The syndromes within CAPS overlap clinically, and patients may have features of more than one disorder. In a retrospective cohort of 136 CAPS patients from 16 countries, the most prevalent clinical features were fever (84% of cases, often with concurrent constitutional symptoms such as fatigue, malaise, mood disorders or failure to thrive), skin rash (either urticarial or maculopapular rash; 97% of cases) especially after cold exposure, and musculoskeletal involvement (myalgia, arthralgia, and/or arthritis, or less commonly joint contracture, patellar overgrowth, bone deformity, bone erosion and/or osteolytic lesion; 86% of cases). Less common features included ophthalmological involvement (conjunctivitis and/or uveitis, or less commonly optic nerve atrophy, cataract, glaucoma or impaired vision; 71% of cases), neurosensory hearing loss (42% of cases), neurological involvement (morning headache, papilloedema, and/or meningitis, or less commonly seizure, hydrocephalus or mental retardation; 40% of cases), and AA amyloidosis (4% of cases). Age of onset is typically in infancy or early childhood. In 57% of cases, CAPS had a chronic phenotype with symptoms present almost daily, whereas the remaining 43% of patients experienced only acute episodes. Up to 56% of patients reported a family history of CAPS. Previous studies confirm these symptoms, although the exact reported rates vary.

TNF receptor associated periodic syndrome presents with the following signs and symptoms:

- Episodic fever

- Erythrocyte sedimentation rate(increased)

- Pericarditis

- Splenomegaly

- Uveitis

- Vertigo

Cryopyrin-associated periodic syndrome (CAPS) is a group of rare, heterogeneous autoinflammatory disease characterized by interleukin 1β-mediated systemic inflammation and clinical symptoms involving skin, joints, central nervous system, and eyes. It encompasses a spectrum of three clinically overlapping autoinflammatory syndromes including familial cold autoinflammatory syndrome (FCAS, formerly termed familial cold-induced urticaria), the Muckle–Wells syndrome (MWS), and neonatal-onset multisystem inflammatory disease (NOMID, also called chronic infantile neurologic cutaneous and articular syndrome or CINCA) that were originally thought to be distinct entities, but in fact share a single genetic mutation and pathogenic pathway.

TNF receptor associated periodic syndrome (also known as TRAPS,) is a periodic fever syndrome associated with mutations in a receptor for the molecule tumor necrosis factor (TNF) that is inheritable in an autosomal dominant manner. Individuals with TRAPS have episodic symptoms such as recurrent high fevers, rash, abdominal pain, joint/muscle aches and puffy eyes.

The age of onset is almost always before 3 months of age. Many infants are born preterm (1/3 cases) and dysmature. The babies are frequently small for dates. The placenta may be abnormal with non-specific inflammation on histology. Umbilical cord anomalies have occasionally been reported. In severe cases, signs in the brain may be detected on prenatal ultrasound.

The presentation is pleiomorphic, making the diagnosis difficult, but the most common features of this disease involve the skin, joints, and central nervous system.

All have a maculopapular urticarial skin rash that is often present at birth (75% cases). It is probably more correctly described as an urticarial-like rash. The presence of the rash varies with time, and biopsy of these skin lesions shows a perivascular inflammatory infiltrate including granulocytes.

In about 35-65% of cases, arthritis occurs. Joint signs are variably expressed and can lead to transient swelling without sequelae between crises, or to unpredictable anomalies of growth cartilage and long bones epiphyses suggestive of a pseudo-tumour. Biopsies reveal hypertrophic cartilage without inflammatory cells. This most commonly affects the large joints (knees, ankles, elbows, and wrists) but may also involve the small joints of the hands and feet. It is usually bilateral and painful. A common and characteristic feature is giant kneecaps. Severe cases may result in contractures (joint deformities).

Most patients eventually have neurological problems. These manifest themselves in three principal ways: chronic meningitis, involvement of both the optic tract and eye, and sensorineural hearing loss. The chronic meningitis presents with the features of chronically raised intracranial pressure: headaches, vomiting, ventriculomegaly, hydrocephalus, macromegaly, cerebral atrophy, and optic atrophy. Some of these features may be evidenced on prenatal ultrasound. In 50% of cases, intellectual deficit occurs. Seizures occur in 25% of cases, but other manifestations are rare. Histological examination shows infiltration of the meninges with polymorphs.

Ocular manifestations occur in 80% of cases and include uveitis (70%), papillary involvement, conjunctivitis, and optical neuritis. If untreated, these may result in blindness (25%). The sensorineural hearing loss occurs in 75%, and tends to be progressive leading to deafness in 20% of cases.

Almost all children are remarkably short and have growth delay. Fever is extremely common but inconstant and is most often mild. Anemia is frequent. Other findings that have been reported include macrocephaly (95%), large fontanelle, prominent forehead, flattening of the nasal bridge (saddleback nose), short and thick extremities, and finger clubbing. The liver and/or spleen may be enlarged. Lymph node enlargement may also be present.

Later in life, secondary amyloidosis may occur. Delayed puberty and secondary amenorrhoea are not uncommon. Hoarseness due to inflammation of the laryngeal cartilage has also been reported.

The symptoms of CANDLE syndrome can manifest themselves in a variety of different ways and combinations related to skin disorders, internal inflammatory responses, and fever-based conditions. The types of outwardly visible conditions involve facies not matching other known disorders, contracture of the joints, and skin lesions appearing across any part of the body. The multiple inflammatory developments include nonspecific lymphadenopathy, hepatosplenomegaly, and autoimmune hemolytic anemia. Other possible conditions are hypertriglyceridemia and lipodystrophy.

Other novel mutations resulting in the syndrome have also involved the manifestation of other conditions, such as Sweet's syndrome and pericarditis. Another case in 2015 showcased previously undescribed dental symptoms, such as microdontia and osteopenia of the jaw, along with a general case of diabetes mellitus.

Neonatal-onset multisystem inflammatory disease (abbreviated NOMID, also known as chronic infantile neurologic cutaneous and articular syndrome, or CINCA) is a rare genetic periodic fever syndrome which causes uncontrolled inflammation in multiple parts of the body starting in the newborn period. Symptoms include skin rashes, severe arthritis, and chronic meningitis leading to neurologic damage. It is one of the cryopyrin-associated periodic syndromes.

NOMID can result from a mutation in the "CIAS1" gene (also known as "NLRP3" gene), which helps control inflammation. Mutations in this gene also cause familial cold urticaria and Muckle–Wells syndrome. NOMID has been successfully treated with the drug anakinra.

This syndrome is also known as the Prieur–Griscelli syndrome as it was first described by these authors in 1981.

Chronic Atypical Neutrophilic Dermatosis with Lipodystrophy and Elevated Temperature (CANDLE) syndrome is an autosomal recessive disorder that presents itself via various autoinflammatory responses throughout the body, multiple types of skin lesions, and recurrent long-term fever symptoms. The current known cause for the disorder is a mutation in the PSMB8 gene or mutations in other closely related genes. The syndrome was first named and classified in March 2010 after four patients were reviewed with similar symptoms. There have been approximately 30 cases ever reported in the scientific literature, as of 2015.

HIDS is one of a number of periodic fever syndromes. It is characterised by attacks of fever, arthralgia, skin lesions including cyclical mouth ulcers, and diarrhea. Laboratory features include an acute phase response (elevated CRP and ESR) and markedly elevated IgD (and often IgA), although cases with normal IgD have been described.

It has mainly been described in the Netherlands and France, although the international registry includes a number of cases from other countries.

The differential diagnosis includes fever of unknown origin, familial Mediterranean fever (FMF) and familial Hibernian fever (or TNFα reception associated periodic syndrome/TRAPS).

The precise symptoms of a primary immunodeficiency depend on the type of defect. Generally, the symptoms and signs that lead to the diagnosis of an immunodeficiency include recurrent or persistent infections or developmental delay as a result of infection. Particular organ problems (e.g. diseases involving the skin, heart, facial development and skeletal system) may be present in certain conditions. Others predispose to autoimmune disease, where the immune system attacks the body's own tissues, or tumours (sometimes specific forms of cancer, such as lymphoma). The nature of the infections, as well as the additional features, may provide clues as to the exact nature of the immune defect.

Muckle–Wells syndrome (MWS), also known as urticaria-deafness-amyloidosis syndrome (UDA), is a rare autosomal dominant disease which causes sensorineural deafness and recurrent hives, and can lead to amyloidosis. Individuals with MWS often have episodic fever, chills, and joint pain. As a result, MWS is considered a type of periodic fever syndrome. MWS is caused by a defect in the CIAS1 gene which creates the protein cryopyrin. MWS is closely related to two other syndromes, familial cold urticaria and neonatal onset multisystem inflammatory disease—in fact, all three are related to mutations in the same gene and subsumed under the term cryopyrin-associated periodic syndromes (CAPS).

Hyperimmunoglobulinemia D with recurrent fever (HIDS) is a periodic fever syndrome originally described in 1984 by the internist Jos van der Meer, then at Leiden University Medical Centre. No more than 300 cases have been described worldwide.

Acute, tender, erythematous plaques, nodes, pseudovesicles and, occasionally, blisters with an annular or arciform pattern occur on the head, neck, legs, and arms, particularly the back of the hands and fingers. The trunk is rarely involved. Fever (50%); arthralgia or arthritis (62%); eye involvement, most frequently conjunctivitis or iridocyclitis (38%); and oral aphthae (13%) are associated features.

The chronic inflammation present in MWS over time can lead to deafness. In addition, the prolonged inflammation can lead to deposition of proteins in the kidney, a condition known as amyloidosis.

Sweet described a disease with four features: fever; leukocytosis; acute, tender, red plaques; and a dermal infiltrate of neutrophils. This led to the name acute febrile neutrophilic dermatosis. Larger series of patients showed that fever and neutrophilia are not consistently present. The diagnosis is based on the two constant features, a typical eruption and the characteristic histologic features; thus the eponym "Sweet's syndrome" is used.

Primary immunodeficiencies are disorders in which part of the body's immune system is missing or does not function normally. To be considered a "primary" immunodeficiency, the cause of the immune deficiency must not be secondary in nature (i.e., caused by other disease, drug treatment, or environmental exposure to toxins). Most primary immunodeficiencies are genetic disorders; the majority are diagnosed in children under the age of one, although milder forms may not be recognized until adulthood. While there are over 100 recognized PIDs, most are very rare. About 1 in 500 people in the United States are born with a primary immunodeficiency. Immune deficiencies can result in persistent or recurring infections, autoinflammatory disorders, tumors, and disorders of various organs. There are currently no cures for these conditions; treatment is palliative and consists of managing infections and boosting the immune system.

Periodic fever syndromes (also known as autoinflammatory diseases or autoinflammatory syndromes) are a set of disorders characterized by recurrent episodes of systemic and organ-specific inflammation. Unlike autoimmune disorders such as systemic lupus erythematosus, in which the disease is caused by abnormalities of the adaptive immune system, patients with autoinflammatory diseases do not produce autoantibodies or antigen-specific T or B cells. Instead, the autoinflammatory diseases are characterized by errors in the innate immune system.

The syndromes are diverse, but tend to cause episodes of fever, joint pains, skin rashes, abdominal pains and may lead to chronic complications such as amyloidosis.

Most autoinflammatory diseases are genetic and present during childhood. The most common genetic autoinflammatory syndrome is familial Mediterranean fever, which causes short episodes of fever, abdominal pain, serositis, lasting less than 72 hours. It is caused by mutations in the MEFV gene, which codes for the protein pyrin.

Pyrin is a protein normally present in the inflammasome. The mutated pyrin protein is thought to cause inappropriate activation of the inflammasome, leading to release of the pro-inflammatory cytokine IL-1β. Most other autoinflammatory diseases also cause disease by inappropriate release of IL-1β. Thus, IL-1β has become a common therapeutic target, and medications such as anakinra, rilonacept, and canakinumab have revolutionized the treatment of autoinflammatory diseases.

However, there are some autoinflammatory diseases that are not known to have a clear genetic cause. This includes PFAPA, which is the most common autoinflammatory disease seen in children, characterized by episodes of fever, aphthous stomatitis, pharyngitis, and cervical adenitis. Other autoinflammatory diseases that do not have clear genetic causes include adult-onset Still's disease, systemic-onset juvenile idiopathic arthritis, Schnitzler syndrome, and chronic recurrent multifocal osteomyelitis. It is likely that these diseases are multifactorial, with genes that make people susceptible to these diseases, but they require an additional environmental factor to trigger the disease.

Another example that shows that autoinflamatory conditions may not be genetic in origin is found in a report published in "Nature" which shows that diet is very important in the development of such diseases. The ingestion levels of highly saturated fats and cholesterol, (high fat diet, HFD) affects the microbiota composition of the gut. Changes in the microbiota induced by a HFD are protective against the susceptibility to develop osteomyelitis (autoimmune disease) as compared with the changes induced by a low-fat diet. The changes in the microbiome of individuals under HFD showed a reduction in "Prevotella" abundance and were accompanied by significantly reduced expression levels of pro-Interleukin-1β in distant neutrophils.

It is characterized by enlargement of the lymph nodes near the inner border of the lungs (called "hilar lymphadenopathy") as seen on x-ray, and tender red nodules (erythema nodosum) are classically present on the shins, predominantly in women. It may also be accompanied by arthritis (more prominent in men) and fever. The arthritis is often acute and involves the lower extremities.

Löfgren syndrome consists of the triad of erythema nodosum, bilateral hilar lymphadenopathy on chest radiograph, and arthralgia.

PAPA syndrome usually begins with arthritis at a young age, with the skin changes more prominent from the time of puberty.

The arthritis is the predominant feature, noted by its juvenile onset and destructive course. Individuals often recall episodes of arthritis precipitated by a traumatic event. With repeated episodes the joints become damaged with multiple joint replacements required. Hopefully, with improved treatment options, the damage will be limited in new cases.

Pyoderma gangrenosum is variably expressed, which means that it is not always present in all individuals with the disease. It presents as poorly healing ulcers with undermined edges. Pathergy is an important feature (this term refers to the tendency of ulcers to arise at points of injury). There are reports of lesions developing at the site of a joint replacement wound, central venous line and intravenous drip insertion.

Acne affects most individuals with PAPA syndrome but to a variable degree. It is usually of a severe nodulocystic type which if untreated results in scarring.

The syndrome is a rare clinical disorder.

- Physical

- Overgrowth

- Accelerated skeletal maturation

- Dysmorphic facial features

- Prominent eyes

- Bluish sclerae

- Coarse eyebrows

- Upturned nose

- Radiologic examination

- Accelerated osseous maturation

- Phalangeal abnormalities

- Tubular thinning of the long bones

- Skull abnormalities

- Mental

- Often associated with intellectual disability (of variable degree)

Paramyotonia congenita (PC), also known as paramyotonia congenita of von Eulenburg or Eulenburg disease, is a rare congenital autosomal dominant neuromuscular disorder characterized by “paradoxical” myotonia. This type of myotonia has been termed paradoxical because it becomes worse with exercise whereas classical myotonia, as seen in myotonia congenita, is alleviated by exercise. PC is also distinguished as it can be induced by cold temperatures. Although more typical of the periodic paralytic disorders, patients with PC may also have potassium-provoked paralysis. PC typically presents within the first decade of life and has 100% penetrance. Patients with this disorder commonly present with myotonia in the face or upper extremities. The lower extremities are generally less affected. While some other related disorders result in muscle atrophy, this is not normally the case with PC. This disease can also present as hyperkalemic periodic paralysis and there is debate as to whether the two disorders are actually distinct.

Patients typically complain of muscle stiffness that can continue to focal weakness. This muscle stiffness cannot be walked off, in contrast to myotonia congenita. These symptoms are increased (and sometimes induced) in cold environments. For example, some patients have reported that eating ice cream leads to a stiffening of the throat. For other patients, exercise consistently induces symptoms of myotonia or weakness. Typical presentations of this are during squatting or repetitive fist clenching. Some patients also indicate that specific foods are able to induce symptoms of paramyotonia congenita. Isolated cases have reported that carrots and watermelon are able to induce these symptoms. The canonical definition of this disorder precludes permanent weakness in the definition of this disorder. In practice, however, this has not been strictly adhered to in the literature.

AA-amyloidosis with kidney failure is a complication and may develop without overt crises. AA amyloid protein is produced in very large quantities during attacks, and at a low rate between them, and accumulates mainly in the kidney, as well as the heart, spleen, gastrointestinal tract, and thyroid.

There appears to be an increase in the risk for developing particular vasculitis-related diseases (e.g. Henoch–Schönlein purpura), spondylarthropathy, prolonged arthritis of certain joints and protracted myalgia.

There are seven types of attacks. Ninety percent of all patients have their first attack before they are 18 years old. All develop over 2–4 hours and last anywhere from 6 hours to 4 days. Most attacks involve fever.

1. Abdominal attacks, featuring abdominal pain, affect the whole abdomen with all signs of peritonitis (inflammation of abdominal lining), and acute abdominal pain like appendicitis. They occur in 95% of all patients and may lead to unnecessary laparotomy. Incomplete attacks, with local tenderness and normal blood tests, have been reported.

2. Joint attacks mainly occur in large joints, especially in the legs. Usually, only one joint is affected. 75% of all FMF patients experience joint attacks.

3. Chest attacks include pleuritis (inflammation of the pleura) and pericarditis (inflammation of the pericardium). Pleuritis occurs in 40% of patients and makes it difficult to breathe or lie flat, but pericarditis is rare.

4. Scrotal attacks due to inflammation of the tunica vaginalis occurs in up to 5% and may be mistaken for acute scrotum (i.e. testicular torsion).

5. Myalgia (rare in isolation)

6. Erysipeloid (a skin reaction on the legs, rare in isolation)

7. Fever without any of the other symptoms listed above (25%)

Blood tests show a high concentration of specific gamma-globulins (monoclonal gammopathy) of the IgM type. It almost always has light chains of the κ-type. A variant in which IgG is raised has been described, which appears to be ten times as rare. The immunoglobulins may show up in the urine as Bence Jones proteins. Signs of inflammation are often present: these include an increased white blood cell count (leukocytosis) and a raised erythrocyte sedimentation rate and C-reactive protein. There can be anemia of chronic disease. Bone abnormalities can be seen on radiological imaging (often increased density or osteosclerosis) or biopsy.

Because it is such a rare condition (as of September 2014, only 281 cases have been reported), it is important to rule out other conditions which can cause periodic fevers, paraproteins or chronic hives. These include (and are not limited to) autoimmune or autoinflammatory disorders such as adult-onset Still's disease, angioedema, hematological disorders such as lymphoma or monoclonal gammopathy of undetermined significance, other causes of hives, cryoglobulinemia, mastocytosis, chronic neonatal onset multisystem inflammatory disease or Muckle–Wells syndrome.

It is however possible to have more than one rare condition as seen by a patient with Schnitzler's syndrome and cold induced urticaria.

A meeting of experts, including Dr Liliane Schnitzler (then retired) took place in Strasbourg in May 2012 and drew up diagnostic criteria known as the "Strasbourg Criteria". These included two obligate criteria (chronic urticarial rash and monoclonal IgM or IgG) and several minor criteria; a definite diagnosis requires the two obligate criteria and two minor criteria if IgM, three if IgG; a probable diagnosis requires the two obligate criteria and one (IgM) or two (IgG) minor criteria.