PFAPA syndrome is a condition that typically presents in children with severe episodes of fever and certain accompanying symptoms. Because fever is a common symptom in pediatricians’ offices, the differential diagnosis is considered difficult. Exactly what triggers the febrile episodes in PFAPA syndrome in childhood remains unknown.
What is PFAPA syndrome?
The leading symptom of PFAPA syndrome is episodic, so-called recurrent fever in infancy. These episodes of fever, which recur at seemingly specific intervals, lead parents to visit a pediatric office along with the child. The pediatrician suspects the presence of a PFAPA syndrome, for example, if the parents can already name specific times for the next occurrence of an episode of fever during a seizure-free interval. Since febrile conditions often occur in the pediatrician’s office without any apparent reason from the history or other clinical symptoms, the differential diagnosis is quite difficult. Thus, numerous investigations are required in the sense of a diagnosis of exclusion so that the presence of PFAPA syndrome can be confirmed or not. Although the fever episodes with high fever up to 40 degrees Celsius can be very frightening for the parents, it is known that the PFAPA syndrome is benign, i.e. it is benign and also no late damage or late effects are to be expected. With advancing age, the fever episodes may disappear altogether and then do not recur later in life.
Causes
PFAPA syndrome is considered a rare pediatric disorder. Nevertheless, it must be assumed that a not insignificant percentage of affected children are not correctly diagnosed. This is due on the one hand to the unspecific febrile course of the disease, and on the other hand to the fact that the cause is still not clearly identifiable. PFAPA syndrome was first described in the USA in 1987 as a fever of unclear origin in children. According to current knowledge, the further physical and mental development and also the growth of the children is not affected by the occurrence of PFAPA syndrome. However, clear signs of inflammation and so-called autoantibodies can be found in the blood of affected children during fever episodes. Experts therefore now assume that PFAPA syndrome is an autoimmune disease. This would also explain the episodic fever. However, it is not known exactly against which endogenous structures autoantibodies are formed, which in turn then lead to the formation of immune complexes and thus to an inflammatory defense reaction of the body. In addition, genetic information plays a role in the development of disease. Today, it must be assumed that PFAPA syndrome is a genetically determined disorder of immune regulation.
Symptoms, complaints, and signs
The main symptom of the disorder is recurrent, relapsing fever, which occurs suddenly and in attacks. Early onset is also typical, usually in children who have not yet reached the age of five. The intervals between fever episodes are usually completely asymptomatic. Through further serial examinations, three leading symptoms, in addition to fever, of PFAPA syndrome have since been established. These include gingivitis, stomatitis, pharyngitis and associated swelling and inflammation of the cervical lymph nodes, lymphadenitis. In more than two-thirds of all patients with PFAPA syndrome, these three leading symptoms were present in addition to fever. Additional complaints and signs of the disease appear in the form of nonspecific abdominal and muscle pain, as well as skin rashes that can manifest all over the body. Children who show these skin symptoms in conjunction with the fever may be particularly likely to be misdiagnosed. In the acute fever episode, the typical signs of inflammation such as leukocyte proliferation, reactive left shift, and elevated blood cell sedimentation rate,ESR, can be regularly detected in laboratory blood tests.
Diagnosis and course of the disease
The tentative diagnosis is initially made on the basis of the leading clinical symptom of recurrent fever together with the various accompanying symptoms.Pharyngitis, stomatitis, and cervical lymphadenitis can be diagnosed by inspection and palpation. Laboratory tests are required to confirm the diagnosis. The classic course of the disease is that the episodes of fever occur at intervals of two to twelve weeks and last about five days each. Overall, the course of the disease is benign despite the dramatic nature, so that no late sequelae are to be expected. In addition, spontaneous remissions, i.e., the abrupt and permanent absence of symptoms, occur not infrequently after the age of 10.
Complications
Due to PFAPA syndrome, affected children primarily suffer from a very high fever. This fever occurs mainly in episodes and can significantly reduce the quality of life of the affected person. In many cases, there is also a delay in the development of the patient. Furthermore, PFAPA syndrome can also lead to discomfort in the teeth and inflammation of the gums. It is also not uncommon for those affected to suffer from inflammation of the throat and severely swollen lymph nodes. Pain in the abdomen or stomach can also become noticeable. Furthermore, the muscles hurt and the children suffer from rashes on the skin. The rashes may also cause inferiority complexes or lowered self-esteem in the children. In some cases, PFAPA syndrome also causes teasing or bullying. Direct treatment of this condition is usually not possible. However, with the help of medication, the episodes can be limited. No particular complications occur. However, it cannot be predicted whether PFAPA syndrome will have a negative effect on the life expectancy of the affected person.
When should you see a doctor?
The risk group for PFAPA syndrome includes children and infants. If fever breaks out repeatedly and intermittently in them, clarification of the symptoms should be made by a physician. Particularly high fever must be examined by a doctor. Life-threatening conditions can occur and there is a risk of secondary damage developing. Therefore, consultation with a physician is necessary. Spontaneous recovery often occurs, and in the further course of the disease, a new sudden spurt of fever may occur. To ensure that the child is well and adequately cared for during these phases, parents should seek comprehensive information from a physician. The disease characteristic of PFAPA syndrome is an abrupt onset of symptoms. There are no warning signs or indications beforehand that could be taken into consideration. In case of inflammation, discomfort in the mouth and throat, as well as changes in the appearance of the skin, the child needs medical help. If abdominal pain or muscular system disorders occur, the symptoms should be discussed with a physician. Swollen lymph glands or swelling of the neck indicate a health problem. If symptoms persist or increase in intensity, a physician is needed. Special care should be taken with rashes, open wounds or pus formation. If sterile wound care is not provided, blood poisoning may result. This presents a life-threatening condition that requires rapid action.
Treatment and therapy
Causal, i.e., cause-related therapy, has not been possible in PFAPA syndrome to date. All therapeutic attempts to prematurely interrupt the febrile episodes and accompanying symptoms are therefore symptomatic. In particular, it is seen in practice that the symptoms do not respond to the administration of antibiotics or nonsteroidal anti-inflammatory drugs. This also suggests that PFAPA syndrome is not caused by bacteria. However, the administration of cortisone, in particular the cortisone derivative prednisone, caused the fever episodes to disappear spectacularly within a very short time. This strengthened the suspicion that PFAPA syndrome is a special form of autoimmune disease. Therefore, high-dose cortisone administration as an infusion is considered the drug of choice.
Outlook and prognosis
PFAPA syndrome, which is common in children, represents an often unrecognized febrile illness. Most pediatricians do not recognize this condition. Regardless, the prognosis is not poor. The constantly recurring episodes of fever can persist for several years. They are treated symptomatically, and heal after a maximum of eight years. In rare cases, however, sufferers continue to struggle with the sequelae of PFAPA syndrome as adults.PFAPA syndrome occurs in episodes with symptoms that are often not recognized as related. There are episodes of fever, pharyngitis, tonsillitis, aphthae in the mouth, and swollen cervical lymph nodes. In children, such symptoms are not suspicious. PFAPA syndrome is usually misinterpreted as a cold sequelae or tonsillitis, and treated accordingly. Since the symptoms soon resolve, the true cause is not recognized. However, the same symptoms recur periodically over five to eight years. After a single administration of a corticosteroid at the onset of fever, the fever recedes. Likewise, the other symptoms disappear. The problem is that this only helpful therapy often has unpleasant consequences. Half of the patients treated in this way suffer an exacerbation of the symptoms of the disease for reasons that are still unknown. The more frequently corticosteroid therapy is used, the more likely the frequency of fever episodes increases. These now occur once or twice a week.
Prevention
Based on current knowledge, parents and physicians can do nothing to prevent the onset of the disease. To spare affected children an often years-long ordeal because of the fever episodes, PFAPA syndrome should be clearly diagnosed as early as possible.
Follow-up
In PFAPA syndrome, the measures of follow-up care are significantly limited in most cases because the exact cause of the disease is not yet known precisely. Therefore, parents should consult a physician with their children at a very early stage to prevent further complications and symptoms. The earlier a doctor is consulted, the better the further course of the disease. Most children are dependent on taking various medications. Care must be taken to ensure that the correct dosage is used in order to provide lasting relief from the symptoms. Parents, in particular, must properly monitor the intake of the medication. A doctor should be consulted immediately if there are any uncertainties or side effects. Regular check-ups by a doctor are also very useful in order to monitor the child’s condition permanently. The affected children should rest and take it easy. Effort should be refrained from in any case. As a rule, no further follow-up measures are necessary. With proper treatment, PFAPA syndrome does not usually reduce the patient’s life expectancy.
Here’s what you can do yourself
PFAPA syndrome initially requires treatment with medication. This can be supported by various self-help measures. In addition, the sufferer should drink plenty of fluids. Fluid intake replenishes the body’s mineral stores and prevents dehydration. Two to three liters per day are ideal, and mineral water, herbal teas and diluted fruit juices should be drunk. High fever can be reduced with the help of calf wraps. For this, two towels are dipped in cool water and wrapped around the calves after wringing them out briefly. These measures should be applied three times a day. In general, care should be taken that the fever does not rise to 39.5 degrees Celsius or higher. In case of high fever, the doctor should be informed. Home remedies are also not recommended for any accompanying symptoms such as headache or aching limbs. If PFAPA syndrome is present, do not exercise. The patient must completely cure the fever and get plenty of sleep during the illness phase. Stress must be avoided, as well as irregular sleep and consumption of stimulants. If the fever becomes more severe or is accompanied by unusual symptoms, the physician must be informed.
