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A 57-year-old man comes to the office due to 2 months of progressive cough and weight loss.  He has a history of diabetes mellitus type 2 and chronic kidney disease.  He does not smoke cigarettes.  The patient traveled to Denmark 4 months ago for a 2-week vacation.  He has 2 cats and a bird.  He works in the maintenance department of a large hotel and services the hot tub and swimming pools.  Temperature is 38 C (100.4 F), blood pressure is 140/100 mm Hg, pulse is 88/min, and respirations are 16/min.  The patient is 190 cm (6 foot 3 inches) tall.  BMI is 22 kg/m2.  Examination shows cervical lymphadenopathy.  Chest imaging is shown in the exhibit.  Hemoglobin A1c is 8.5% and serum creatinine is 3.8 mg/dL.  Which of the following risk factors most likely contributed to this patient's current condition?

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Host factors that increase the risk of active tuberculosis

Immunosuppression

  • HIV
  • Glucocorticoid use
  • TNF-α inhibitors

Chronic diseases

  • Diabetes mellitus
  • Renal disease
  • Malignancy

Substance use
disorder

  • Illicit drug use
  • Alcohol use disorder
  • Tobacco use

Malnutrition

  • Underweight (BMI <18.5 kg/m2)
  • Vitamin D deficiency

TNF-α = tumor necrosis factor-alpha.

This patient's chronic cough, weight loss, cervical lymphadenopathy, and cavitary pulmonary lesion suggest active pulmonary tuberculosis (TB).  Exposure to Mycobacterium tuberculosis usually results in lifelong latent infection due to the formation of granulomas, which wall off the pathogen and limit spread.  However, the formation and maintenance of granulomas rely on coordination between monocytes and T lymphocytes.  Host conditions that weaken these aspects of immune function often significantly increase the risk of reactivation TB; these include the following:

  • Chronic kidney disease is associated with impaired function of monocytes and the cell-mediated immune response due to uremia and hypoalbuminemia.  Risk of TB is increased 6- to 50-fold in this population and is greatest in those with end-stage disease.
  • Poorly controlled diabetes mellitus is associated with immune impairment and alterations to cytokine signaling, which weaken the development and maintenance of granulomas.  Risk of TB is greatest in those with chronic hyperglycemia (eg, this patient with hemoglobin A1c of 8.5%).

Increased risk of reactivation TB is also seen in those with immunosuppression (eg, HIV, immunomodulatory/glucocorticoid medications), substance abuse, malnutrition, and advanced age.

(Choice A)  A tall body habitus is often seen in Marfan syndrome.  Although these individuals have an increased risk of spontaneous pneumothorax, manifestations would include acute shortness of breath and imaging evidence of air between the lung and chest wall.

(Choice B)  Patients who work with hot tubs and swimming pools can develop hypersensitivity pneumonitis due to inhalation of Mycobacterium avium, a nontuberculous mycobacterium.  Although most cases are marked by acute dyspnea, chronic symptoms can occur.  However, imaging would generally show patchy, ground-glass pulmonary infiltrates, not a cavitary lesion.

(Choice C)  Living with pets increases the risk of asthma due to increased exposure to allergens.  Asthma is typically marked by recurrent bronchoconstriction with acute periods of dyspnea, wheeze, and cough.  Chest x-ray may show hyperinflation and bronchial thickening but not cavitary infiltration.

(Choice D)  Travel to areas endemic for TB can increase risk of exposure and subsequent infection.  Endemic regions include India, sub-Saharan Africa, and Southeast Asia.  Denmark has a low incidence of TB; it is unlikely that the patient acquired the infection during his visit to this country.

Educational objective:
Mycobacterium tuberculosis infection is controlled by coordination between macrophages and T lymphocytes.  Conditions that impair immune function increase the risk of active tuberculosis; this includes chronic kidney disease, diabetes mellitus, HIV, substance abuse, malnutrition, and advanced age.