A holiday and a long haul flight. Managing the consequences.

A 26 year old woman travelled to Canada to visit family and take a hiking holiday. She stayed for 2 weeks. She travelled back to Pakistan on a non-stop flight. She carried a heavy carry-on bag into the aircraft, slept most of the way or watched a movie and had an uneventful flight. 10 days after arrival she experienced pain in the left chest on taking deep breaths. She had no fever, cough or significant breathlessness. She does not have night sweats and her appetite is good.When the pain got worse she decided to see a doctor 3 days later. She has a history of migraine but is currently not taking any medicine. She has had no significant illnesses in the past. She has no known drug allergies. She is married and is in a monogamous relationship. She is not aware of tuberculosis in her immediate circle of friend, colleagues and family. Her mother has rheumatoid arthritis and her father suffered from an acute MI which he survived and is now on aspirin and nitrates. She lives in a well to do neighbourhood in a large well aerated house. She is a financial analyst in a bank where her husband also works as an executive. They have no children.

What physical examination is required?

  • Make sure her vital signs are stable. Her BP is 120/70, respiration 16/min, pulse 78/min.
  • She is not breathless or orthopneic. No wheezing is audible without a stethoscope.
  • Check her legs and thighs for pain, swelling or tenderness. This is to make sure that she has or does not have deep vein thrombosis. On examination she has no evidence of DVT.
  • Her lymph nodes are not palpable superficially.
  • There is no edema.
  • Her chest moves equally on respiration. Breath sounds are reduced to absent in the lower chest at the back but are otherwise normal. There are no added sounds.
  • There is no evidence of a cardiac overload.
  • There is no ascites, visceromegaly or other abnormality in the abdomen.
  • The CNS is not affected.

Note that in the history and examination nothing irrelevant is mentioned yet all the required information is given. This is how to present a case on a ward round and also in the examination hall.

The doctor diagnoses pleurisy bilateral. What investigation should be done next?

  • An X ray chest. This showed fullness in the aortic pulmonary window and haziness in both lower areas of the chest.
  • Oxygen saturation. Her oxygen saturation while breathing room air was 98%.
  • D-dimer test.

Why the D-dimer test and not other imaging tests?

Given the patient’s history and findings on physical examination, the clinical probability of pulmonary embolism is not high. She has no symptoms or signs of deep venous thrombosis and has no known history of recent surgery, cancer, or venous thromboembolism.

For scenarios in which pulmonary embolism is unlikely, the d-dimer test, a high-sensitivity assay, is the best means for assessing patient risk. A normal d-dimer level effectively rules out the diagnosis of pulmonary embolism, whereas elevated levels of d-dimer necessitate additional diagnostic evaluation.

A Wells score could also be calculated to estimate the patient’s potential risk of pulmonary embolism. This patient has a Wells score of 1.5, which indicates a low probability of pulmonary embolism.

CTA of the chest, ventilation–perfusion scanning, ultrasonography of the legs, and transthoracic echocardiography would not be the first tests of choice in a patient for whom the risk of pulmonary embolism is low but has not been eliminated. These tests could be considered if the d-dimer level is elevated.

The patient’s D-dimer levels were significantly raised. A CTA was done.

CTA revealed no defects in pulmonary arterial filling that would indicate pulmonary embolism. The mediastinal windows show hilar and mediastinal lymphadenopathy in both lungs, findings that suggest the presence of a reactive process. The lung windows show diffuse ground-glass nodules, with trace pleural effusions.

d-dimer levels may be elevated in the absence of pulmonary embolism; causes include infectious, inflammatory, and malignant processes.

The patient now develops high grade fever with a white cell count of 7500 and and a normal platelet count. What could be the possible diagnosis?

The acute onset of isolated respiratory symptoms in the absence of pulmonary embolism suggests an infectious or inflammatory process. Although most cases of pneumonia are community acquired and are caused by bacterial infections that appear as lobar consolidations on chest imaging, mycobacterial infection, atypical bacterial or fungal pathogens can cause multifocal ground-glass nodules, mediastinal lymphadenopathy, and pleural effusions.

This patient’s country of origin should put tuberculosis on the top of the list. A more detailed history of exposures i.e. household help, recent visit to a patient with tuberculosis or a very crowded are where many people are coughing and spitting, may help to ascertain possible pathogens. Atypical noninfectious conditions, such as eosinophilic pneumonia, should also be considered but are less likely possibilities.

Sarcoidosis is a possibility as it is associated with pulmonary nodules and mediastinal lymphadenopathy in the absence of infection, although sarcoidosis is most often accompanied by extrapulmonary features in patients who present with acute illness. A more classic, acute presentation of sarcoidosis includes the triad of hilar lymphadenopathy, arthralgias, and erythema nodosum, known collectively as Löfgren’s. Sarcoidosis should be considered only after tuberculosis has been excluded.

She had no mycobacteria in induced sputum. Her Mantoux test was mildly positive but she had received BCG vaccine 3 days after birth. Her blood PCR for mycobacteria was negative.

On asking more about her recent activities she gave a history of spending a weekend with her cousin on a farm in rural Punjab. It was the month of July and the monsoons had set in while she was there. She had visited the chicken in the barn as producing eggs and chicken for cooking was a major activity on the farm. She had stayed for 2 days. The possibility of fungus in the hot humid environment is high.

Histoplasmosis is caused by the soil-dwelling fungus Histoplasma capsulatum. This fungus thrives in humid soil enriched with decaying bird droppings or bat guano or animal dropping which have not been removed regularly. H. capsulatum is endemic in many areas, including the Ohio and Mississippi River valleys, but it can be found throughout the world. This patient’s exposure to cow droppings, in combination with her clinical presentation, radiographic findings, and preliminary pathological findings, suggests the possibility of histoplasmosis. To confirm the diagnosis what should be done?

In this patient, in whom an acute infection with a high inoculum is suspected, the test that would be the most sensitive and specific for confirmation of the diagnosis of histoplasmosis is a mediastinal lymph-node biopsy. Although urinary testing for histoplasma antigen is not as sensitive as a tissue biopsy, it has the advantage of being noninvasive, and a positive result, when the pretest probability is high, would provide evidence of histoplasmosis that would be sufficient to initiate treatment.

Biopsy specimens of the right mediastinal and hilar lymph nodes were obtained by means of endobronchial ultrasound-guided fine-needle aspiration. Preliminary histologic analysis revealed a few yeast forms, which suggested the possibility of fungal infection.

Bronchoalveolar lavage was also performed, and samples were sent for bacterial and fungal acid-fast staining and culture.

Histopathological Analysis | A

Necrotizing granulomatous inflammation and a few yeast forms were observed that were consistent with a finding of histoplasmosis (see images). Staining for acid-fast bacilli and gram-positive species was negative, as were mucicarmine staining and Fontana–Masson staining for fungal organisms.

The patient was started on itraconazole and was discharged on hospital day 3. Her chest pain was managed with a short course of analgesics and resolved completely within 2 weeks, at which time she received follow-up care in the pulmonary clinic. Laboratory studies showed normal liver function and therapeutic levels of itraconazole. The patient completed a 12-week course of therapy without complications

  • In most instances, acute histoplasmosis is self-limiting in immunocompetent patients and requires no definitive antifungal therapy. Disseminated, chronic cavitary, and acute forms of the disease are treated with itraconazole when they are not life-threatening.
  • The treatment duration for acute histoplasmosis typically ranges 6 to 12 weeks, whereas at least 1 year of treatment is necessary in patients with disseminated or chronic cavitary disease.
  • Life-threatening illness necessitates treatment with intravenous amphotericin B, with subsequent transition to oral itraconazole after an initial response.

Published by


I am a Professor of Medicine and a Nephrologist. Having served in the Army Medical College, Pakistan Army for 27 years I eventually became the Dean and Principal of the Bahria University Medical and Dental College Karachi from where I retired in 2016. My passion is teaching and mentoring young doctors. I am associated with the College of Physicians and Surgeons Pakistan as a Fellow and an examiner. I find that many young doctors make mistakes because they do not understand how they should answer questions; basically they do not understand why a question is being asked. My aim is to help them process the information they acquire as part of their education to answer questions, pass examinations and to best take care of patients without supervision of a consultant. Read my blog, interact and ask questions so that I can help you more.

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Google photo

You are commenting using your Google account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s