What are the other Names for this Condition? (Also known as/Synonyms)

• Acute Febrile Neutrophilic Dermatosis (AFND)
• Gomm-Button Syndrome
• PAAND (Pyrin-Associated Autoinflammation with Neutrophilic Dermatosis)

What is Pyrin-Associated Autoinflammation with Neutrophilic Dermatosis? (Definition/Background Information)

• Pyrin-Associated Autoinflammation with Neutrophilic Dermatosis (PAAND) is a rare genetic disorder that causes recurrent episodes of inflammation and skin rashes. Other presentations include severe hidradenitis suppurativa, pyoderma gangrenosum, fat inflammation, and arthritis
• The disorder is caused by mutations in the MEFV gene (that encodes the pyrin protein) and is inherited in an autosomal dominant manner. Thus, the risk factor for Pyrin-Associated Autoinflammation with Neutrophilic Dermatosis includes a positive family history of the disorder
• It is typically diagnosed based on a combination of clinical examination, molecular genetic testing, and blood tests to measure inflammatory markers. A skin biopsy may be necessary towards establishing a diagnosis of Pyrin-Associated Autoinflammation with Neutrophilic Dermatosis
• The treatment is typically symptomatic and supportive and may include medications, such as non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and treatments directed to decrease Interleukin-1 in order to reduce inflammation and prevent recurrent episodes.
• Currently, there are no available measures to prevent Pyrin-Associated Autoinflammation with Neutrophilic Dermatosis as it is a genetic condition. Genetic counseling and testing may be recommended for individuals with a family history of PAAND and couples planning to have children
• The prognosis is generally good with adequate treatment. With effective treatment, most individuals with Pyrin-Associated Autoinflammation with Neutrophilic Dermatosis can have a good quality of life, although severe cases of the disorder can cause significant discomfort and pain, particularly if left untreated

Who gets Pyrin-Associated Autoinflammation with Neutrophilic Dermatosis? (Age and Sex Distribution)

• Pyrin-Associated Autoinflammation with Neutrophilic Dermatosis is a rare disorder with congenital manifestation (onset of symptoms occur during infancy and early childhood)
• It affects both males and females
• Not enough cases have been reported to determine the frequency and racial/ethnic distribution. However, cases have been reported from France, Spain, Belgium, and Japan

What are the Risk Factors for Pyrin-Associated Autoinflammation with Neutrophilic Dermatosis? (Predisposing Factors)

The risk factors for Pyrin-Associated Autoinflammation with Neutrophilic Dermatosis include:

• Having a family history of the disorder
• Inheriting a copy of the mutated MEFV gene from a parent to develop the disorder

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Pyrin-Associated Autoinflammation with Neutrophilic Dermatosis? (Etiology)

Pyrin-Associated Autoinflammation with Neutrophilic Dermatosis (PAAND) is a genetic disorder caused by mutations in the MEFV gene.

• The MEFV gene encodes the pyrin protein. Mutations in the gene lead to abnormal functioning of the pyrin protein, which is involved in the regulation of inflammation
• The disorder has an autosomal dominant pattern of transmission
• PAAND Syndrome has some clinical similarities to pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome, but it is a distinct disease

The MEFV gene is also causative in Familial Mediterranean Fever (FMF). A different locus on the gene is involved. The two Syndromes have some similar clinical findings but are distinct entities.

Autosomal dominant mode of inheritance: Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a non-sex chromosome. In these types of conditions, the individual has one normal copy and one mutant copy of the gene. The abnormal gene dominates, masking the effects of the correctly function gene. If an individual has an autosomal dominant condition, the chance of passing the abnormal gene on to their offspring is 50%. Children, who do not inherit the abnormal gene, will not develop the condition or pass it on to their offspring.

What are the Signs and Symptoms of Pyrin-Associated Autoinflammation with Neutrophilic Dermatosis?

The most common signs and symptoms of Pyrin-Associated Autoinflammation with Neutrophilic Dermatosis (PAAND) include: 

• Recurrent episodes of fever
• Inflammatory skin findings, which are described as neutrophilic dermatoses, that cause red, swollen, and painful pustular skin lesions
• Muscle and joint inflammation with tenderness, swelling, and pain (myalgia)
• Abdominal pain can be seen, as well as cardiac inflammation with associated dysfunction
• Tender skin lesions, firm and red to purple, can indicate small vessel neutrophilic vasculitis
• Arthritis of large and small joints

The onset of symptoms is most often in childhood. Because of the recent elucidation of PAAND, typically, multiple family members are found with the condition after the diagnosis of one individual.

How is Pyrin-Associated Autoinflammation with Neutrophilic Dermatosis Diagnosed?

Pyrin-Associated Autoinflammation with Neutrophilic Dermatosis is typically diagnosed based on a combination of the following:

• Clinical examination and assessment of presenting signs and symptoms
• Evaluation of family history of the condition
• Blood tests to measure the levels of inflammatory markers
• Skin biopsies to determine and confirm the diagnosis of the various skin lesions
• Genetic testing for alterations in the MEFV gene

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Pyrin-Associated Autoinflammation with Neutrophilic Dermatosis?

Complications of Pyrin-Associated Autoinflammation with Neutrophilic Dermatosis (PAAND) may include:

• Severe pustular skin conditions, such as severe acne, hidradenitis suppurativa, pyoderma gangrenosum, and small vessel neutrophilic vasculitis. These are life-altering conditions based on pain, severity, and disfigurement
• Neutrophilic panniculitis (fat inflammation)
• In children, failure to thrive and developmental delays are seen
• One case of systemic amyloidosis has been reported in PAAND
• Cardiac inflammation led to heart failure in one patient, necessitating a heart transplant
• Overall, reduced quality of life

How is Pyrin-Associated Autoinflammation with Neutrophilic Dermatosis Treated?

A treatment of Pyrin-Associated Autoinflammation with Neutrophilic Dermatosis is typically symptomatic and supportive and may include medications to reduce inflammation and prevent recurrent episodes such as:

• Non-steroidal anti-inflammatory drugs (NSAIDs)
• Corticosteroids
• Potassium iodide tablets or solutions have been used, although they may increase the severity of vasculitis
• Interleukin-1 beta activity-decreasing medications such as anakinra, canakinumab, and rilonacept

How can Pyrin-Associated Autoinflammation with Neutrophilic Dermatosis be Prevented?

Presently, it is not possible to prevent Pyrin-Associated Autoinflammation with Neutrophilic Dermatosis as the cause is a genetic mutation. 

• Genetic counseling and testing may be recommended for individuals with a family history of the disorder and couples planning to have children
• However, early diagnosis and appropriate treatment can help manage the symptoms and prevent complications

What is the Prognosis of Pyrin-Associated Autoinflammation with Neutrophilic Dermatosis? (Outcomes/Resolutions)

The prognosis of Pyrin-Associated Autoinflammation with Neutrophilic Dermatosis is generally good with proper treatment.

• When adequate treatment is provided, most patients can have a good quality of life
• However, the disorder can cause significant discomfort and pain if left untreated.

Additional and Relevant Useful Information for Pyrin-Associated Autoinflammation with Neutrophilic Dermatosis:

A recent article postulates that PAAND and Sweet syndrome are the same diseases. This may prove true after genetic testing on more patients who fall into the Sweet syndrome diagnostic criteria.