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 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.

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.

PAPA syndrome is an acronym for pyogenic arthritis, pyoderma gangrenosum and acne. It is a rare genetic disorder characterised by its effects on skin and joints.

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.

SAPHO syndrome includes a variety of inflammatory bone disorders that may be associated with skin changes. These diseases share some clinical, radiologic, and pathologic characteristics.

An entity initially known as chronic recurrent multifocal osteomyelitis (CRMO) was first described in 1972. Subsequently, in 1978, several cases of CRMO were associated with blisters on the palms and soles (palmoplantar pustulosis). Since then, a number of associations between skin conditions and osteoarticular disorders have been reported under a variety of names, including sternocostoclavicular hyperostosis, pustulotic arthro-osteitis, and acne-associated spondyloarthropathy. The term SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) was coined in 1987 to represent this spectrum of inflammatory bone disorders that may or may not be associated with dermatologic pathology.

The definition is Synovitis Acne (commonly involving the face and upper back) Pustulosis Hyperostosis Osteitis

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.

Relapsing polychondritis may affect many different organ systems of the body. At first, some people with the disease may have only nonspecific symptoms such as fever, weight loss, and malaise.

Peripheral arthritis has been reported in 92% of cases of SAPHO as well.

In children, the SAPHO syndrome is most likely to affect the metaphysis of long bones in the legs (tibia, femur, fibula), followed by clavicles and spine.

Inflammation occurs in the laryngeal, tracheal and bronchial cartilages. Both of these sites are involved in 10% of persons with RP at presentation and 50% over the course of this autoimmune disease, and is more common among females.

The involvement of the laryngotracheobronchial cartilages may be severe and life-threatening; it causes one-third of all deaths among persons with RP.

Laryngeal chondritis is manifested as pain above the thyroid gland and, more importantly, as dysphonia with a hoarse voice or transient aphonia. Because this disease is relapsing, recurrent laryngeal inflammation may result in laryngomalacia or permanent laryngeal stenosis with inspiratory dyspnea that may require emergency tracheotomy as a temporary or permanent measure.

Tracheobronchial involvement may or may not be accompanied with laryngeal chondritis and is potentially the most severe manifestation of RP.

The symptoms consist of dyspnea, wheezing, a nonproductive cough, and recurrent, sometimes severe, lower respiratory tract infections.

Obstructive respiratory failure may develop as the result of either permanent tracheal or bronchial narrowing or chondromalacia with expiratory collapse of the tracheobronchial tree. Endoscopy, intubation, or tracheotomy has been shown to hasten death.

Chronic recurrent multifocal osteomyelitis (CRMO) ("multifocal" because it can erupt in different sites, primarily bones; "osteomyelitis" because it is very similar to that disease but appears to be without any infection), also known as chronic recurring multifocal osteomyelitis, is a rare condition (1:1,000,000), in which the bones have lesions, inflammation, and pain. Its definition is evolving. Many doctors and articles described CRMO as an autoimmune disease that has symptoms similar to osteomyelitis, but without the infection. Some doctors thought CRMO was related to SAPHO syndrome. Research now classifies CRMO as an inherited autoinflammatory disease but have yet to isolate the exact gene responsible for it. Some specialists believe they have discovered a link between CRMO with a rare allele of marker D18S60, resulting in a haplotype relative risk (HRR) of 18. Other experts found that "mutations in LPIN2 cause a syndromic form of chronic recurrent multifocal osteomyelitis known as Majeed syndrome, while mutations in pstpip2 cause a murine form of the disorder. The roles played by LPIN2 and the human homolog of pstpip2, PSTPIP2, in the cause of chronic recurrent multifocal osteomyelitis are uncertain. The professional theories seem to be moving in the direction of an inherited gene.

LRBA deficiency presents as a syndrome of autoimmunity, lymphoproliferation, and humoral immune deficiency. Predominant clinical problems include idiopathic thrombocytopenic purpura (ITP), autoimmune hemolytic anemia (AIHA), and an autoimmune enteropathy. Before the discovery of these gene mutations, patients were diagnosed with common variable immune deficiency (CVID), which is characterized by low antibody levels and recurrent infections. Infections mostly affect the respiratory tract, as many patients suffer from chronic lung disease, pneumonias, and bronchiectasis. Lymphocytic interstitial lung disease (ILD) is also observed, which complicates breathing and leads to impairment of lung function and mortality. Infections can also occur at other sites, such as the eyes, skin and gastrointestinal tract. Many patients suffer from chronic diarrhea and inflammatory bowel disease. Other clinical features can include hepatosplenomegaly, reoccurring warts, growth retardation, allergic dermatitis, and arthritis. Notably, LRBA deficiency has also been associated with type 1 diabetes mellitus. There is significant clinical phenotypic overlap with disease caused by CTLA4 haploinsufficiency. Since LRBA loss results in a loss of CTLA4 protein, the immune dysregulation syndrome of LRBA deficient patients can be attributed to the secondary loss of CTLA4. Because the predominant features of the disease include autoantibody-mediated disease (AIHA, ITP), Treg defects (resembling those found in CTLA4 haploinsufficient patients), autoimmune infiltration (of non-lymphoid organs, also resembling that found in CTLA4 haploinsufficient patients), and enteropathy, the disease has been termed LATAIE for LRBA deficiency with autoantibodies, Treg defects, autoimmune infiltration, and enteropathy.

CRMO/CNO is a diagnosis of exclusion. This means that other diseases must be ruled out before the diagnosis can be made. Generally, many tests are required, such as blood tests, x-rays, bone scans, MRI and often a bone biopsy.

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).

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.

LRBA deficiency is a rare genetic disorder of the immune system. This disorder is caused by a mutation in the gene "LRBA". LRBA stands for “Lipopolysaccharide (LPS)-responsive vesicle trafficking, beach- and anchor-containing” gene. This condition is characterized by autoimmunity, lymphoproliferation, and immune deficiency. It was first described by Gabriela Lopez-Herrera from University College London in 2012. Investigators in the laboratory of Dr. Michael Lenardo at National Institute of Allergy and Infectious Diseases, the National Institutes of Health and Dr. Michael Jordan at Cincinnati Children’s Hospital Medical Center later described this condition and therapy in 2015.

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.

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).

Hidradenitis suppurativa is a chronic inflammatory skin condition, considered a member of the acne family of disorders. It is sometimes called acne inversa. The first signs of HS are small bumps on the skin that resemble pimples, cysts, boils, or folliculitis. As the disease progresses and abscesses reoccur, they become larger and more painful; eventually tunnels of scar tissue connect the lesions. These lesions may open up if they become too enlarged and drain bloodstained pus. One risk factor is age; HS usually first appears during the 20s and early 30s. The condition is much more common in women than in men but is usually more serious and debilitating in men. Other associated conditions include obesity, diabetes, metabolic syndrome, arthritis, acne, and other inflammatory disorders. Early diagnosis of this disease is very important to decrease the number of flares, pain, and discomfort.

Barraquer–Simons syndrome (or acquired partial lipodystrophy, cephalothoracic lipodystrophy, and progressive lipodystrophy)) is a rare form of lipodystrophy,

which usually first affects the head, and then spreads to the thorax.

It is named for Luis Barraquer Roviralta (1855–1928), a Spanish physician, and Arthur Simons (1879–1942), a German physician. Some evidence links it to "LMNB2".

Estimating the mortality rate based on the available literature is difficult. Several case reports have revealed an association between acquired partial lipodystrophy and other diseases.

Nephropathy, in the form of membranoproliferative glomerulonephritis, occurs in about 20% of patients. Usually, patients do not have clinically evident renal disease or abnormalities in renal function until they have had the disease for 8 or more years. Membranoproliferative glomerulonephritis usually presents with asymptomatic proteinuria or hematuria.

The disease may gradually progress. About 40-50% of patients develop end-stage renal disease over the course of 10 years. This condition is responsible for most recurrent hospital admissions in patients with acquired partial lipodystrophy. Rapid progression of renal disease in a pregnant patient was reported. Recurrent disease in transplanted kidneys is common, although there have been reports of successful transplantations.

Associated autoimmune diseases (e.g., systemic lupus erythematosus, thyroiditis) contribute significantly to increased morbidity in these patients compared with the general population. Although uncommon, insulin resistance increases cardiovascular risk. Susceptibility to bacterial infections probably results from a C3 deficiency (due to complement activation and consumption of C3). Low C3 levels may impair complement-mediated phagocytosis and bacterial killing.

A rare autoimmune disease characterized by recurrent urticaria (nettle rash), first described in the 1970s. There is no defined paradigm for the syndrome aetiology and severity in progression. Diagnosis is confirmed with the identification of at least two conditions from: venulitis on skin biopsy, arthritis, ocular inflammation, abdominal pain or positive C1q antibodies to immune complexes. It is this last category, anti-C1q antibodies, that all HUV patients test positive for. "In vitro" experiments and mouse models of the disease have not thoroughly determined the link between these antibodies and the disease, even though the link is so pronounced.

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.

Serositis is seen in numerous conditions:

- Lupus erythematosus (SLE), for which it is one of the criteria,

- Rheumatoid arthritis

- Familial Mediterranean fever (FMF)

- Chronic renal failure

- Juvenile idiopathic arthritis

- Inflammatory bowel disease (especially Crohn's disease)

- Acute appendicitis

- Diffuse cutaneous systemic sclerosis

Livedo reticularis is a common skin finding consisting of a mottled reticulated vascular pattern that appears as a lace-like purplish discoloration of the skin. The discoloration is caused by swelling of the venules owing to obstruction of capillaries by small blood clots. The blood clots in the small blood vessels can be a secondary effect of a condition that increases a person's risk of forming blood clots, including a wide array of pathological and nonpathological conditions . Examples include hyperlipidemia, microvascular hematological or anemia states, nutritional deficiencies, hyper- and autoimmune diseases, and drugs/toxins.

The condition may be normal or related to more severe underlying pathology. Its differential diagnosis is broadly divided into possible blood diseases, autoimmune (rheumatologic) diseases, cardiovascular diseases, cancers, and endocrine disorders. It can usually (in 80% of cases) be diagnosed by biopsy.

It may be aggravated by exposure to cold, and occurs most often in the lower extremities.

The condition's name derives from the Latin "livere" meaning bluish and "reticular" which refers to the net-like appearance.