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Marshall's Syndrome

Marshall Syndrome

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.


Presentation

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 [1] [2] [3]. 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 [4]. Their duration is approximately 3-6 days and recurrence is observed every 3-8 weeks [2] [3] [5] [6]. In the asymptomatic period, children report no complaints, and normal growth and development are noted [5]. 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 [7]. 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 [3] [5] [6] [8]. 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 [4] [5] [9]. Apart from a small predilection toward male gender, no other risk factors have been identified [8].

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]
  • Approximately seven multigenerational families have been reported since.2 Short stature, sensorineural hearing loss, and a characteristic facial appearance with hypoplastic nasal bones characterize the syndrome.[healio.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]
Pediatric Disorder
  • disorder first described in 1966 by Marshall et al. in a case series of five African children. [2] The acute phase is characterized by the onset of multiple, erythematous, edematous papules and plaques on face, trunk, and extremities.[ijpd.in]
Recurrent Respiratory Infections
  • 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[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]
Respiratory Distress
Dysphagia
  • 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]
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]
  • Marshall's syndrome or PFAPA (periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis) syndrome is a recently described pediatric periodic disease characterized by recurrent febrile episodes associated with head and neck symptoms.[ncbi.nlm.nih.gov]
  • stomatitis, pharyngitis, cervical adenitis) syndrome is a recently described pediatric periodic disease characterized by recurrent febrile episodes associated with head and neck symptoms.[connection.ebscohost.com]
Bluish Sclerae
  • Many cases, however, have a wider clinical spectrum. general fetal macrosomia failure to thrive skeletal accelerated skeletal maturation craniofacial dysmorphic facial features prominent eyes bluish sclerae coarse eyebrows upturned nose mental retardation[radiopaedia.org]
Cutis Laxa
  • A deficiency of alpha 1-AT may allow proteases such as neutrophil elastase to destroy dermal elastin and, thus, produce cutis laxa in Marshall's syndrome.[ncbi.nlm.nih.gov]
  • Cutis laxa can be inherited or acquired condition. Inherited cutis laxa can be autosomal dominant, recessive, or X-linked. Acquired cutis laxa is rare and can be subdivided into type 1 and type 2.[ijpd.in]
  • Inherited forms comprise autosomal dominant cutis laxa, autosomal recessive cutis laxa, Urban–Rifkin–Davis syndrome, macrocephaly-alopecia-cutis laxa-scoliosis syndrome, arterial tortuosity syndrome and X-linked cutis laxa. [3] , [4] The acquired form[ijdvl.com]
Dermatitis
  • Marshall's syndrome is a form of acquired cutis laxa without systemic involvement, which is preceded by an inflammatory dermatitis with a neutrophilic component.[ncbi.nlm.nih.gov]
  • […] herpetiformis, interstitial granulomatous dermatitis, sarcoidosis and celiac disease have been described to be associated with acquired cutis laxa type 1.[ijdvl.com]
Hyperkeratosis
  • Biopsy taken 8 months back was reviewed, which showed hyperkeratosis, irregular acanthosis and mild spongiosis.[ijpd.in]
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]
Round Face
  • The facial features of Marshall Syndrome include a flat midface, the appearance of large eyes, short upturned nose, and a round face.[en.wikipedia.org]

Workup

Although Marshall's or PFAPA syndrome is considered to be the most common cause of periodic fevers in childhood [5] [6], its diagnosis may be challenging in the absence of clinical suspicion, which is often lacking [8]. 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 [2] [5]. 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 [6] [9]. 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 [4]. 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 [1] [5]. 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 [3].

Chlamydia
  • Trevor Marshall, PhD: Whether the inflammation (which gives rise to the CFS and/or FM symptoms) is caused by Borrelia, Bartonella, Chlamydia, or any other bacterium with the ability to change into these tiny pleomorphic shapes (also called "L-forms,"[prohealth.com]
Polyps
  • Gallbladder polyps in children—classification and management . J Pediatr Surg 2003; 38 : 1680–1684. 8. Shaw AC , van Balkom IDC , Bauer M , Cole TRP , Delruge MA , Van Haeringen A et al . Phenotype and natural history in Marshall-Smith syndrome .[nature.com]

Treatment

  • The etiology remains unknown and there is no definitive treatment.[ncbi.nlm.nih.gov]
  • 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]
  • 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]

Prognosis

  • […] 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]
  • Prognosis has improved considerably in recent years to nearly full life expectancy. However, if left untreated, it can be life threatening.[tall.life]
  • For the last 100 years sarcoidosis patients have been told that there is no known cause and no known cure for their disease (much the same prognosis being given to CFS and FM patients).[prohealth.com]
  • Prognosis Marshall-Smith syndrome has long been considered a childhood condition because affected individuals did not typically survive past childhood..[marshallsmith.org]

Etiology

  • 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]
  • […] arterial tortuosity syndrome and X-linked cutis laxa. [3] , [4] 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. [5] A number of etiologic[ijdvl.com]

Epidemiology

  • 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]
Sex distribution
Age distribution

Prevention

  • 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]
  • Accident Analysis & Prevention (Candrive special issue) 2013;61:236-244.[med.uottawa.ca]
  • Treatment [ edit ] There is no medical treatment for either syndrome but there are some recommendations that can help with prevention or early identification of some of the problems.[en.wikipedia.org]

References

Article

  1. 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.
  2. 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.
  3. 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.
  4. Ovetchkine P, Bry ML, Reinert P. Marshall syndrome: results of a retrospective national survey [Article in French]. Arch Pediatr. 2000;7(3):578s-582s.
  5. 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.
  6. Vanoni F, Theodoropoulou K, Hofer M. PFAPA syndrome: a review on treatment and outcome. Pediatric Rheumatology Online Journal. 2016;14:38.
  7. Thomas KT, Feder HM Jr, Lawton AR, Edwards KM. Periodic fever syndrome in children. J Pediatr. 1999;135(1):15-21.
  8. Tasher D, Somekh E, Dalal I. PFAPA syndrome: new clinical aspects disclosed. Archives of Disease in Childhood. 2006;91(12):981-984.
  9. 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.

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Last updated: 2019-06-28 11:39