Marshall Syndrome

Among the diseases that are characterized by seemingly unprovoked fever attacks, there is Marshall syndrome, manifested in children for several years (an average of 4.5 to 8 years).

The pathology described in The Journal of Pediatrics almost 30 years ago by four American pediatricians was named after the first co-author of the doctor of children's hospital in Philadelphia, Gary Marshall.

In English medical terminology, Marshall syndrome is called PFAPA syndrome, a periodic fever with aphthous stomatitis, pharyngitis and cervical lymphadenitis (adenitis), that is, inflammation of the lymph nodes in the neck.

[1], [2]

Epidemiology

The exact prevalence of this syndrome in the general population is unknown; boys Marshall syndrome are more common than girls (in 55-70% of cases).

The first manifestation is usually noted at the age of two to five years (approximately three and a half years), although it may be earlier. Manifestations of the syndrome (attack) in the majority of patients last for five to seven years and spontaneously terminate after reaching the age of ten or in adolescence.

Racial or ethnic features of the syndrome of research have not been identified; the number of family cases is insignificant.

[3], [4], [5], [6]

Causes of the marshall Syndrome

Suffice it for a long time periodically arising in children febrile fever with symptoms of inflammation in the throat, mouth and neck were considered idiopathic condition. Then the causes of Marshall's syndrome began to be associated with hereditary genetic mutations, but the specific gene was not finally determined. However, pediatricians take into account the family history and the propensity of blood relatives to inflammations of this localization and fever in the anamnesis: according to some data, a positive family history is revealed in 45-62% of patients. And in this predisposition, real risk factors for PFAPA syndrome are seen.

Known in modern clinical pediatrics, the genetic causes of Marshall syndrome lie in the uncharacteristic in infections of activation of both forms of the immune response - congenital and adaptive, as well as in changing the nature or kinetics of the immune response. Nevertheless, the pathogenesis of Marshall's syndrome is not fully understood until the end, since two versions are considered: the activation of immunity in recurrent infections and the violation of the mechanisms of the immune response. The first version is clearly untenable, as recent microbiological studies have shown conflicting serological results and a lack of response to antibiotic treatment.

And as for the problems with the mechanism of the immune reaction, there is a connection with defects in proteins of innate immunity. During each outbreak of this syndrome, the number of activated T cells or antibodies (immunoglobulins) in the blood does not increase, and the level of eosinophils and lymphocytes is often reduced. On the other hand, at the same time, activation of the production of interleukin IL-1β (which plays an important role in initiating fever and inflammation) and inflammatory cytokines (gamma interferon, tumor necrosis factor TNF-α, interleukins IL-6 and IL-18 ). And this may be the result of excessive expression of the genes CXCL9 and CXCL10 on the 4th chromosome.

The main mystery of the PFAPA syndrome is that the inflammatory reaction does not have infectious triggers, and the cause of gene expression is unknown. Officially Marshall syndrome is a disease of unknown etiology and uncertain pathogenesis (ICD-10 class 18 - not classified in other classes of symptoms and abnormalities, code - R50-R610). And if before he was referred to sporadic diseases, there are now grounds to consider it recurrent, that is, periodic.

[7], [8], [9], [10], [11]

Symptoms of the marshall Syndrome

The first signs of attacks in the Marshall syndrome - which, according to clinical observations, occur every 3-8 weeks - are in a sudden fever with peaks of fever to + 38.8-40.5 ° C and chills.

There may also be prodromal symptoms of Marshall syndrome, which occur about a day before the temperature increases in the form of general malaise and headache. Then there is inflammation of the mucosa in the mouth with small, painless aphthous ulcers (on average in 55% of patients). The pain in the throat (sometimes with exudation) has the form of pharyngitis - inflammation of the pharyngeal mucosa. There is a painful swelling of lymph nodes on the neck, as with lymphadenitis. It should be borne in mind that the whole complex of symptoms is observed in 43-48 %% of cases.

No other symptoms, such as rhinitis, cough, severe abdominal pain or diarrhea, do not occur with Marshall syndrome. Fever can last from three to four days to a week, after which the temperature also abruptly normalizes, and all manifestations disappear.

At the same time, children during periods between fever attacks are perfectly healthy and do not have any deviations in general development. According to clinical studies, the consequences and complications of PFAPA-syndrome are absent (or at the moment not identified).

Diagnostics of the marshall Syndrome

To date, the diagnosis of Marshall syndrome is based on a typical clinical picture. Analyzes are limited to the delivery of a general blood test.

To address parents' concerns, avoid unnecessary and expensive examinations and prevent potentially dangerous treatments, there are criteria for diagnosing PFAPA syndrome:

• presence of more than three fixed regular cases of fever lasting no more than five days, occurring at identical intervals of time;
• presence of pharyngitis with minor lymphadenopathy in the neck and / or aphthous ulcers on the oral mucosa;
• absence of developmental abnormalities and normal health between episodes of the disease;
• rapid resolution of symptoms after a single application of corticosteroids.

[12], [13], [14], [15], [16], [17]

Differential diagnosis

Differential diagnosis of this syndrome includes other diseases with periodic fevers: familial Mediterranean fever, autoimmune Behcet's disease, cyclic neutropenia (with a three-week cycle and extensive lesion of gum tissue), juvenile rheumatoid arthritis (Still's disease). It is necessary to exclude infections of the upper respiratory tract and caused by bacteria pharyngitis, tonsillitis, lymphadenitis, aphthous stomatitis.

It is important to differentiate between Marshall syndrome and congenital hyper-immunoglobulin D syndrome (mevalonate kinase deficiency syndrome) in children of the first year of life, in which periodic fever episodes-in addition to the symptoms inherent in PFAPA-are accompanied by abdominal pain, enlarged spleen, vomiting, diarrhea, pain and swelling of the joints; From a very young age, these children are delayed development and visual impairment.

Treatment of the marshall Syndrome

Pediatricians have not yet come to a consensus on what should be the treatment for Marshall syndrome.

The main drug therapy is symptomatic and consists of single doses of glucocorticoids. So, to facilitate fever, betamethasone or prednisolone is prescribed for Marshall syndrome. Prednisolone in tablets is taken orally immediately at the onset of fever - at the rate of 1-2 mg per kilogram of body weight of the child (maximum dose is 60 mg); Betamethasone 0.1-0.2 mg / kg.

Immunosuppressive effect of GCS is contraindicated in severe diabetes mellitus, hypercorticism, gastritis, kidney inflammation, post-vaccination, weakened children. The most common side effect of treatment with prednisolone is anxiety and sleep disturbance, so it should be taken several hours before bedtime. On the third or fourth day of the attack, the dose can be reduced to 0.3-0.5 mg / kg (once a day).

Clinical experience shows that antipyretic drugs, in particular non-steroidal anti-inflammatory drugs, help only to reduce fever, and in the fight against other symptoms are ineffective. With symptomatic treatment of this syndrome, it is important to assess the risks associated with possible side effects. So, before you use even a lozenge for sore throat, you should consult a doctor. In particular, it is recommended to choose those that do not contain antibiotics, since antibacterial agents do not give any result in Marshall's syndrome.

Children with Marshall syndrome need vitamins, especially calciferol (vitamin D), which - in addition to its role in calcium homeostasis and bone metabolism - can act as an immunoregulatory factor.

Prevention

Given the etiology of Marshall's syndrome, as well as the lack of an algorithm for its treatment, its prevention is not covered in domestic and foreign medical literature.

[18], [19], [20], [21], [22], [23],

Forecast

The prognosis of this pathological condition is considered favorable, as Marshall syndrome passes without consequences in the course of time.

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