The most common periodic fever syndrome in children is Periodic Fever, Aphthous stomatitis, Pharyngitis, and Adenitis (PFAPA). (1). This complication is characterized by the sudden onset of fever, aphthous stomatitis, pharyngitis, and cervical adenitis, as well as less common signs, such as headache, rash, and changes in the digestive system (2).
Marshall Syndrome or PFAPA was first described by Marshall in 1987, and it is mainly a disease of children under 5 years of age; however, it has recently been reported in adults. This disease manifests with periodical fevers of about 39°C at regular intervals (every 3 to 8 weeks) (3). The pathogenesis of PFAPA is unknown; nonetheless, genetic and immunological factors have been implicated in this regard (4). During PFAPA attacks, increased levels of activated T lymphocytes, GM-CSF, G-CSF, and pro-inflammatory cytokines, such as IL-1β, IL-6 and IL-8 have been observed (5).
The fever often increases to 39-40.5°C, which does not respond to antibiotics and antipyretics. Moreover, more than 90% of children have pharyngitis, followed by up to 75% of cervical adenitis and up to 50% of oral aphthosis during flares. Other symptoms that may present include headache, abdominal pain, arthritis, arthralgia, rash, and diarrhea(6).
PFAPA is diagnosed based on the mentioned criteria, and in addition to the modified Marshall's criteria, other criteria are also defined (4). Currently, the treatments used to improve its symptoms are corticosteroids, nonsteroidal anti-inflammatory drugs (NSAID), colchicine, cimetidine, and tonsillectomy with (ATE) or without (TE) adenoidectomy. The most commonly used first-line treatment in children with PFAPA syndrome is a low-dose corticosteroid, which can improve the symptoms of PFAPA syndrome in 95% of cases. Prednisone is typically given as a single dose of 1–2 mg/kg at the onset of a febrile episode (6)
The evidence indicates that probiotics, especially those containing lactobacilli and bifidobacteria, can be effective and helpful in reducing the occurrence and duration of coughs and colds in children and adults(7). The results of more than 20 studies show that probiotics have reduced the illness duration by about 30% (8).
According to the results of the studies, it is suggested to prescribe Lactocare and KidiLact to adults and children, respectively, to prevent respiratory infections, reduce the risk of other infections, and accelerate the treatment process of these diseases (9, 10). Probiotics can influence the gut microbiome while regulating the immune system. Furthermore, they are effective supplements for preventing or minimizing the immune system's involvement with pathogenic agents that enter the body through the digestive system and for cases, such as allergies or viral-respiratory infections, for which there are generally no specific treatments(6).
Probiotics can exert a protective role in the body; moreover, they prevent the connection of microbial and viral agents and their pathogenicity by fortifying mucosal membranes of the respiratory or digestive tracts and maintaining the integrity of the cells on the surface of these membranes. In addition, probiotics produce antimicrobial substances to destroy pathogens and reduce their number in the body(11).
When pathogenic agents come into contact with the cells of the digestive or respiratory tract wall, they trigger the body's acquired and innate immune systems. Accordingly, probiotics can modulate the immune system's response to these pathogenic agents and reduce their pathogenic and inflammatory effects by strengthening the immune system. Due to their anti-inflammatory effects, probiotics reduce the body's need to use corticosteroid anti-inflammatories, thereby mitigating and ceasing the inflammatory cycles caused by viral and bacterial diseases in the whole body (12).
Since only one study has been conducted so far to investigate the effectiveness of probiotics in preventing and treating this syndrome, this study aimed to evaluate the effect of probiotics on the prevention and treatment of this disease.