Marshall's syndrome is characterized by the appearance of a periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis in children. The condition cannot be recognized without adequate clinical suspicion. Findings from physical examination and exclusion of other conditions with a similar clinical presentation through laboratory workup are mandatory steps to make the diagnosis.
The principal signs and symptoms of Marshall's syndrome are the onset of a periodic fever (often > 39 °C) accompanied by pharyngitis, aphthous stomatitis, and cervical adenitis, which is why it is also termed PFAPA syndrome, named after its typical clinical features   . The onset of symptoms is usually before 5 years of age, but the disease was described in patients with aged between 3 months and 12 years . Their duration is approximately 3-6 days and recurrence is observed every 3-8 weeks    . In the asymptomatic period, children report no complaints, and normal growth and development are noted . In virtually all patients, Marshall's syndrome spontaneously resolves when adolescence is reached, and the disorder does not pose a risk for the child, especially with early recognition and initiation of proper glucocorticoid therapy . However, a very small number of individuals experience symptoms throughout adulthood and in fact, several reports show that an adult-onset form of the disease can develop as well    . Additional infrequently present symptoms of Marshall's syndrome are headaches, rash, joint pain, and gastrointestinal complaints, such as abdominal pain, dysphagia, weight loss and even anorexia   . Apart from a small predilection toward male gender, no other risk factors have been identified .
Although Marshall's or PFAPA syndrome is considered to be the most common cause of periodic fevers in childhood  , its diagnosis may be challenging in the absence of clinical suspicion, which is often lacking . For this reason, a detailed patient history and a meticulous physical examination are vital constituents during workup, as confirmation of this disorder relies almost exclusively on clinical criteria  . Appearance of fevers, their duration, as well as the duration of the asymptomatic period, should be noted during history taking, whereas observation of cervical lymphadenopathy, aphthous ulcers, and signs of pharyngitis in the absence of recurrent respiratory infections (which may point to infections or immunodeficiencies as the underlying cause) are diagnostic for Marshall's syndrome  . A complete blood count (CBC) and evaluation of basic inflammatory parameters may reveal leukocytosis, as well as elevated erythrocyte sedimentation rate (ESR) and C-reactive protein during symptomatic stages . Because of a very broad differential diagnosis (familial Mediterranean fever, hyperimmunoglobulinemia D syndrome, cyclic neutropenia, numerous infectious diseases, Behçet's disease, and juvenile rheumatoid arthritis), a complete biochemical and immunological workup is advised to rule out disorders with certain laboratory criteria  . Genetic studies are not yet available, as the etiology of Marshall's syndrome remains to be discovered, although various cells and cytokines in the immune system (Th1 subset of CD4+ T-lymphocytes, interleukin-1, and interferon), but also genes (primarily the Mediterranean fever gene, or MEFV) have been implicated in the pathogenesis .