Fatigue is a symptom defined by a subjective sense of increased more than average tiredness and exhaustion after a routine task that impairs one’s physical and mental capabilities^[1]. The chronic fatigue syndrome is defined as severe persistent debilitating fatigue for six months or more along with somatic symptoms like myalgia, headache, joint pain and sore throat^[2]. The incidence of fatigue is high in children particularly in adolescence due to high education and psychosocial stress^[3]. It can have severe debilating adverse effects on children and negatively impact their academic and social life.The fatigue can also be a symptom of an underlying disease. Hence, a thorough clinical evaluation and relevant investigations should be performed to rule out any underlying pathology.

• There is no known classification of fatigue in children.

• The pathogenesis of fatigue in children is unknown and it depends upon the underlying disease.
• It is characterized by impaired humoral and cellular immunity with a reduced response by natural killer cells and lymphocytes in response to various viral infections^[4].
• A reduced level of the total immunoglobulins G and its various subclasses have also been documented.

Fatigue may be caused by

• Anemia
• Congestive heart failure^[5]
• Cancer^[6]
• Cardiac septal defect
• Diabetes
• Obesity
• Cushing’s syndrome^[5]
• Inflammatory bowel disease^[1]
• Multiple sclerosis^[7]
• Reduced physical fitness
• Anxiety ^[8]
• Fibromyalgia
• Juvenile rheumatoid arthritis
• Intussusception
• Depression^[8]
• Obstructive sleep apnea
• Cystic fibrosis
• Strained family relations

Chronic fatigue in children should be differentiated from other symptoms that result in extreme tiredness like sleeplessness and muscle weakness^[5]. These symptoms can be differentiated by thorough examination of the patient. The symptoms of tiredness due to sleeplessness are alleviated by adequate sleep and adjusting sleep wake cycle^[9]. The muscle weakness is mainly due to underlying pathogy at the neuromuscular junction. It is tested by detailed neurological examination assessing muscle motor strength testing^[5].

The prevalence of fatigue in children is approximately 59,000 to 386,000 per 100,000 individuals in terminal cancer.

• The prevalence of fatigue increases with age. The fatigue commonly affects children during childhood, school, and adolescent years^[10].
• The peak age of prevalence is 15 years. The prevalence than decreases exponentially in boys while it remains high in girls till 18 years of age^[10]..

Girls are more commonly affected by fatigue than boys. The female to male ratio is approximately 1.3 to 1.^[3]

There is no racial predilection for fatigue in children.

• Common risk factors in the development of fatigue in children are family history of fatigue, known history of asthma, mood disorder like anxiety, depression, patient belonging to upper-middle class socioeconomic group^[11][12][13].

• Early clinical features include headache, myalgia, joint pain, increased body temperature, more tiredness thn normal after doing physical exertion^[14].
• If left untreated, 20.5% of patients with fatigue in children may progress to develop depression, mood disorders, increase absence from school, and poor academic performance^[15].
• Prognosis is generally good with the resolution of symptoms in 46.6% of patients after four to six months^[13].

• The diagnosis of chronic fatigue syndrome is based on the Centers for Disease Control and Prevention criteria^[2].
• The diagnosis of chronic fatigue syndrome is made when at least four of the following eight diagnostic criteria are met and symptoms are present for more than 6 months:

• Impaired memory or concentration
• Sore throat
• Painful cervical or axillary lymph nodes
• Myalgia
• Polyarthralgia
• New onset of headache
• Unrefreshing sleep
• Malaise after exertion

• Any underlying medical or psychiatric illness has been ruled out.

• Symptoms of fatigue may include the following^[2]:

• Extreme tiredness more than normal for more than one month.
• Onset of fatigue along with exacerbating factors should be inquired.
• A detailed medical and psychiatric history should be asked to look for underlying disease or psychiatric illness.
• Systematic symptoms like breathlessness, new-onset headache, muscle aches, and joint pains.
• Substance abuse, alcohol or use of over-the-counter medications should be asked particularly from adolescent and teenager patients.

• Physical examination may be remarkable for^[2]:

• Conjunctival pallor in anemia
• Petechia and purpura in leukemia patients
• A thorough examination to rule out psychiatric or neurologic disease
• Tenderness in multiple joints and muscle in fibromyalgia and juvenile idiopathic arthritis
• Tenderness in the cervical or axillary lymph nodes

• Laboratory findings consistent with the diagnosis of fatigue in children due to underlying diseases include^[2]:

• Complete blood count with differential leukocyte count (to rule out anemia or leukemia)
• Erythrocyte sedimentation rate to rule out inflammatory disease.
• Alanine transaminase, aspartate transaminase, total albumin, globulin level and total protein levels to assess liver function.
• urine analysis, serum creatinine, blood urea nitrogen, serum calcium, phosphate and electrolytes to look for underlying renal disease.
• Serum Thyroid-stimulating hormone level to rule out thyroid disease.
• Fasting blood glucose levels to rule out diabetes.
• Specific neuroimaging and viral serologies like HBV, HCV, EBV should be done in patients with particular risk factors.

There are no ECG findings associated with fatigue in children.

There are no x-ray findings associated with fatigue in children.

There are no echocardiography/ultrasound findings associated with fatigue in children.

There are no CT scan findings associated with fatigue in children.

There are no MRI findings associated with fatigue in children.

There are no other imaging findings associated with fatigue in children.

• Fatigue in children may also be diagnosed using various modular instruments^{[16][17][18][19][20]}:

• Pediatric Quality of Life Inventory (PedsQL)
• Multidimensional Fatigue Scale (MFS)
• Fatigue Scale-Child [FS-C]
• Fatigue Scale-Adolescent [FS-A]

• There is no proven treatment for fatigue in children; the mainstay of therapy is supportive care.
• Cognitive-behavioral therapy and graded exercise therapy do not have proven efficacy for the treatment of fatigue in children. Several randomized controlled trials have shown benefit in the symptoms of fatigue^[21]. Graded exercise therapy particularly aerobic exercises have shown improvement in depression and energy levels in adolescent patients with chronic fatigue syndrome^[22].
• Children with chronic fatigue have disrupted sleep with daytime drowsiness resulting in disturbed cortisol levels. Patients should be advised on activity management and behavioral modification with regular sleep patterns avoiding prolonged sleep hours and daytime naps. Regular sleep pattern will improve diurnal cortisol levels ^[23].
• The patients complaining of pain should be referred to specialized pain clinics and adequate treatment should be administered. Amitriptyline is administered in gradually increased doses for the management of pain with low doses given initially. The physicians should avoid prescribing opiates due to the high incidence of adverse reactions^[21].
• Impaired cognition in patients can be improved with strategies implemented to improve attention span in children. These include a conducive school environment to improve the child’s attention, frequent revisions, reducing the amount of new information a child learns in a day, and use of visual tools in learning^[24][25].
• Dizziness and headache should be treated by increasing physical activity, increase fluid intake with average of 2-3 liters per day, and high consumption of salt in some cases^[24].

• There is no known surgery for treatment of fatigue in children.

• There are no primary preventive measures available for fatigue.