although in general the diagnosis of IPAF was associated with a better
outcome than IPF

11. Pathophysiology
• The pathophysiology of idiopathic interstitial pneumonia with autoimmune features
(IPAF) remains evasive, as no specific studies have been conducted, and it is
hypothesized that pathways involved in IPF or CTD-ILD would be involved in
IPAF.
• It is generally considered that pathophysiological studies are challenging to design in
the absence of clear diagnostic boundaries, and especially in the lack of consensus
regarding IPAF being an entity

12. History and Physical
Typically the first manifestation of ILD is
 the onset of progressive breathlessness with exertion,
a persistent non-productive cough, or
 pulmonary symptoms associated with another disease, such as a connective tissue
disease.

13. Evaluation
Prior to the consensus criteria for idiopathic interstitial pneumonia with
autoimmune features (IPAF), there were four different proposed terminologies in
various articles used to describe non-typical ILD entities:
• 1) Undifferentiated CTD-ILD
• 2) Lung dominant-connective tissue disease
• 4) Autoimmune-featured interstitial lung disease (AIF-ILD)

14. IPAF CLASFICATION CRITERIA
It wasn't until the 2015 ERS/ATS consensus paper that certain criteria were advocated.
The published IPAF criteria required:
1.Radiological or histopathological evidence of interstitial pneumonia
2.Complete clinical evaluation excluding other etiologies for interstitial
pneumonia
3.Incomplete features of a defined CTD
• To meet the criteria for IPAF, cases must fulfill the three a priori requirements, in
addition to a minimum of one element from at least two of the following domains

15. IPAF -classification Criteria…
A. Clinical domain (specific extra thoracic clinical features)
B. Serological domain (specific circulating autoantibodies)
C. Morphologic domain
 specific chest imaging features,
 histopathological features, or
 multi-compartment involvement
According to three published cohorts, there was a significantly higher prevalence of patients meeting serological and
clinical criteria.
Between 47 and 63% of IPAF patients had at least one clinical sign.
The most common clinical signs were the Raynaud phenomenon (28-39%), followed by the mechanic's hands (4-29%) and
Gottron sign (5 to 18%)

16. Clinical features

17. Serologic features

18. Serologic features…
• More than 90% of patients with IPAF have at least one of the serological criteria
• The main auto-antibody found in several series was positive high-titer ANA (48– 82%).
• Anti-SSa, antisynthetase antibodies,
• as well as high titer rheumatoid factor were also frequent

19. Morphologic features

20. Morphologic features …

21. Morphologic features…

23. Management
At present, it is unclear whether specific management distinct from that of IPF or CT-ILD
is needed
Facts regarding idiopathic(IPAF) treatment are merely limited to case series, and
 further research is necessary to determine the optimal treatment approach in the IPAF
population
As previously acknowledged with other ILDs
pulmonary rehabilitation
 long-term oxygen supplementation therapy if applicable, and
treatment of gastroesophageal reflux if existing is recommended

24. Management…
• no randomized controlled trials favoring immunomodulation in IPAF, and the
proposed treatment strategies are inferred from CTD-ILD studies
• In one study, patients with unclassifiable ILD, especially those meeting IPAF
criteria in the non-UIP pattern, intravenous pulse cyclophosphamide was suggested
to stabilize lung function.
• In that study, it was suggested that those with fibrosing predominant pathology,
might not benefit from corticosteroids and immunosuppressive drugs, as their
clinical behavior is more comparable to those with IPF.

25. Management…
• Another large retrospective study of 125 patients with CTD-ILD encompassed nineteen patients
with IPAF.
• In that study MMF was related to an improved FVC in all tested patients.
• The INBUILD trial suggests that nintedanib decreases the rate of ILD progression, as measured
by forced vital capacity (FVC) decline in patients who have a chronic fibrosing ILD and
progressive phenotype, irrespective of the underlying ILD diagnosis (including IPAF).
• Whether the combination of immunosuppressive therapy and antifibrotic drugs may be useful in
subjects with IPAF will need to be explored in the future.

27. • Currently, treatment decisions in patients classified as IPAF must be
based on careful evaluation of benefit:
• risk ratio in the individual subject and should ideally be discussed in
multidisciplinary setting. The demographic, clinical and autoimmune
features, as well as the imaging phenotype should be taken into
consideration.
• Eventually, the choice of firstline therapy may be based on the global
assessment of the patient (Figure 5).

29. CASE PRESENTATION
A 49-yr-old man was admitted to the
emergency department
 after the first wave of coronavirus in July
2020 because of
dyspnea, fever, and polyarticular morning
joint stiffness.
He is a farmer, and his medical history
includes type 1 diabetes and asthma.
• General examination revealed lung
crackles.

30. CASE PRESENTATION…
• His skin was normal (absence of rash, Gottron's sign, mechanic hands,
Raynaud's phenomenon, palmar telangiectasia), and he had no clinical
arthritis
• His T-was of 38.5°C with an spo2 95% to ambient air.
• Lab INVX a CRP- 31 mg/L,CBC-PROFILE NORMAL
• CPK level -normal

31. CASE PRESENTATION…
• HRCT-NSIP with OP patterns suspected of
SARS-CoV-2 infection, and the patient was
hospitalized in the COVID-19 ward .
• Later,RT-PCR testing for screening SARS-CoV-
2infection (three times on the BAL), bacterial
cultures, and screening HIV and hepatitis was all
found to be negative.
• amoxicillin/clavulanic acid was started and since
the patient needed oxygen supplementation, he
was transferred To ICU after a week of
hospitalization.

32. CASE PRESENTATION…
• An escalation therapy by piperacillin/tazobactam and doxycycline was
introduced
• with oxygen therapy of 8 L/min via a mask but intubation was never
required.
• BAL showed a lot of macrophages and a low CD4/CD8 ratio with
bacteriological and Pneumocystis Jiroveci research negative.
• ANA were positive with a 1:2640 titer and anti-RNP and anti-JO1 antibody
identification without complement consumption.

33. CASE PRESENTATION…
IPAF was established, and
treatment with corticosteroids 1 mg/kg/d of prednisone equivalent was started in the ICU.
• The patient was then transferred to the Internal Medicine Department for his management
• Where MMF was added about 12 days after corticosteroids, increasing dosage over 15 days up
to 2500 mg per day.
• Unfortunately, there was no improvement of his condition after 3 weeks with corticosteroids
• His need of oxygen did not decrease so that supplemental oxygen with 8L/min delivered via
nasal prongs was required for an SpO2 of 92% in a resting condition.
• He desaturated with exercises at SpO2 of 80%.

35. Case presentation
A previously healthy 22-year-old male
sugar cane farmer with no comorbid
illness presented with history of
progressive worsening breathlessness over
2 months duration.
Patient was apparently asymptomatic
before 2 months when he developed
breathlessness on exertion which
progressed to the degree to affect his
daily activities

36. Over 2 wks the breathlessness progressed and he was dyspnoeic even in bed
which aggravated on sitting up and improved on lying down.
• Patient was evaluated in a private setup where thoracic imaging by CT scan was suggestive of ILD
• treated with 30 mg oral steroids and discharged with advice for long-term oxygen therapy on home oxygen
support of 2 L/min
• Patient gave history of significant weight loss of around 10 kg in this period in spite of normal appetite and
absence of any gastrointestinal complaints
• patient was CHEST department, he was tachypneic at rest with a saturation of 78% on room air.
• On examination, he had significantly reduced chest expansion with bilateral fine basal crepitations.
• Other systemic examination was unremarkable

37. INVX-OFT-normal.
Further evaluation revealed that ANA positivity (1:160) and other autoimmune markers (anti-
dsDNA, anti-smith, anti-U1RNP, anticentromere) were negative.
Only anti-Ro52 antibody was strongly positive.
 Myopathic markers (creatine phosphokinase) and Schirmer’s test were within normal limits.
Chest X-ray showed reticular markings in bilateral lower zones. Echo normal.
He was not able to perform pulmonary function test (PFT) due to severe dyspnoea.
Amidst the hospital stay, we noticed that along with platypnea, he also had worsening hypoxemia
on sitting up as compared with the supine posture
after reviewing the literature, a diagnosis of POS was made

38. • A lung biopsy was not done as the
patient had significant hypoxemia at
rest and was unlikely to tolerate an
invasive procedure.
• Contrast enhanced CT showed ILD
with ‘probable’ UIP pattern .
• A diagnosis of rapidly progressive
interstitial pneumonia with
autoimmune features and POS was
made.

39. mgt
The patient was treated with
cyclophosphamide pulse (500 mg/m2) and
oral prednisolone (1 mg/kg/day).
A total of six pulses of cyclophosphamide
at intervals of 2 weeks were administered.
Azathioprine was added for
the maintenance of immunosuppression
and steroid was gradually tapered during
follow-up visits.

40. Outcome and follow-up
• After three cycles of cyclophosphamide the oxygen requirement of the patient has
been reduced to 2 L and after six cycles the patient required oxygen support only after exertion
(for 2 hours) .
• At 6 months follow-up, his pulmonary infiltrates improved together with improving
hypoxemia and resolution of platypnea/orthodeoxia.
• Initially, he was not able to do spirometry but after initiation of treatment he was able to
perform spirometry and diffusion capacity of lung for carbon monoxide (DLCO) manoeuvres.
Forced vital capacity improved from 1.2 L (45% of predicted) at 3 months to 1.9 L at 6 months
(71%) and DLCO improved from 10 mL/min/mm Hg (33% predicted) at 3 months to
15 mL/min/mm Hg (50% of predicted) at 6 months.

41. Prognosis
• Review of literature implies a better prognosis for patients with
idiopathic interstitial pneumonia with autoimmune features (IPAF) in
comparison to patients with IPF yet marginally worse than patients
with CTD-ILD.
• One study demonstrated an expressively inferior survival in those
meeting IPAF benchmarks when compared to a CTD-ILD patient and
barely slightly better survival compared to an IPF cohort

42. Complications
Idiopathic interstitial pneumonia with autoimmune features (IPAF) is a
progressive disease.
If not diagnosed or treated early it can progress to end-stage lung fibrosis.
Other complications include
Progressive lung fibrosis
Pulmonary hypertension
Cor pulmonale
Hypoxemic respiratory failure requiring domiciliary oxygen
Depression/anxiety

43. TAKE HOME MASSEGE
The diagnosis and management of idiopathic interstitial pneumonia with
autoimmune features (IPAF) need a multidisciplinary approach.
The following specialties can manage these patients through teamwork
• Radiologist
• Pulmonologist
• Pathologist
• Rheumatologist
• Thoracic surgery (i.e. for solid lung biopsy)

44. CASE PRESENTATION…
decided to start rituximab (Rtx) as salvage
therapy with two doses of 1 g at an interval of 15
days.
 After a few days, his need of oxygen decreased
and he was moved to a rehabilitation centre for
recovery 2 months after his admission with
oxygen needs of 3 L/min delivered via nasal
prongs.
At a 4-month follow-up,he no longer needed
oxygen and the HRCT control showed
significant improvement