A 19-year-old female came to the inpatient ward of the regional children’s hospital for an evaluation of hilar adenopathy.
Nine days prior to admission she developed a productive cough, rhinorrhea, shortness of breath and chest pain with deep inspiration.
She said she felt warm but had no fever. She also denied fever, chills, nausea, vomiting, recent skin changes or weight loss.
She was seen in the local emergency room on day 4 where screening labs showed elevated liver transaminases and an ultrasound of the liver and gallbladder were normal.
A chest radiograph showed widened mediastinum with hilar adenopathy. She was given azithromycin for bronchitis and sent to followup with her local physician which she did 5 days later.
At that time, she had an erythrocyte sedimentation rate of 100 mm/hour, and a C-reactive protein of 7.0 mg/dl. A tuberculin skin test with candidal control was placed at that time.
The past medical history was positive for erythema nodosum diagnosed and fully evaluated 3 months previously by a rheumatologist including a tuberculin skin test and chest radiograph that were negative. No obvious cause for the erythema nodosum was found.
She had no previous trauma, surgeries or significant illnesses and she had current immunizations.
The family history was negative for rheumatologic or immunological diseases. There was coronary artery disease and diabetes.
The social history showed she had a pet parrot for several years with no other animal contacts. She had lived in the Mississippi River area for the past 8 years.
There was no travel history, nor history of contact with persons living or working in a prison, homeless or in the military. The rest of the family and friends were healthy.
The review of systems was positive for some fatigue. She had no weight changes, night sweats, joint or skin problems.
The pertinent physical exam showed a teenager in no acute distress. She was afebrile, with normal respirations and growth parameters were at 90%; unchanged from outside records.
HEENT showed no obvious eye or other mucosal changes. Skin was normal. There were a few shotty anterior cervical lymph nodes that were < 0.5 centimeters.
She had no supraclavicular, axillary, epitrochlear, popliteal or groin nodes palpable. Heart, lungs, abdomen and musculoskeletal examinations were normal.
The working differential at that time was infectious (including coccidiomycosis, histoplasmosis, mycoplasma, pertussis, human immunodeficiency virus or other viral or bacterial etiology), immunological (including sarcoidosis or lupus), oncological (lymphoma) and other (Castleman’s syndrome).
The radiologic evaluation included a chest computed tomography examination which showed pretracheal and paratracheal, right hilar, and subcarinal mediastinal lymphadenopathy.
The work-up included consultations with pediatric pulmonary, rheumatology and oncology. An ophthalmological examination to look for evidence of lupus or other immunological diseases was negative.
The laboratory evaluation during her 2 day admission, her complete blood count, electrolytes, thyroid stimulating hormone, liver function tests, urinalysis, complement 4 level, ANCA (anti-neutrophil cytoplasmic antibodies), ANA (anti-nuclear antibody), and tuberculin skin test were negative.
A complement 3 level was slightly elevated and the control candidal intradermal skin test was positive. At the time of discharge the patient had almost complete resolution of her pulmonary symptoms and testing for coccidiomycosis, histoplasmosis, and blastomycosis were pending along with an ACE (angiotensin converting enzyme) and ENA (extractable nuclear antigens).
The working diagnosis at discharge was probably histoplasmosis, but possible sarcoidosis, that would be evaluated more when the pending testing was completed.
One week after discharge, the histoplasmosis antibody testing by immunodiffusion and complement fixation were positive but her urine antigen testing was negative. All other testing was negative.
The diagnosis of histoplasmosis was made and the results were communicated to her primary care physician who would followup with the patient
It was felt that her primary exposure occurred around the time she presented with erythema nodosum and the hilar adenopathy was now found incidentally on the chest radiograph.
Figure 58 – Three axial images from a chest CT performed with intravenous contrast demonstrate pretracheal and paratracheal (top), right hilar (middle) and subcarinal (bottom) mediastinal lymphadenopathy. There was also right middle lobe and lower lobe airspace disease and a small right pleural effusion (not shown). The findings were felt to be compatible with Mycobacterium tubercululi or Histoplasma capsulatum infection or sarcoidosis.
Histoplasmosis is caused by Histoplasma capsulatum and is endemic in the Mississippi, Ohio and Missouri River valleys and in the Southeast of the United States.
Infections usually occur sporadically but epidemics can occur when exposed to contaminated areas. Incubation is 1-3 weeks.
Primary infection usually is asymptomatic and diagnosed retrospectively because of pulmonary calcification and/or calcified hilar adenopathy noted later on an incidental chest radiograph.
If the patient receives a heavy load of the fungus they can have anorexia, chest pain, cough, fever, malaise and tachypnea.
Before calificiation, the hilar lymph nodes may only be enlarged prompting an evaluation for malignancy, tuberculosis and other causes.
Complications may include hemoptysis, mediastinal fibrosis, or pneumonia secondary to obstruction of the airways by the enlarged lymph nodes. Treatment is usually not necessary unless a complication arises.
In November 2008, an outbreak of histoplasmosis occurred among employees of the American Lung Association who had attended a meeting at the Governor’s mansion in Des Moines, Iowa.
Erythema nodosum is usually more often seen in adults than children. It usually presents as red warm plaques without epidermal changes on the lower extremities.
It is self limited, but because of pain may require nonsteroidal anti-inflammatory medications, steroids and/or iodine for treatment. Causes of it include:
- Streptococcus – one of the most common causes
- Lymphogranuloma venereum
- Mycobacterium tuberculi
- Yersinia enterocolitica
- Crohn’s disease
- Ulcerative colitis
- Behçet disease
- Castleman’s syndrome – benign giant lymph node hyperplasia
- Malignancy – Hodgkin and Non-Hodgkin lymphoma
- Medications – sulfonamides, halide, gold, oral contraceptives
Hilar adenopathy is not a common problem in the setting of a healthy child or teen, and therefore a prompt evaluation is necessary.
History is particularly important along with a careful physical examination as it helps to direct the workup.
Laboratory testing assists in confirming and denying possible diagnoses.
The differential diagnosis of hilar adenopathy includes:
- Mycobacterium tuberculi
- Systemic lupus erythematosus
- Castleman’s disease
- Chronic sinusitis
Questions for Further Discussion
1. What fungal diseases are common locally?
2. How does Bacille Calmette-Guérin (BCG) affect an intradermal tuberculin skin test?
To Learn More
To view pediatric review articles on this topic from the past year check PubMed.
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Rudolph CD, et.al. Rudolph’s Pediatrics. 21st edit. McGraw-Hill, New York, NY. 2003:1237, 1983.
American Academy of Pediatrics. Histoplasmosis, In Pickering LD, Baker CJ, Long SS, McMillan JA, eds. Red Book: 2006 Report of the Committee on Infectious Diseases. 27th edit. Elk Grove Village, IL: American Academy of Pediatrics; 2006;371-377.
Shaikh U, Blumberg DA. Lymphadenitis. eMedicine.
Available from the Internet at http://www.emedicine.com/ped/TOPIC32.HTM (rev. 5/18/2006, cited 2/7/08).
Hebel JL, Habid T. Erythema Nodosum. eMedicine.
Available from the Internet at http://www.emedicine.com/derm/TOPIC138.HTM (rev. 10/19/2006, cited 2/7/08).
Ley T. Health investigators link lung illness to Terrace Hill. Des Moines Register. January 29, 2008.
Available from the Internet at http://www.desmoinesregister.com/apps/pbcs.dll/article?AID=/20080129/NEWS/801290384/-1/archive (cited 2/7/08)
ACGME Competencies Highlighted by Case
1. When interacting with patients and their families, the health care professional communicates effectively and demonstrates caring and respectful behaviors.
2. Essential and accurate information about the patients’ is gathered.
3. Informed decisions about diagnostic and therapeutic interventions based on patient information and preferences, up-to-date scientific evidence, and clinical judgment is made.
4. Patient management plans are developed and carried out.
5. Patients and their families are counseled and educated.
7. All medical and invasive procedures considered essential for the area of practice are competently performed.
8. Health care services aimed at preventing health problems or maintaining health are provided.
9. Patient-focused care is provided by working with health care professionals, including those from other disciplines.
10. An investigatory and analytic thinking approach to the clinical situation is demonstrated.
11. Basic and clinically supportive sciences appropriate to their discipline are known and applied.
13. Information about other populations of patients, especially the larger population from which this patient is drawn, is obtained and used.
19. The health professional works effectively with others as a member or leader of a health care team or other professional group.
23. Differing types of medical practice and delivery systems including methods of controlling health care costs and allocating resources are known.
24. Cost-effective health care and resource allocation that does not compromise quality of care is practiced.
25. Quality patient care and assisting patients in dealing with system complexities is advocated.
26. Partnering with health care managers and health care providers to assess, coordinate, and improve health care and how these activities can affect system performance are known.
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa Children’s Hospital
April 7, 2008