Is It Idiopathic Pulmonary Fibrosis or Not?

Mary Salvatore, MD; Genta Ishikawa, MD; Maria Padilla, MD


J Am Board Fam Med. 2018;31(1):151-162. 

In This Article

Mimicker No. 3: Stage 4 Sarcoidosis


Sarcoidosis is a multisystemic inflammatory disease of unknown etiology, characterized by the presence of noncaseating granulomas, and predominantly affecting lung. In the majority of patients, pulmonary sarcoidosis undergoes clinical remission either spontaneously or with therapy and favorable long-term outcomes are achieved. However, approximately 20% of patients develop pulmonary fibrosis (ie, radiographic stage iv sarcoidosis) with substantially increased mortality, therefore it can be another mimicker of UIP/IPF.[43,44] Stage 4 Sarcoidosis is a fibroticdisease with little or no granulomatous inflammation and clinical improvement is not expected with anti-inflammatory therapy.[45] Fibrosis in sarcoidosis originates from granuloma and along with bronchovascular bundles may result in bronchial distortion and large cystic changes, and interlobular septal fibrosis results in linear scarring.[46] The histologic features of UIP pattern (honeycombing, fibroblast foci, etc) are not typical in sarcoidosis. In sarcoidosis, wheezing, which is attributed to airway-centric fibrosis is common, although patients are less symptomatic than UIP/IPF.[47,48] In contrast with IPF, acute exacerbations of disease attributed to diffuse alveolar damage have not been reported in stage 4 sarcoidosis.[43]

Treatment is indicated in patients who are symptomatic, with progressively worsening pulmonary function.[44] Pulmonary fibrosis is an irreversible event, but in at least some patients, fibrosis coexists with active granulomatous inflammation. This is often difficult to discern and tests that suggest activity such as Gallium or Positron Emission Tomography (PET) scan are utilized to guide therapy. Treatments include multiple modalities aimed at suppressing inflammation with the use of anti-inflammatory agents (corticosteroids, methotrexate, azathioprine, leflunomide, mycophenolate mofetil, TNF antagonist, etc.). Although life expectancy is longer in S4 compared with UIP/IPF, once patients develop end-stage fibrotic lung disease, survival is limited and lung transplantation may be the treatment of last resort as it is for selected patients with pulmonary UIP/IPF.[43]


Stage 1 sarcoidosis demonstrates hilar and mediastinal lymphadenopathy, stage 2 sarcoidosis manifests as adenopathy and pulmonary nodules or densities in a peri-lymphatic distribution, stage 3 sarcoidosis has parenchymal involvement without lymphadenopathy, and stage 4 disease presents with fibrosis of the lung, which needs to be differentiated from UIP and CHP (Figure 7). Stage 4 sarcoid is an upper lobe–predominant fibrosis, which helps to differentiate it from UIP. In addition, it is not peripheral but instead is airway centered. Unlike CHP it tends to be posterior in the upper lobe and there is no air trapping.[49,50]

Figure 7.

Stage 4 sarcoidosis is an upper-lobe predominant fibrosis, which helps to differentiate it from usual interstitial pneumonitis (UIP). In addition, it is not peripheral but instead is airway centered.

Differentiation Pearl

  • Sarcoidosis has more in common radiographically with NSIP and CHP than with UIP because the fibrosis is not peripheral but instead follows the bronchovascular bundles.

  • Its upper-lobe predominance helps to differentiate S4 from NSIP.

  • A posterior predominance and absence of air trapping helps to differentiate S4 from CHP, which is upper lobe but more frequently anterior.