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Muckle Wells Syndrome

Muckle-Wells syndrome

Muckle Wells syndrome (MWS) is a rare genetic disorder that causes recurrent episodes of fever, skin rash, arthralgia/arthritis, and inflammation of the eye. Additionally, it is associated with serious complications such as bilateral sensorineural deafness and amyloidosis.


Presentation

CAPS consists of three different diseases that are classified in terms of clinical pictures, organ involvement, severity, as well as triggers. They share similar features as well.

MWS manifests in infancy or childhood and continues onwards. Its symptoms include intermittent mild-to-moderate fever, recurrent non-itchy rashes, arthritis/arthralgia, malaise, and chills. Additionally, eye pathology such as conjunctivitis, uveitis, and episcleritis are observed in these patients. Furthermore, progressive bilateral sensorineural hearing loss is common and develops in adolescence, early adulthood or beyond. Headaches as a result of aseptic meningitis can occur as well. Amyloidosis of the organs such as the kidneys may develop in approximately one-third of patients. Finally, pigmented skin lesions are observed in individuals with MWS.

These attacks can occur spontaneously or may be a consequence of triggers such as cold weather, exercise, or stress. Note that while exposure to cold temperatures is a common trigger of FCAS, it is an infrequent precipitating factor in MWS. Moreover, the episodes are usually random and last for a duration of less than 36 hours although they can continue for five days. The patient usually feels well between these acute relapses.

Physical exam

Remarkable findings include lymphadenopathy and/or hepatosplenomegaly. Also, arthritis of the large joints, skin rashes, skin discoloration, and inflammatory eye conditions such as conjunctivitis are remarkable on the exam during flare-ups.

Splenomegaly
  • Conjunctivitis Pink eye 0000509 Cranial nerve paralysis 0006824 Episcleritis Inflammation of the thin layer on top of the white part of eye 0100534 Hepatomegaly Enlarged liver 0002240 Progressive sensorineural hearing impairment 0000408 Skin rash 0000988 Splenomegaly[rarediseases.info.nih.gov]
Fever
  • A 26-year-old Japanese woman had suffered at birth from an urticarial rash and episodic fever. The fever was frequently associated with chills and ill-defined malaise. There was no familial history of urticarial rash or fever.[ncbi.nlm.nih.gov]
  • These findings promote awareness of these hereditary periodic fever syndromes as a cause for recurrent fevers from childhood in the Indian population.[ncbi.nlm.nih.gov]
  • MWS is characterized by a moderate phenotype with fever, rash, arthralgia, conjunctivitis, sensorineural deafness, and potentially life-threatening amyloidosis.[ncbi.nlm.nih.gov]
  • Muckle-Wells syndrome (MWS) is a rare disorder inherited in an autosomal-dominant fashion that belongs to a group of hereditary periodic fever syndromes.[ncbi.nlm.nih.gov]
  • Abstract Familial cold autoinflammatory syndrome (FCAS, MIM 120100), commonly known as familial cold urticaria (FCU), is an autosomal-dominant systemic inflammatory disease characterized by intermittent episodes of rash, arthralgia, fever and conjunctivitis[ncbi.nlm.nih.gov]
Amyloidosis
  • We describe a family with nephropathy and several symptoms of MWS, but no evidence of deafness or amyloidosis.[ncbi.nlm.nih.gov]
  • A case of hereditary AA amyloidosis with Muckle-Wells syndrome is described.[ncbi.nlm.nih.gov]
  • SAA can deposit in organs such as the kidneys, resulting in amyloidosis and amyloidosis-induced renal failure.[symptoma.com]
  • Progressive nerve deafness develops subsequently, and, after several years, the disease is complicated by multiorgan AA-type amyloidosis (i.e., amyloidosis derived from the inflammatory serum amyloid-associated protein) (MIM 191900) with renal involvement[ncbi.nlm.nih.gov]
  • Epithelioid histiocytes have been demonstrated in other parts of the body in patients with MWS including the skin and joints, which is sometimes accompanied by amyloidosis.[ncbi.nlm.nih.gov]
Chills
  • Muckle-Wells syndrome (MWS) is a rare syndrome, characterized by chronic recurrent urticaria, often combined with fever, chills, rigors, malaise, and arthralgia.[ncbi.nlm.nih.gov]
  • Intense general malaise and chills occur at the same time and lead to severe disability.[orpha.net]
  • The fever was frequently associated with chills and ill-defined malaise. There was no familial history of urticarial rash or fever. Although she did not recognize hearing loss, audiometry revealed perceptive deafness.[ncbi.nlm.nih.gov]
Fatigue
  • Those diagnosed as adults described musculoskeletal symptoms (86%), rash (67%), hearing loss (52%), and fatigue (29%). Hearing loss was associated with late diagnosis, while access-to-care variables were not predictive.[ncbi.nlm.nih.gov]
  • Cold, fatigue, stress, or exercise are universal triggers of acute inflammation however acute attacks may appear unprovoked.[orpha.net]
  • The most frequent, but not obligate symptoms are familial fatigue, hearing loss, and arthralgia.[ncbi.nlm.nih.gov]
Malaise
  • Muckle-Wells syndrome (MWS) is a rare syndrome, characterized by chronic recurrent urticaria, often combined with fever, chills, rigors, malaise, and arthralgia.[ncbi.nlm.nih.gov]
  • Intense general malaise and chills occur at the same time and lead to severe disability.[orpha.net]
  • Muckle-Wells syndrome is characterized by a recurrent urticarial eruption that is associated with episodic fever, myalgia, arthralgia, malaise, progressive sensorineural hearing loss, and amyloid nephropathy (the most severe complication).[ncbi.nlm.nih.gov]
Abdominal Pain
  • Patients diagnosed during childhood reported musculoskeletal symptoms (62%), rash (62%), fever (54%), and abdominal pain (31%). Those diagnosed as adults described musculoskeletal symptoms (86%), rash (67%), hearing loss (52%), and fatigue (29%).[ncbi.nlm.nih.gov]
  • A 23-year-old woman had recurrent self-limited inflammatory episodes from childhood, with headache, abdominal pain, arthritis, and urticarial rash, associated with profound sensorineural hearing loss.[ncbi.nlm.nih.gov]
  • It is characterized by recurrent inflammatory crises associated with fever, abdominal pain, persistent urticaria, arthralgia, sensorineural deafness, and possible development of multiorgan amyloid A protein (AA)-type amyloidosis.[ncbi.nlm.nih.gov]
  • Abstract The Muckle-Wells syndrome (MWS) is a hereditary inflammatory disorder characterized by acute febrile inflammatory episodes comprising abdominal pain, arthritis, and urticaria.[ncbi.nlm.nih.gov]
  • The other manifestations included polyarthralgia/arthritis (n 3), oral ulcers (n 2), conjunctivitis (n 2), myalgia (n 2), headache (n 2), pharyngitis (n 1), abdominal pain (n 1), severe sensorineural hearing loss (n 1), and chronic meningitis with communicating[ncbi.nlm.nih.gov]
Nausea
  • The most common adverse effects include nasopharyngitis, rhinitis, nausea, diarrhea, and vertigo. 4 In one study, most patients did not report injection-site reactions. 7 Studies also are underway on VX-765, a caspace-1 targeted therapy that acts upstream[mdedge.com]
  • ), weight gain, injection site reactions (such as redness, swelling, warmth, or itching), and nausea.[ilaris.com]
  • Other symptoms include fever, chills, nausea, extreme thirst, headache and joint pain.[arthritis.org]
  • The most recent episodes had also been accompanied by abdominal discomfort, nausea, and anorexia. Symptoms required prolonged rest and slowly dissipated with the help of antipyretics and corticosteroids.[revistanefrologia.com]
Aphthous Ulceration
  • Associated findings may include renal amyloidosis (and renal insufficiency), aminoaciduria, conjunctivitis, abdominal pain, angioedema, meningitis, and aphthous ulceration of the buccal mucosa.[accessanesthesiology.mhmedical.com]
Hepatomegaly
  • Joint pain 0002829 Arthritis Joint inflammation 0001369 Broad foot Broad feet Wide foot [ more ] 0001769 Conjunctivitis Pink eye 0000509 Cranial nerve paralysis 0006824 Episcleritis Inflammation of the thin layer on top of the white part of eye 0100534 Hepatomegaly[rarediseases.info.nih.gov]
Hepatosplenomegaly
  • She also had hepatosplenomegaly and hyperimmunoglobulinemia, but did not have persistent arthritis, or any neurological or gastrointestinal disorder. No growth retardation was observed.[ncbi.nlm.nih.gov]
  • Physical exam Remarkable findings include lymphadenopathy and/or hepatosplenomegaly.[symptoma.com]
  • Also, patients develop osteopathy and long-bone epiphyseal overgrowth, growth delay, and progressive sensory neural hearing loss, lymphadenopathy, with/or without hepatosplenomegaly.[clevelandclinicmeded.com]
Conjunctival Hyperemia
  • CASE 3 Male patient, aged 20, presents episodes of urticaria, conjunctival hyperemia ( Figure 5 ) and arthralgia in the knees, since early infancy, that gets worse with exposure to the cold.[scielo.br]
Urticaria
  • Muckle-Wells syndrome (MWS) is a rare autosomal dominant hereditary disorder characterized by chronic recurrent urticaria, arthralgia, sensorineural deafness, and in some cases nephropathy due to amyloidosis (AA type).[ncbi.nlm.nih.gov]
  • Abstract The term Muckle-Wells syndrome (MWS) describes an autosomal dominant disorder characterised by various combinations of urticaria, sensorineural deafness, amyloidosis, arthralgia and skeletal abnormalities.[ncbi.nlm.nih.gov]
  • From Wikidata Jump to navigation Jump to search Human disease Uda Syndrome Cryopyrin-Associated Periodic Syndrome 2 MUCKLE-WELLS SYNDROME; MWS MWS Urticaria-Deafness-Amyloidosis Syndrome MUCKLE-WELLS SYNDROME Neutrophilic urticaria edit English Muckle-Wells[wikidata.org]
  • It is a subset of auto-inflammatory diseases characterised by recurrent inflammatory crises and is associated with chronic recurrent urticaria, sensorineural deafness, periodic arthritis and secondary amyloidosis.[ncbi.nlm.nih.gov]
  • Abstract Mutations of CIAS1 have recently been shown to underlie familial cold urticaria (FCU) and Muckle-Wells syndrome (MWS), in three families and one family, respectively.[ncbi.nlm.nih.gov]
Skin Lesion
  • Herein we describe six cases of MWS showing, in addition to the classic features of MWS, unique skin lesions that to the best of our knowledge have not been described before in association with MWS.[ncbi.nlm.nih.gov]
  • CONCLUSIONS: Cold-induced skin lesions in Muckle-Wells syndrome represent typical generalized cold air/wind inflammatory reactions, as also observed in familial cold urticaria.[ncbi.nlm.nih.gov]
  • In addition, pigmented skin lesions may occur in affected individuals. Muckle-Wells syndrome is a rare disorder. It has been reported in many regions of the world, but its prevalence is unknown.[ghr.nlm.nih.gov]
  • Genetic sequence analysis of NLRP3 was performed in an MWS patient who presented with periodic fever, arthralgia, and multiform skin lesions. NLRP3 was also analyzed in this patient's parents and 50 healthy individuals.[ncbi.nlm.nih.gov]
Eruptions
  • Muckle-Wells syndrome is characterized by a recurrent urticarial eruption that is associated with episodic fever, myalgia, arthralgia, malaise, progressive sensorineural hearing loss, and amyloid nephropathy (the most severe complication).[ncbi.nlm.nih.gov]
  • Three main features of the disease are: (i) urticarial eruptions; (ii) progressive perceptive deafness; and (iii) amyloid nephropathy. A 26-year-old Japanese woman had suffered at birth from an urticarial rash and episodic fever.[ncbi.nlm.nih.gov]
  • Skin eruptions, with weals of 0.2-3 cm, lasted from 5 to 24 h and were associated with local itching or pain as well as fever, malaise and chills.[ncbi.nlm.nih.gov]
  • It is characterized by a chronic urticarial eruption that starts early in infancy or childhood. The distribution of the cutaneous eruption is widespread and favors the arms and legs over the face and trunk.[mdedge.com]
  • Methods: : A 46-year old man with urticaria-like skin eruptions, periodic fever, arthralgias and sensorineural hearing loss was referred for ophthalmological evaluation. MWS was suspected.[iovs.arvojournals.org]
Hyperpigmentation
  • Describe six cases of sclerodermoid lesions, with hyperpigmentation, sclerosis and hypertrichosis 4.[scielo.br]
  • […] joints of the extremities), chronic headache, and irritability secondary to increased intracranial pressure due to chronic aseptic meningitis of mild intensity, demyelinating lesions, 14 cutaneous lesions (aphthosis, ichthyosis, hypertrichosis, and hyperpigmentation[revistanefrologia.com]
Skin Discoloration
  • Also, arthritis of the large joints, skin rashes, skin discoloration, and inflammatory eye conditions such as conjunctivitis are remarkable on the exam during flare-ups.[symptoma.com]
Progressive Sensorineural Deafness
  • Progressive sensorineural deafness, and, in approximately one third of the patients, amyloidosis of the kidneys as well as of other organs may occur. It was first described in 1962 by Muckle and Wells.[ncbi.nlm.nih.gov]
  • Definition A hereditary periodic fever syndrome characterized by fever, chronic recurrent urticaria, arthralgias, progressive sensorineural deafness, and reactive renal amyloidosis.[uniprot.org]
  • For example, an audiogram is useful to assess the progressive sensorineural deafness. Additionally, a renal biopsy and an evaluation of the urinary protein should be performed to detect the presence of amyloidosis.[symptoma.com]
  • DEFINITION Muckle Wells Syndrome is a dominantly inherited autoinflammatory disease characterized by rashes, fever, arthralgia, progressive sensorineural deafness, and the frequent development of systemic amyloidosis.[flipper.diff.org]
Arthritis
  • Muckle-Wells syndrome is a rare autosomal dominant disorder characterized by chronic recurrent urticaria, periodic arthritis, sensorineural deafness, general signs of inflammation, and secondary amyloidosis (AA type).[ncbi.nlm.nih.gov]
  • A 23-year-old woman had recurrent self-limited inflammatory episodes from childhood, with headache, abdominal pain, arthritis, and urticarial rash, associated with profound sensorineural hearing loss.[ncbi.nlm.nih.gov]
  • Drug Indication Risks Benefits NSAIDS Arthritis; pain, fever Adverse reactions Reduce fever, pain, arthritis Corticosteroids Fever, arthritis,serositis, urticaria, vasculitis Adverse reactions Relieve fever, rash, arthritis, serositis Infliximab Chronic[clinicaladvisor.com]
  • It is a subset of auto-inflammatory diseases characterised by recurrent inflammatory crises and is associated with chronic recurrent urticaria, sensorineural deafness, periodic arthritis and secondary amyloidosis.[ncbi.nlm.nih.gov]
Arthralgia
  • Abstract The term Muckle-Wells syndrome (MWS) describes an autosomal dominant disorder characterised by various combinations of urticaria, sensorineural deafness, amyloidosis, arthralgia and skeletal abnormalities.[ncbi.nlm.nih.gov]
  • Muckle-Wells syndrome (MWS) is a rare condition characterized by urticaria, arthralgias, deafness and amyloid nephropathy. The arthropathy is poorly documented. We describe the arthropathy occurring in four cases of MWS and discuss the management.[ncbi.nlm.nih.gov]
  • Muckle-Wells syndrome (MWS) is a rare autosomal dominant hereditary disorder characterized by chronic recurrent urticaria, arthralgia, sensorineural deafness, and in some cases nephropathy due to amyloidosis (AA type).[ncbi.nlm.nih.gov]
  • Muckle-Wells syndrome (MWS) is a rare syndrome, characterized by chronic recurrent urticaria, often combined with fever, chills, rigors, malaise, and arthralgia.[ncbi.nlm.nih.gov]
  • Muckle-Wells syndrome (MWS) is a dominantly inherited autoinflammatory disease characterized by rashes, fever, arthralgia, sensorineural deafness, and the possible development of systemic AA amyloidosis.[ncbi.nlm.nih.gov]
Myalgia
  • Myalgia, arthralgias and distal edema are very common. With age, patients develop eythematous band over the hands as well as digital clubbing.[orpha.net]
  • It is characterized by recurrent and self-limited episodes of fever, urticaria, arthralgia, myalgia and conjunctivitis since childhood, which are related to exposure to cold temperatures. Lately, progressive sensorineural hearing loss occurs.[ncbi.nlm.nih.gov]
  • It is characterized by recurrent self-limiting episodes of fever, urticaria, arthralgia, myalgia and conjunctivitis from childhood. Progressive sensorineural hearing loss and amyloidosis are two late complications.[ncbi.nlm.nih.gov]
Ankle Pain
  • Back pain, joint and ankle pain, GI issues, some headaches, plugged ears and ear infections, fatigue are def. daily and some are weekly issues. He also has many tics and neuro. issues that show daily. I will try to give you a call for sure.[rareshare.org]
Knee Pain
  • Even my husband wasn't understanding our sons battle with itching and knee pain. I was told Kids just get these things and since it goes away don't worry.[rareconnect.org]
Headache
  • A 23-year-old woman had recurrent self-limited inflammatory episodes from childhood, with headache, abdominal pain, arthritis, and urticarial rash, associated with profound sensorineural hearing loss.[ncbi.nlm.nih.gov]
  • Additional features include severe chronic fatigue, recurrent headaches, cognitive impairment, ocular involvement (conjunctivitis, uveitis, episcleritis), oral aphthosis, lymphadenopathy, thoracic and abdominal pain.[orpha.net]
  • Our three cases had recurrent headache and two of them had enlarged ventricles and cerebellomedullary cisterns in cranial MR.[acrabstracts.org]
Dizziness
  • Call your healthcare provider right away if you have any of these symptoms of an allergic reaction: rash, itching and hives, difficulty breathing or swallowing, dizziness, or feeling faint. risk of infection with live vaccines.[ilaris.com]
Renal Impairment
  • Amyloidosis caused by chronic inflammation is the most serious complication of MWS and is seen in approximately one-third of patients, manifesting as proteinuria followed by renal impairment.[mdedge.com]
  • Associated conditions, disease complications, and sequelae, including hearing impairment or loss, renal impairment, and delayed puberty, were recorded.[arthritis-research.biomedcentral.com]

Workup

The clinical workup consists of an evaluation of the overall clinical presentation, a thorough history including that of the patient's family, a physical examination, and relevant studies.

Laboratory tests

Diagnosis of MWS is definitively proven through genetic testing that reveals the NLRP3 mutation. However, the mutation is not always present in individuals with MWS.

There are numerous abnormal studies in patients with acute episodes. The nonspecific findings include an increase in the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and SAA, which are collectively considered to be acute phase reactants. Additionally, the complete blood count depicts leukocytosis and anemia of chronic disease. Finally, the cerebrospinal fluid (CSF) may demonstrate the presence of neutrophils and eosinophils in the absence of infection.

Special consideration

The workup should be tailored to evaluate the complications associated with MWS. For example, an audiogram is useful to assess the progressive sensorineural deafness. Additionally, a renal biopsy and an evaluation of the urinary protein should be performed to detect the presence of amyloidosis. Note that an initial sign of amyloidosis is proteinuria without red or white blood cells.

Hypocalciuria
  • The routine urine-test diagnosed hypocalciuria. Histopathological exams of the skin showed only chronic dermatitis. Genetic studies showed normal karyotype and the research on chromosome breakage was negative.[scielo.br]

Treatment

The main therapeutic approach for MWS and other CAPS diseases is the inhibition of IL-1 especially in patients with an earlier onset and more severe manifestations [9]. It is paramount to initiate treatment early in order to control the risk of developing hearing loss [8] and amyloidosis.

The IL-1 antagonist known as Rilonacept is a dimeric fusion protein that is FDA approved for MWS patients 12 years and older. Another drug in the same category, Kineret, is not FDA approved yet for MVS but has demonstrated success in many MWS patients. Overall, IL-1 inhibitors are associated with a good prognosis as they reduce the risk for developing sensorineural deafness.

Another medication used in children and adults with this disease is Canakinumab, an FDA-approved monoclonal antibody against IL-1β. This drug elicits good control in patients but may require dose adjustments throughout treatment [10].

Other

Hearing loss can be improved with hearing aids and other similar medical technologies.

Arthralgia and arthritis can be alleviated with non-steroidal anti-inflammatory drugs (NSAIDS). Moreover, corticosteroids administered in high doses can be useful but they place the patients at risk for adverse effects both in short and long-term.

If present, renal failure secondary to amyloidosis will be managed accordingly.

Prognosis

Progressive deafness and renal failure are serious complications in this disease. However, the prognosis is promising in those treated with IL-1 inhibitors. Specifically, sensorineural deafness responds well to this class of drugs [9]. Additionally, therapy with IL-1 antagonists can decrease the risk of amyloidosis as untreated individuals have a 25% risk of developing this sequela. Since amyloidosis nephropathy is associated with mortality, early recognition and treatment are essential.

Etiology

The etiology of MWS is attributed to mutations in the NLRP3 gene (found on chromosome 1), which is transmitted in an autosomal dominant pattern. This gene codes for the cryopyrin protein [3], which is a component of the NLRP3 inflammasome along with procaspase 1. The NLRP3 inflammasome plays a key role in the activation of caspase 1, which induces the cleavage of pro-IL-1β to produce IL-1β [4]. The latter is released from cells. In this disease, there is an occasional excessive production of IL-1β that accounts for the acute inflammatory attacks consisting of fever, rash, conjunctivitis, and musculoskeletal involvement.

Epidemiology

The prevalence of CAPS is approximately 1 per population of 400,000 [5].

Sex distribution
Age distribution

Pathophysiology

The CAPS are caused by a mutation in the NLRP3 gene, which codes for cryopyrin, a protein with an integral role in the regulation of inflammation and apoptosis. This mutation activates the NLRP3 inflammasome [6], which stimulates a series of cellular mechanisms that ultimately release inflammatory cytokines such as IL-1. The latter is spontaneously secreted by macrophages in these patients [7].

IL-1 has numerous functions which include increasing the production of serum amyloid A (SAA) by the liver. SAA can deposit in organs such as the kidneys, resulting in amyloidosis and amyloidosis-induced renal failure.

Another severe sequela arising from MWS is bilateral sensorineural hearing loss secondary to chronic inflammation mediated by IL-1 in the cochlea [8].

Prevention

There are no preventative measures for MWS since it is an inherited disorder. But patients and their family members planning on starting families can seek prenatal care to gain understanding about what MWS entails, the probability of transmitting the disease, and further details. Additionally, genetic testing may be offered in appropriate cases.

Summary

Muckle Wells Syndrome (MWS), also referred to as urticaria-deafness-amyloidosis syndrome, is a rare autosomal dominant disorder that falls within the spectrum of hereditary periodic fever diseases [1]. Furthermore, this autoinflammatory condition is the moderate form of three clinical phenotypes that comprise the cryopyrin-associated periodic syndromes (CAPS). The two other phenotypes are known as familial cold autoinflammatory syndrome (FCAS) (mildest) and chronic infantile neurologic cutaneous articular syndrome (CINCA syndrome) or neonatal-onset multisystem inflammatory disease (NOMID) (most severe) [2]. The mutation responsible for CAPS involves the NLRP3 gene, which encodes cryopyrin. This is a pivotal protein in the pathway that synthesizes interleukin-1β (IL-1β), which is the cause of the clinical features observed in CAPS patients.

The symptomology of MWS is characterized by recurrent episodes of fevers, urticaria, headaches, and inflammatory signs such as arthralgia and ophthalmic manifestations including conjunctivitis and uveitis. The onset of MWS occurs in infancy or childhood. Serious complications include progressive bilateral sensorineural hearing loss and amyloidosis with the latter leading to nephropathy. These attacks typically last less than 36 hours.

The clinical assessment consists of the individual's personal and family history, a physical exam, and appropriate studies. The confirmatory diagnostic tool is the genetic detection of the mutation in the NLRP3 gene. Other tests include the measurements of the acute phase reactants, which are typically abnormal during the flare-ups. Additionally, an audiogram is important as is an evaluation of amyloid nephropathy with renal biopsy when indicated.

MWS (and other CAPS) is treated with IL-1 inhibitors, which is successful in controlling the progression of hearing loss and lowering the risk of developing amyloidosis. Additionally, there is a monoclonal antibody that is effective in treating MWS. Furthermore, there are other measures that can be used for symptom relief. Finally, genetic counseling is available for patients and their family members who desire to start families.

Patient Information

What is Muckle Wells syndrome?

Muckle Wells syndrome (MWS) is a genetic disorder, in which the affected individuals experience repeating flare-ups of fever, non-itchy rash, and joint pain/swelling along with eye problems. These episodes can occur randomly, but they also may be triggered by cold temperatures. They usually last less than three days but may continue for up to five days.

Who is affected by MWS?

This disease begins in young infants and children. It occurs because of a mutation in the NLRP3 gene that produces a protein called cryopyrin. This mutation ultimately causes an excessive production of a protein called interleukin-1β, which is responsible for the inflammatory symptoms seen in these patients.

MWS is inherited in an autosomal dominant pattern, which means that the patient receives one bad copy of the gene from the affected parent and one good copy from the nonaffected parent. To explain further, the affected patient has 50% chance of passing this disease to offspring.

What are the signs and symptoms of MWS?

The following are the main features of the flare-ups:

Complications of MWS include:

How is MWS diagnosed?

The clinician will obtain the personal and family history of the patient, perform a physical exam, and run important tests. The genetic test that confirms MWS reveals the mutation in the NLRP3 genes. However, not all patients have this mutation.

Patients with MWS will have abnormal laboratory tests during their flare-ups. For example, they have an increased number of white blood cells as well anemia of chronic disease. Also, they have increased erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and serum amyloid A (SAA).

Other important studies for MWS patients include an audiogram to test for the progressive loss of hearing. Also, a urinary protein test and renal biopsy can assess for amyloidosis.

How is MWS treated?

The main treatment for MWS includes a class of drugs known as interleukin-1 inhibitors, which block interleukin-1. Two examples are Rilonacept and Kineret. These produce good results and decrease the risk of the patient developing hearing loss.

There is another drug known as Canakinumab, which acts as an antibody against interleukin-1.

Note that non-steroidal anti-inflammatory drugs (NSAIDS) are effective for joint pain and swelling. Also, corticosteroids are helpful but they are associated with side effects.

Finally, patients with hearing loss will benefit from hearing aids.

What is the prognosis?

Treatment with interleukin-1 blockers yields good results in patients.

Can it be prevented?

Since this is a genetic disease, it cannot be prevented. But affected individuals and their family members may obtain genetic counseling to gain an understanding about the disease and learn about the chances of passing it to an offspring. Also, genetic testing may be offered as well.

References

Article

  1. McDermott MF, Frenkel J. Hereditary periodic fever syndromes. Netherlands Journal of Medicine. 2001; 59(3):118-25.
  2. Aksentijevich I, Nowak M, Mallah M et al. De novo CIAS1 mutations, cytokine activation, and evidence for genetic heterogeneity in patients with neonatal-onset multisystem inflammatory disease (NOMID): a new member of the expanding family of pyrin-associated autoinflammatory diseases. Arthritis and Rheumatism. 2002; 46(12): 3340–8.
  3. Stojanov S, Kastner DL. Familial autoinflammatory diseases: genetics, pathogenesis and treatment. Current Opinion in Rheumatology. 2005;17(5): 586–99.
  4. Martinon F, Mayor A, Tschopp J. The inflammasomes: guardians of the body. Annual Review of Immunology. 2009; 27: 229–65.
  5. Cuisset L, Jeru I, Dumont B, et al; for the French CAPS study group. Mutations in the autoinflammatory cryopyrin-associated periodic syndrome gene: epidemiological study and lessons from eight years of genetic analysis in France. Annals of the Rheumatic Diseases. 2011; 70(3):495-9.
  6. Fujisawa A, Kambe N, Saito M, et al. Disease-associated mutations in CIAS1 induce cathepsin B-dependent rapid cell death of human THP-1 monocytic cells. Blood. 2007; 109(7):2903-11.
  7. Agostini L, Martinon F, Burns K, et al. NALP3 forms an IL-1beta-processing inflammasome with increased activity in Muckle-Wells autoinflammatory disorder. Immunity. 2004; 20(3):319-25.
  8. Ahmadi N, Brewer CC, Zalewski C, et al. Cryopyrin-associated periodic syndromes: otolaryngologic and audiologic manifestations. Otolaryngology Head and Neck Surgery. 2011;145(2):295-302.
  9. Goldbach-Mansky R, Dailey NJ, Canna SW, et al. Neonatal-onset multisystem inflammatory disease responsive to interleukin-1β inhibition. New England Journal of Medicine. 2006; 355(6):581–92.
  10. Caorsi R, Lepore L, Zulian F, et al. The schedule of administration of canakinumab in cryopyrin associated periodic syndrome is driven by the phenotype severity rather than the age. Arthritis Research and Therapy. 2013;15(1):R33.

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Last updated: 2019-07-11 21:00