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Reliable, easy-to-read patient information on common medical conditions — written in plain language, free of jargon, and grounded in current evidence. Browse the most frequent diagnoses, understand what they mean for everyday life, and learn which steps and questions help you have a focused conversation with your doctor.

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Hypersensitivity pneumonitis differential diagnosis

Introduction

Overview

Overview

The differential diagnosis of hypersensitivity pneumonitis is, primarily, a group of diseases known as idiopathic interstitial pneumonia. This group of diseases includes idiopathic pulmonary fibrosis (IPF) (which manifests histologically as usual interstitial pneumonia), idiopathic non-specific interstitial pneumonia (NSIP) and cryptogenic organizing pneumonia, among others. There are several important clinical syndromes that occur as a result of inhalation of organic agents but are not true forms of Hypersensitivity Pneumonitis.

Differential Diagnosis

Differential Diagnosis

  • HP occurs due to inhalation of organic agents .
  • Several diseases can occur due to this and mimic HP.
  • These disorders are as follows:
    • Inhalation fever:
      • Patients present with fever, chills, headache, and myalgias.
      • There are no pulmonary findings (although mild dyspnea may occur).[1]
      • Onset is 4-8 hours following exposure.
      • No long-term symptoms.
    • Organic dust toxic syndrome:
      • This syndrome occurs due to of exposure to bioaerosols contaminated with toxin-producing fungi (mycotoxins).[2][3][4]
      • Patients present with fever, chills, and myalgias 4-6 hours after exposure. [5]
      • In contrast to inhalation fever, the chest X ray may show diffuse opacities.
      • Bronchiolitis or diffuse alveolar damage may be present on lung biopsy specimens.
      • This is not a true form of HP because no prior sensitization is required.
    • Chronic bronchitis:
      • This is a very severe form of pulmonary disease.
      • Most common respiratory disorder among agricultural workers.
      • The prevalence of chronic bronchitis is much higher at 10%, compared with 1.4% for HP.
    • Exposure to aerosolized Mycobacterium avium complex (MAC):
      • Occurs due to exposure to aerosolized mycobacterium avium complex (MAC).
      • Hot tub lung is a term used to describe these hypersensitivity pneumonitis-like cases because they have generally been associated with hot tub use.
      • The syndrome has been linked to the high levels of infectious aerosols containing MAC organisms found in the water. Whether this syndrome represents a true MAC infection or classic HP remains controversial (Marras, 2005).

By frequency of Interstitial Lung Diseases (Xaubet, 2004):

  1. Idiopathic pulmonary fibrosis (38.6%)
  2. Sarcoidosis (14.9%)
  3. Cryptogenic organizing pneumonia (10.4%)
  4. Interstitial lung disease associated with collagen vascular diseases (9.9%)
  5. Hypersensitivity Pneumonitis (HP) (6.6%)
  6. Unclassified (5.1%)

In alphabetical order:

Restrictive lung disease must be differentiated from other diseases that cause dyspnea, cough, hemoptysis, and fever such as ARDS, bronchitis, hypersensitivity pneumonitis, pneumoconiosis.

Pulmonary Function Test Obstructive Lung Disease Restrictive Lung Disease
TLC ↑ ↓
RV ↑ ↓
FVC ↓ ↓
FEV1 ↓↓ ↓
FEV1/FVC ↓ N to ↑
MVV ↓ ↓

Approach to Lung Disorders

 
 
 
 
 
 
 
 
 
 
 
 
 
Spirometry
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Low FEV1/FVC ratio
 
 
 
 
 
 
 
 
 
 
 
 
 
Normal to high FEV1/FVC ratio
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Obstructive Lung Disease
 
 
 
 
 
 
 
 
 
 
 
 
 
Restrictive Lung Disease
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Bronchodilator therapy
 
 
 
 
 
 
 
 
 
 
 
 
 
DLCO
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Increased FEV1
 
 
 
 
 
 
 
No change in FEV1
 
 
 
Normal DLCO
 
 
 
 
 
 
 
Decreased DLCO
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Asthma
 
 
 
 
 
 
 
COPD
 
 
 
Chest wall disorders
 
 
 
 
 
 
 
Interstitial Lung Disease
 
 

Spirometry Findings in Various Lung Conditions

Spirometry showing Obstructive and Restrictive Lung Disease ([Source:By CNX OpenStax [CC BY 4.0 (http://creativecommons.org/licenses/by/4.0)], via Wikimedia Commons])
Disease Clinical manifestations Diagnosis
Symptoms Physical exam Lab findings Imaging Gold standard
Cough Dyspnea Hemoptysis Fever History/Exposure Cyanosis Clubbing JVD Peripheral edema Auscultation Other prominent findings CXR CT DLCco
Hypersensitivity Pneumonitis + + – + – + – –
  • Constitutional symptoms
  • Poorly defined micronodular or diffuse interstitial pattern
  • In chronic form
    • Fibrosis
    • Loss of lung volume
    • Coarse linear opacities
  • Ground-glass opacities or
  • Diffusely increased radiodensities
  • Diffuse micronodules
  • Focal air trapping
  • Mosaic perfusion
  • Occasionaly thin-walled cysts
  • Mild fibrotic changes 
 ↓
  • Clinical diagnosis
Acute Respiratory Distress Syndrome (ARDS) – + – – + – – –
  • Bilateral pulmonary infiltrates
    • Initially patchy peripheral
    • Later diffuse bilateral
  • Ground glass
  • Frank alveolar infiltrate
  • Bronchial dilatation within areas of ground-glass opacification
 ↓
  • PaO2 / FiO2 <300
Bronchitis Acute + – +/- + – – – – –
  • Diffuse wheezes
  • High-pitched continuous sounds
  • The use of accessory muscles 
  • Prolonged expiration
  • Rhonchi
  • Rales
  • N/A
  • Normal
  • N/A
 –
  • Clinical diagnosis
Chronic + + – –
  • A positive history of chronic productive cough 
  • Shortness of breath 
 + – + +
  • Prolonged expiration; wheezing
  • Diffusely decreased breath sound
  • Coarse crackles with inspiration
  • Coarse rhonchi
  • N/A
  • Radiolucency
  • Diaphragmatic flattening due to hyperinflation
  • Increased retrosternal airspace on the lateral radiograph
  • N/A
 ↓
  • N/A
Pneumoconiosis[6] SIlicosis[7][8] + + +/- –
  • Occupational history
    • Sandblasting
    • Bystanders
    • Quartzite miller
    • Tunnel workers
    • Silica flour workers
    • Workers in the scouring powder industry
 + + + –
  • Small round opacities
    • Symmetrically distributed
    • Upper-zone predominance
  • Diffuse interstitial pattern of fibrosis without the typical nodular opacities in chronic case
  • Nodular changes in lung parenchyma
  • Progressive massive fibrosis
  • Bullae, emphysema
  • Pleural, mediastinal, and hilar changes
 ↓
Asbestosis
  • Shipyard workers
  • Pipe fitting
  • Insulators
  • Predilection to lower lobes
  • Fine and coarse linear, peripheral, reticular opacities
  • Subpleural linear opacities seen parallel to the pleura
  • Basilar lung fibrosis
  • Peribronchiolar, intralobular, and interlobular septal fibrosis;
  • Honeycombing
  • Pleural plaques.
Berylliosis 
  • Electronic manufactures
 –
  • Hilar adenopathy
  • Increased interstitial markings.
  • Ground glass opacification
  • Parenchymal nodules
  • Septal lines
Byssinosis 
  • Cotton wool workers
  • Diffuse air-space consolidation
  • Pulmonary fibrosis with honeycombing
  • Peri bronchovascular distribution of nodules
  • Ground-glass attenuations
Sarcoidosis + + + + – – – –
  • Usually normal
  • Occasional crackles
  • Bilateral hilar lymphadenopathy
  • High-resolution CT (HRCT) scanning of the chest may identify
    • Active alveolitis
    • Fibrosis
 ↓
Pleural Effusion + + +/- +/- Transudate

Exudate

+/- +/- +/- +/-
  • Peripheral edema, distended neck veins, and S3 gallop suggest congestive heart failure.
  • Edema may also be a manifestation of nephrotic syndrome, pericardial disease, or, when combined with yellow nailbeds, the yellow nail syndrome.
  • Cutaneous changes and ascites suggest liver disease.
  • Lymphadenopathy or a palpable mass suggests malignancy.
 Supine
  • Blunting of the costophrenic angle
  • Homogenous increase in density spread over the lower lung fields

Lateral decubitus

  • Free flowing effusion as layers
  • Thickened pleura
  • Mild effusions can aslo be detected
 ↓
Interstitial (Nonidiopathic) Pulmonary Fibrosis + ++ + – + + + +
  • Increased A-a gradient
  • Elevated ESR
  • Serologic testing for ANA, RF, ANCA & ASCA may be positive
  •  Reticular and/or nodular opacities
  • Honeycomb appearance (late finding)
  • Bilateral reticular and nodular interstitial infiltrates
 ↓ Video-assisted thoracoscopic lung biopsy
Lymphocytic Interstitial Pneumonia[9] + + + + – + – –
  • Increased A-a gradient
  • Polyclonal hypergammaglobulinemia
  • Increased LDH
  • Bibasilar interstitial or micronodular infiltrates
  • Determines the degree of fibrosis
  • Cysts (characterstic)
 N Open lung biopsy
Obesity[10][11] + + – – – – – + –
  • X ray findings are often limited due to body habitus
  • CT findings are variable and depends upon severity of obesity
 N Clinical
Pulmonary Eosinophilia[12] + + + + Infections + – + +
  • Increased A-a gradient
  • Interstitial or diffuse nodular densities
  • Determines extent and distribution of the disease
  • Interstitial infiltrates
  • Cysts and nodules
 ↓ Biopsy of lesion (skin or lung)
Neuromuscular disease Scoliosis – + – –
  • Postural abnormality
 – – – –
  • In severe scoliosis, the rib cage may press against the lungs making it more difficult to breathe.
  • Accurate depiction of the true magnitude of the spinal deformity can be assessed by supine anteroposterior (AP) and lateral spinal radiographs
  • N/A
 N
  • Clinical
  • Radiographs
Muscular dystrophy – + – –
  • Proximal muscle weakness
 – – – –
  • N/A
  • N/A
 N
ALS – + – –
  • Muscle weakness
  • Neurological deficit
 – – – –
  • Symptoms begin with limb involvement diue to muscle weakness and atrophy. 
  • Cognitive or behavioral dysfunction
  • Sensory nerves and the autonomic nervous system are generally unaffected
 N/A Not significant/diagnostic Not significant/diagnostic –
  • Clinical diagnosis
  • Nerve conduction studies and needle electromyography (EMG) 
Myasthenia gravis – + – + H/O of difficulty getting up from chair – – – –
  • Extraocular, bulbar, or proximal limb muscles.
  • Breathing as rapid and shallow
  • Respiratory muscle weakness can lead to acute respiratory failure may require immediate intubation.
  • Anti–acetylcholine receptor (AChR) antibody (Ab) test +
  • Thymoma as an anterior mediastinal mass.
  • Thymoma as an anterior mediastinal mass.
 N
References

References

  1. ↑ Antonini JM, Lewis AB, Roberts JR, Whaley DA (April 2003). “Pulmonary effects of welding fumes: review of worker and experimental animal studies”. Am. J. Ind. Med. 43 (4): 350–60. doi:10.1002/ajim.10194. PMID 12645092.
  2. ↑ Lougheed MD, Roos JO, Waddell WR, Munt PW (November 1995). “Desquamative interstitial pneumonitis and diffuse alveolar damage in textile workers. Potential role of mycotoxins”. Chest. 108 (5): 1196–200. PMID 7587416.
  3. ↑ Jagielo PJ, Thorne PS, Watt JL, Frees KL, Quinn TJ, Schwartz DA (July 1996). “Grain dust and endotoxin inhalation challenges produce similar inflammatory responses in normal subjects”. Chest. 110 (1): 263–70. PMID 8681637.
  4. ↑ Emanuel DA, Wenzel FJ, Lawton BR (March 1975). “Pulmonary mycotoxicosis”. Chest. 67 (3): 293–7. PMID 46192.
  5. ↑ Malmberg P, Rask-Andersen A, Rosenhall L (April 1993). “Exposure to microorganisms associated with allergic alveolitis and febrile reactions to mold dust in farmers”. Chest. 103 (4): 1202–9. PMID 8131466.
  6. ↑ Gay SE, Kazerooni EA, Toews GB, Lynch JP, Gross BH, Cascade PN, Spizarny DL, Flint A, Schork MA, Whyte RI, Popovich J, Hyzy R, Martinez FJ (1998). “Idiopathic pulmonary fibrosis: predicting response to therapy and survival”. Am. J. Respir. Crit. Care Med. 157 (4 Pt 1): 1063–72. doi:10.1164/ajrccm.157.4.9703022. PMID 9563720.
  7. ↑ du Bois RM (2006). “Evolving concepts in the early and accurate diagnosis of idiopathic pulmonary fibrosis”. Clin. Chest Med. 27 (1 Suppl 1): S17–25, v–vi. doi:10.1016/j.ccm.2005.08.001. PMID 16545629.
  8. ↑ Neghab M, Mohraz MH, Hassanzadeh J (2011). “Symptoms of respiratory disease and lung functional impairment associated with occupational inhalation exposure to carbon black dust”. J Occup Health. 53 (6): 432–8. PMID 21996929.
  9. ↑ Honda O, Johkoh T, Ichikado K, Tomiyama N, Maeda M, Mihara N, Higashi M, Hamada S, Naito H, Yamamoto S, Nakamura H (1999). “Differential diagnosis of lymphocytic interstitial pneumonia and malignant lymphoma on high-resolution CT”. AJR Am J Roentgenol. 173 (1): 71–4. doi:10.2214/ajr.173.1.10397102. PMID 10397102.
  10. ↑ Zammit C, Liddicoat H, Moonsie I, Makker H (2010). “Obesity and respiratory diseases”. Int J Gen Med. 3: 335–43. doi:10.2147/IJGM.S11926. PMC 2990395. PMID 21116339.
  11. ↑ O’Neill, Donal (2015). “Measuring obesity in the absence of a gold standard”. Economics & Human Biology. 17: 116–128. doi:10.1016/j.ehb.2015.02.002. ISSN 1570-677X.
  12. ↑ de Górgolas M, Casado V, Renedo G, Alen JF, Fernández Guerrero ML (2009). “Nodular lung schistosomiais lesions after chemotherapy for dysgerminoma”. Am. J. Trop. Med. Hyg. 81 (3): 424–7. PMID 19706907.


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