What is in the Differential Diagnosis of Fatigue?

Patient Presentation
A 14-year-old male came to clinic for advice about seasonal allergic rhinitis. It usually was controlled with daily cetirizine but he was having more rhinorrhea, sneezing and some coughing and his mother complained that he always seemed very tired. He had some itchy eyes but denied pain or fever. The cough was non-productive but he said he would cough up clear mucous that was just like his rhinorrhea. He had just started high school where he was taking advanced courses and was in several extracurricular activities. Over the summer he had been active but had not been training before also starting running with the cross-country running team. He said that he tried to go to bed at a consistent time, but that he was only getting around 7 hours of sleep a night. He was eating a fairly good diet. He denied feeling overwhelmed and loved his classes and activities. The past medical history showed mild intermittent asthma and seasonal allergic rhinitis.

The pertinent physical exam showed a generally well-appearing male with normal vital signs. He had a 1-pound weight gain since his well adolescent visit a month previously. He had mild tearing and allergic shiners by his eyes. His nose had boggy membranes with copious clear/white rhinorrhea that was also seen in the posterior pharynx. His lungs were clear. His skin was not dry nor had any rashes. The diagnosis of seasonal allergic rhinitis and fatigue due to multiple reasons was made. The physician recommended to increase the amount of cetirizine and also beginning a nasal steroid. “You should also keep your albuterol inhaler with you and if you have more coughing, you should try it. The cough may be because of your asthma, especially if it gets worse when you are exercising. I also want you to call me, if these medicines aren’t helping in 5-7 days. I have some other medicines which may help,” she offered. The physician also discussed with the adolescent ways he could prioritize consistent sleep in his schedule. “Taking your medicine, good sleep, good eating and drinking lots of fluids, and some healthy exercise usually improves your energy,” she said.

Fatigue is a subjective feeling of decreased energy, tiredness or feeling of exhaustion. Lethargy is often used synonymously, but lethargy is a state of being drowsiness or sleepy, and implies mental status changes. Both can cause the person to be apathetic or less active.

Fatigue is a common state that almost everyone experiences multiple times in his or her lifetime. For most people it is a relatively acute or short-term chronic problem, often with a relatively easily identifiable problem cause, such as inadequate sleep, acute illness, or overexertion. For some, it can be less readily identifiable such as depression, anemia, or hypothyroidism or because of a chronic illness with its waxing and waning natural history or being under- or over-treated. Chronic fatigue and cause decreased quality of life, school or work problems, and depression.

It seems to many health care providers that adolescents and their parents complain about fatigue. This is not surprising as adolescents often do not get enough sleep, may be either overexerting themselves with activities or conversely be deconditioned because of little activity, be worried about school and other life issues, or not eat or drink consistently or are dieting. They may also be taking medications or drugs, have a chronic disease or are pregnant.

The keys to the evaluation of fatigue often lie in a detailed history and review of systems that can then guide laboratory evaluation and treatment. Laboratory testing can include a complete blood count, complete metabolic panel, thyroid function testing, erythrocyte sedimentation rate, and urinalysis. Other simple tests to consider include pregnancy test, Epstein Barr titers or monospot, rheumatoid factor, tuberculosis testing, and chest radiograph. Many other tests can also be ordered based on history and previous testing.

Other PediatricEducation.org cases of interest:

  • Health problems caused by inadequate sleep, found here.
  • Obesity, activity, and weight loss, found here and here.
  • Growth and pubertal development, found here.

Learning Point
The differential diagnosis of fatigue is enormous. Below are only some of the potential causes given as a framework when considering the individual patient’s story.

  • Overexertion
  • Deconditioning
  • Puberty
  • Sleep
    • Insufficient/deficit
    • Sleep disorders
      • Insomnia
      • Narcolepsy
      • Obstructive sleep apnea
  • Psychological/psychiatric
    • Boredom
    • Depression
    • Anxiety/stress/insecurity – worrier, bullying, self-esteem issues
    • School phobia
    • Normal quiet personality
  • Infections
    • Obvious – upper respiratory infection, streptococcal pharyngitis, pneumonia, gastroenteritis, etc..
    • Surreptitious – urinary tract infection, abscess, osteomyelitis, HIV, tuberculosis, parasites
    • Acute viral illnesses
      • Adenovirus
      • Epstein-Barr virus
      • Influenza
      • Lyme disease
      • Parvovirus
  • Medications and illicit drugs
    • Alcohol
    • Antidepressants
    • Antihistamines
  • Metabolic
    • Anemia
    • Abnormal diet or malnutrition
    • Hypoglycemia
    • Hyperammonemia
  • Obesity
  • Pregnancy
  • Chronic illnesses
    • Cardiovascular
      • Congenital heart disease
      • Acquired heart disease, e.g. endocarditis
    • Endocrine
      • Diabetes
      • Hypothyroidism
      • Hyperthyroidism
      • Addison disease
      • Cushing’s syndrome
    • Gastrointestinal
      • Crohn’s disease
      • Ulcerative colitis
      • Hepatitis or liver failure
    • Renal – renal insult or failure
    • Neurological/Genetic
      • Myasthenia gravis
      • Muscle weakness
      • Many other neurological or genetic problems
    • Miscellaneous
      • Chronic fatigue syndrome
      • Heavy metal intoxication
      • Pain, e.g. Fibromyalgia
    • Oncologic – malignancy
    • Respiratory
      • Allergies
      • Asthma – unrecognized or uncontrolled
      • Cystic fibrosis
    • Rheumatologic
      • Juvenile idiopathic arthritis
      • Dermatomyositis
      • Systemic lupus erythematosus

Questions for Further Discussion
1. How much cetirizine can be used for seasonal allergic rhinitis? To learn more click, here.
2. What is the definition of chronic fatigue syndrome?
3. What are indications for referral for a sleep study or sleep medicine specialist?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for this topic: Fatigue.

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Illingworth RS. Common Symptoms of Disease in Children. Blackwell Scientific Publications: Oxford. 1988:42-45.

Fisher M. Fatigue in adolescents. J Pediatr Adolesc Gynecol. 2013 Oct;26(5):252-6.

Crichton A, Knight S, Oakley E, Babl FE, Anderson V. Fatigue in child chronic health conditions: a systematic review of assessment instruments. Pediatrics. 2015 Apr;135(4):e1015-31.

Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa Children’s Hospital