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 .
Entire Body System
- Short Stature
Those with Marshall syndrome can also have short stature. Some researchers have argued that Marshall syndrome represents a variant form of Stickler syndrome; but this remains controversial. [diseaseinfosearch.org]
Symptoms - Marshall syndrome * Short stature * Short nose * Depressed nose * Flat nasal bridge * Anteverted nose Causes - Marshall syndrome Not supplied. Prevention - Marshall syndrome Not supplied. [checkorphan.org]
Physical findings: People with MSS may present with: • Short stature; • Kyphoscoliosis; • Nontraumatic fractures; • Failure to thrive; • Developmental delay or intellectual disability; • Respiratory compromise; • Unusual facies with wide and prominent [secure.ssa.gov]
stature, and intellectual disabilities) 759.89 Rud's (mental deficiency, epilepsy, and infantilism) 759.89 Russell (-Silver) (congenital hemihypertrophy and short stature) 759.89 Seckel's 759.89 sick Silver's (congenital hemihypertrophy and short stature [icd9data.com]
Those with Marshall syndrome can also have short stature. [rarediseases.info.nih.gov]
- Multiple Congenital Anomalies
Syndrome of accelerated skeletal maturation in infancy, peculiar facies, and multiple congenital anomalies. [ncbi.nlm.nih.gov]
- Recurrent Respiratory Infections
infections (which may point to infections or immunodeficiencies as the underlying cause) are diagnostic for Marshall's syndrome. [symptoma.com]
- Weight Loss
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. [symptoma.com]
Jaw & Teeth
- Aphthous Stomatitis
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. [symptoma.com]
[…] and lasting for 3-6 days, cervical adenitis, pharyngitis and aphthous stomatitis. [clujulmedical.umfcluj.ro]
“Syndrome of Periodic Fever, Aphthous stomatitis, Pharyngitis, and Adenitis (PFAPA) what it isn’t. What is it? J Pediatr. 1999;135(1):1–5. [ped-rheum.biomedcentral.com]
- Decreased Sweating
[…] ability to sweat Decreased sweating Sweating, decreased [ more ] 0000966 Hypoplasia of the maxilla Decreased size of maxilla Decreased size of upper jaw Maxillary deficiency Maxillary retrusion Small maxilla Small upper jaw Small upper jaw bones Upper [rarediseases.info.nih.gov]
- Hearing Impairment
Overview A rare genetic disorder characterized by a distinctive face and vision and hearing impairment. [checkorphan.org]
Hearing impairment in Stickler syndrome: a systematic review. Orphanet J Rare Dis. 2012 Oct 30;7:84. doi: 10.1186/1750-1172-7-84. Review. Acke FR, Dhooge IJ, Malfait F, De Leenheer EM. Hearing impairment in Stickler syndrome: a systematic review. [ghr.nlm.nih.gov]
impairment 0000407 Short nose Decreased length of nose Shortened nose [ more ] 0003196 Short stature Decreased body height Small stature [ more ] 0004322 Thick lower lip vermilion Increased volume of lower lip Plump lower lip Prominent lower lip [ more [rarediseases.info.nih.gov]
Face, Head & Neck
- Cerebral Calcification
[…] breadth of nasal bridge Increased width of bridge of nose Increased width of nasal bridge Nasal bridge broad Wide bridge of nose Widened nasal bridge [ more ] 0000431 30%-79% of people have these symptoms Amblyopia Lazy eye Wandering eye [ more ] 0000646 Cerebral [rarediseases.info.nih.gov]
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 .
Treatment - Marshall syndrome Due to complicated medical treatment of symptoms (sometimes in parallel involving several Marshall syndrome cannot be cured; however, the symptoms caused by the disease should be treated. [checkorphan.org]
The etiology remains unknown and there is no definitive treatment. [ncbi.nlm.nih.gov]
Treatment Treatment Options: No treatment is available for this disorder beyond cataract removal. Patients need to be monitored for retinal breaks and detachments. [disorders.eyes.arizona.edu]
CLOSE Medical Disclaimer The medical information on this site is provided as an information resource only, and is not to be used or relied on for any diagnostic or treatment purposes. [diseaseinfosearch.org]
TREATMENT There is no cure for MSS. Treatment is symptom specific and supportive. Children with MSS are treated with aggressive management of early respiratory and feeding difficulties. [secure.ssa.gov]
[…] failure to thrive skeletal accelerated skeletal maturation craniofacial dysmorphic facial features prominent eyes bluish sclerae coarse eyebrows upturned nose mental retardation respiratory difficulties Genetics most cases are sporadic Treatment and prognosis [radiopaedia.org]
Prognosis - Marshall syndrome As they age, vision and hearing problems will generally worsen for patients with Marshall syndrome. [checkorphan.org]
The prognosis is excellent, with a progressive decrease in the incidence of periodic fever and an absence of complications. However, the etiology of Marshall's syndrome has not yet been determined. [em-consulte.com]
Prognosis has improved considerably in recent years to nearly full life expectancy. However, if left untreated, it can be life threatening. [tall.life]
Prognosis Marshall-Smith syndrome has long been considered a childhood condition because affected individuals did not typically survive past childhood.. [marshallsmith.org]
The etiology remains unknown and there is no definitive treatment. [ncbi.nlm.nih.gov]
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 [symptoma.com]
It is hoped that the etiology of the syndrome will be discovered as more cases are recognized and reported by pediatricians caring for infants with failure to thrive, advanced bone age, and chronic respiratory symptomatology. [pediatrics.aappublications.org]
However, the etiology of Marshall's syndrome has not yet been determined. Mots clés : periodic fever ; Marshall's syndrome ; PFAPA syndrome. © 2000 Éditions scientifiques et médicales Elsevier SAS. Publié par Elsevier Masson SAS. [em-consulte.com]
[…] arterial tortuosity syndrome and X-linked cutis laxa. ,  The acquired form is divided into two groups according to the clinical and histological features: Type 1 or generalized acquired elastolysis and type 2 or Marshall's syndrome.  A number of etiologic [ijdvl.com]
A recent review suggests “Epidemiological evidence indicates a significant association between vitamin D deficiency and an increased incidence of several autoimmune diseases (4).” [sciencebasedmedicine.org]
Accident Analysis & Prevention (Candrive special issue) 2013;61:236-244. [med.uottawa.ca]
Prevention - Marshall syndrome Not supplied. Diagnosis - Marshall syndrome Individuals are diagnosed by their features as well as by the very early onset of serious eye and ear disease. [checkorphan.org]
But hopefully we will also be able to prevent many of the sometimes life-threatening complications. [marshallsmith.org]
[…] of other conditions or disorders (i.e., personality disorders, difficulties distinguishing between reality and fantasy), difficulties with work, the law and court system and/or suicide Prevention of mis-directed treatment Learning about how one thinks [taniaannmarshall.wordpress.com]
“How will I prevent her from having other people make fun of her? I feel like this whole process has been an education for me, because I was never, ever, exposed to anyone at any age with special needs. [nytimes.com]
- Berlucchi M, Meini A, Plebani A, Bonvini MG, Lombardi D, Nicolai P. Update on treatment of Marshall's syndrome (PFAPA syndrome): report of five cases with review of the literature. Ann Otol Rhinol Laryngol. 2003;112(4):365-369.
- Trandafir LM, Chiriac MI, Diaconescu S, Ioniuc I, Miron I, Rusu D. Marshall syndrome in a young child, a reality: Case report. Medicine (Baltimore). 2016;95(44):e5065.
- Salehzadeh F, Vahedi M, Hosseini-Asl S, Jahangiri S, Habibzadeh S, Hosseini-Khotbesara M. PFAPA and 12 Common MEFV Gene Mutations Our Clinical Experience. Iran J Pediatr. 2014;24(1):64-68.
- Ovetchkine P, Bry ML, Reinert P. Marshall syndrome: results of a retrospective national survey [Article in French]. Arch Pediatr. 2000;7(3):578s-582s.
- Stojanov S, Lapidus S, Chitkara P, et al. Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) is a disorder of innate immunity and Th1 activation responsive to IL-1 blockade. Proceedings of the National Academy of Sciences of the United States of America. 2011;108(17):7148-7153.
- Vanoni F, Theodoropoulou K, Hofer M. PFAPA syndrome: a review on treatment and outcome. Pediatric Rheumatology Online Journal. 2016;14:38.
- Thomas KT, Feder HM Jr, Lawton AR, Edwards KM. Periodic fever syndrome in children. J Pediatr. 1999;135(1):15-21.
- Tasher D, Somekh E, Dalal I. PFAPA syndrome: new clinical aspects disclosed. Archives of Disease in Childhood. 2006;91(12):981-984.
- Femiano F, Lanza A, Buonaiuto C, Gombos F, Cirillo N. Oral aphthous-like lesions, PFAPA syndrome: a review. J Oral Pathol Med. 2008;37(6):319-323.