Sandbox SSW

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sargun Singh Walia M.B.B.S.[2]

Overview

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [3]; Associate Editor(s)-in-Chief:

Overview

The clinical presentations of hypersensitivity pneumonitis depend on the frequency, length, exposure, and duration of illness. Due to a lot of variation in the the presentation hypersensitivity pneumonitis has been classified according to various schemes. Hypersensitivity pneumonitis may be classified into several subtypes based on various classifications methods such as classical classification, boyd classification, cormier classification, and selman classification.

Classification

• The clinical presentations of hypersensitivity pneumonitis depend on:
  • Frequency
  • Length
  • Exposure
  • Duration of illness
• Due to a lot of variation in the the presentation hypersensitivity pneumonitis has been classified according to various schemes.
• Hypersensitivity pneumonitis may be classified into several subtypes based on:
  • Classical classification:
    • Acute
      • Abrupt in onset.
      • Occurs after heavy exposure to antigen.
      • Symptoms can be confused with bacterial or viral infection.
      • On auscultation diffuse crackles and tachypnea are notable.
      • Histopathology reveals non-caseating interstitial granulomas with giant cells. 
    • Subacute
      • Gradual in onset.
      • Symptom like cough, fatigue, weightloss, and dyspnea may be seen.
      • Removal of exposure leads to complete resolution.
      • On auscultation diffuse crackles and tachypnea may be seen.
      • Histopathology reveals more well formed non-caseating interstitial granulomas and interstitial fibrosis.
    • Chronic
      • Insidious in onset with history of acute episodes.
      • Digital clubbing may be seen. 
      • Pulmonary fibrosis leads to disabling and irreversible respiratory symptoms.
  • Boyd classification:
    • Acute progressive
      • Severe symptoms occur after exposure to antigen.
      • Recurrent exposure leads to symptom progression.
      • Clinically patients are pyrexial with bilateral crackles on chest auscultation.
      • Patients may require hospitalization due to respiratory compromise.
    • Acute intermittent nonprogressive
      • Similar to acute progressive disease but less intense.
      • Patients feel well in between episodes.
      • Subsequent exposure leads to less severe symptoms.
      • Patients are clinically stable in the long run.
      • Pulmonary inflammatory response deteriorates with recurrent exposure to the antigen.
    • Chronic progressive disease
      • Occurs after recurrent acute episodes or insidiously.
      • Patients are diagnosed in the late stages.
      • Only clue for diagnosis is antigen exposure.
      • Patients often present with permanent disability in the form of pulmonary fibrosis or respiratory failure.
      • Disease is not reversed even after antigen exposure is avoided. 
    • Subclinical disease
      • Patients are immunological sensitized but are asymptomatic.
      • Patients with recurrent exposure to antigens may convert to chronic form.
  • Cormier classification:
    • Active
    • Residual
  • Selman classification:
    • Active non-progressive and intermittent
    • Acute progressive and intermittent
    • Chronic
      • Nonprogressive
      • Progressive

Prevalence

• sThe prevalence of hypersensitivity pneumonitis varies based on exposure/occupation.
• These are as following:
  • Farmers:
    • US: 8-540 cases per 100,000 persons per year among those at risk.
    • UK: 420-3000 cases per 100,000 persons per year among those at risk.
    • France: 4370 cases per 100,000 persons per year among those at risk.
    • Finland: 1400-1700 cases per 100,000 persons per year among those at risk.
  • Pigeon Breeders: 6000-21,000 cases per 100,000 persons per year
  • Bird Fanciers: 20-20,000 cases per 100,000 persons per year

Age

• Hypersensitivity pneumonitis usually affects patients in fourth to sixth decade of life.
• The mean age at diagnosis is 53 +/- 14 years.

Race

• There is no racial predilection to hypersensitivity pneumonitis.

Gender

• Hypersensitivity pneumonitis affects men and women equally.
• Death due to Hypersensitivity pneumonitis is reported more in men.

Pathophysiology of Oral Cancer

Tumor suppressor genes (TSGs)

• It is understood that oral cavity cancer is the result of allelic imbalance which is caused by chromosomal changes particularly in chromosome 3,9,11 and 17.
• These changes lead to mutation in tumor suppressor genes (TSGs).
• Mutation in the genes is one of the most common cause.
• Normally TSGs modulate normal growth.
• Mutation of these TSGs leads to dysfunctional growth control.
• Mutation most commonly occurs in either of the following:
  • Short arm of chromosome 3
  • TSG termed P16 on chromosome 9
  • TSG termed TP53 on chromosome 17
• Cytochrome P450 genotypes is related to mutations in some TSGs and lead to oral squamous cell carcinoma.
• In western countries (eg, United Kingdom, United States, Australia) TP53 mutations are the most common molecular change that leads to oral squamous cell carcinoma.

Oncogenes

• Cancer may also occur if there is mutation to other genes that control cell growth, mainly oncogenes.
• Oncogenes most commonly involved are:
  • Chromosome 11 (PRAD1)
  • Chromosome 17 (Harvey ras [H-ras])
• In eastern countries (eg, India, Southeast Asia), ras oncogenes is a more common cause of oral squamous cell carcinoma.

Carcinogen-metabolizing enzymes

• Carcinogen-metabolizing enzymes are known to cause cancer in some patients.
• Cytotoxic enzymes such as alcohol dehydrogenase result in the production of:
  • Free radicles
  • DNA hydroxylated bases
• These cytotoxic enzymes especially predispose oral squamous cell carcinoma.

Alcohol

• Alcohol dehydrogenase oxidizes ethanol to acetaldehyde which is cytotoxic in nature.
• cytochrome P450 IIEI (CYP2E1) also metabolizes ethanol to acetaldehyde.
• Alcohol dehydrogenase type 3 genotype predisposes to oral squamous cell carcinoma.
• Carcinogenic potential increases when combined with tobacco use.

Tobacco

• Cigarette smoke has various carcinogens which can lead to oral cancers.
• Low reactive free radicals in cigarette smoke interact with redox-active metals in saliva.
• This makes saliva to loose its antioxidant potential and become a potent pro-oxidant milieu.

Gross Pathological Findings

Images shown below are courtesy of Professor Peter Anderson DVM PhD and published with permission. © PEIR, University of Alabama at Birmingham, Department of Pathology