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.

Repeated, periodic joint effusions of the knee. Usually one knee is affected but sometimes both knees. Other joints may also be involved along with the knee. Effusions are large, restricting range of motion but significant pain is not a feature. There is usually stiffness. Tenderness of the joint may or may not be present. Aspirated synovial fluid is usually sterile but will sometimes show elevated cell count (>100 cells/mL) with 50% being polymorphonuclear leukocytes.

Onset of effusions are sudden with no particular trigger or stimulus. Each episode lasts for a few days to about a week and recurs in cycles of 7 to 11 days with extremes of 3 days to 30 days also reported. Sometimes the joint may begin to swell again as soon as the fluid has subsided. Where both knees are affected concurrently, as one joint ceases to swell the other may become involved.

The cycle of joints swellings have been reported as being very regular, even predictable. This has been a characteristic feature of IH in many case reports. However, over the longer-term especially, these cycles of effusion and recovery may not be as constant as first reported.

In women, many cases seem to begin at puberty. Episodes of knee swelling may coincide the menstrual cycle. In nearly all case reports, pregnancy seems to suppress the condition but after birth, during lactation, it returns.

In the main, patients are mostly free of other symptoms. Fever is rare. There no signs of local inflammation or lymphatic involvement. Laboratory tests are generally normal or within reference limits.

Sufferers experience pain and swelling in the middle part of the foot and usually limp as a result. Patients that walk with a limp tend to walk with increased weight on the lateral side of the foot. Also, there can be tenderness over the navicular. Patients often complain of pain over the apex.

An X-ray of both feet is used to diagnose disease. The affected foot tends to have a sclerotic and flattened navicular bone.

Fibrous dysplasia is a mosaic disease that can involve any part or combination of the craniofacial, axillary, and/or appendicular skeleton. The type and severity of the complications therefore depend on the location and extent of the affected skeleton. The clinical spectrum is very broad, ranging from an isolated, asymptomatic monostotic lesion discovered incidentally, to severe disabling disease involving practically the entire skeleton and leading to loss of vision, hearing, and/or mobility.

Individual bone lesions typically manifest during the first few years of life and expand during childhood. The vast majority of clinically significant bone lesions are detectable by age 10 years, with few new and almost no clinically significant bone lesions appearing after age 15 years. Total body scintigraphy is useful to identify and determine the extent of bone lesions, and should be performed in all patients with suspected fibrous dysplasia.

Children with fibrous dysplasia in the appendicular skeleton typically present with limp, pain, and/or pathologic fractures. Frequent fractures and progressive deformity may lead to difficulties with ambulation and impaired mobility. In the craniofacial skeleton, fibrous dysplasia may present as a painless “lump” or facial asymmetry. Expansion of craniofacial lesions may lead to progressive facial deformity. In rare cases patients may develop vision and/or hearing loss due to compromise of the optic nerves and/or auditory canals, which is more common in patients with McCune-Albright syndrome associated growth hormone excess. Fibrous dysplasia commonly involves the spine, and may lead to scoliosis, which in rare instances may be severe. Untreated, progressive scoliosis is one of the few features of fibrous dysplasia that can lead to early fatality.

Bone pain is a common complication of fibrous dysplasia. It may present at any age, but most commonly develops during adolescence and progresses into adulthood.

Bone marrow stromal cells in fibrous dysplasia produce excess amounts of the phosphate-regulating hormone fibroblast growth factor-23 (FGF23), leading to loss of phosphate in the urine. Patients with hypophosphatemia may develop rickets/osteomalacia, increased fractures, and bone pain.

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

- Episodic fever

- Erythrocyte sedimentation rate(increased)

- Pericarditis

- Splenomegaly

- Uveitis

- Vertigo

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%)

Intermittent hydrarthrosis (IH), also known as "periodic synoviosis", "periodic benign synovitis", or "periodic hydrarthritis", is a chronic condition of unknown cause characterized by recurring, temporary episodes of fluid accumulation in the knee. While the knee is mainly involved, occasionally other joints such as the elbow or ankle can additionally be affected. Fluid accumulation in the joint can be extensive causing discomfort and impairing movement, although affected joints are not usually very painful. While the condition is chronic, it does not appear to progress to more destructive damage of the joint. It seems to affect slightly more women than men.

Episodes of swelling last several days or longer, can occur with regular or semi-regular frequency, typically one or two episodes per month. Between periods of effusion, knee swelling reduces dramatically providing largely symptomless intervals. Unlike some other rheumatological conditions such as rheumatoid arthritis, laboratory findings are usually within normal ranges or limits.

Clear treatment options have yet to be established. NSAIDs and COX2-inhibitors are generally not effective. Where this condition has been correctly diagnosed, various anti-rheumatic drugs as well as colchicine may be trialled to find the most effective option. More aggressive intra-articular treatment such chemical or radio-active synovectomy can also be helpful although benefits beyond 1 year have not been reported in literature.

Due to its inflammatory nature, its recurrent outbreaks, and its lack of any known pathogen, CRMO has been reclassified as an autoinflammatory disease. This particular classification encompasses both hereditary types (familial Mediterranean fever, mevalonate kinase deficiency, TNF receptor associated periodic syndrome, cryopyrin-associated periodic syndrome, Blau syndrome, pyogenic sterile arthritis, pyoderma gangrenosum and acne syndrome, CRMO) and multifactorial disorders (Crohn's and Behçet's diseases). CRMO is no longer considered an autoimmune but rather an inherited, autoinflammatory disease.

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.

Köhler disease (also spelled "Kohler" and referred to in some texts as Kohler disease I) is a rare bone disorder of the foot found in children between six and nine years of age. The disease typically affects boys, but it can also affect girls. It was first described in 1908 by Alban Köhler (1874–1947), a German radiologist.

It is caused when the navicular bone temporarily loses its blood supply. As a result, tissue in the bone dies and the bone collapses. When treated, it causes no long term problems in most cases although rarely can return in adults. As the navicular bone gets back to normal, symptoms typically abate.

In February 2010, the "Journal of the American Medical Association" reported that the 19-year-old king Tutankhamun may well have died of complications from malaria combined with Köhler disease II.

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.

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.

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).

Other symptoms of the syndrome include:

- retroorbital pain due to pain in the area supplied by the ophthalmic branch of the trigeminal nerve (fifth cranial nerve),

- abducens nerve palsy (sixth cranial nerve), and

- otitis media.

Other symptoms can include photophobia, excessive lacrimation, fever, and reduced corneal sensitivity.

The syndrome is usually caused by the spread of an infection into the petrous apex of the temporal bone.

Fibrous dysplasia is a disorder where normal bone and marrow is replaced with fibrous tissue, resulting in formation of bone that is weak and prone to expansion. As a result, most complications result from fracture, deformity, functional impairment, and pain. Disease occurs along a broad clinical spectrum ranging from asymptomatic, incidental lesions to severe disabling disease. Disease can affect one bone (monostotic) or multiple (polyostotic), and may occur in isolation or in combination with cafe-au-lait skin macules and hyperfunctioning endocrinopathies, termed McCune-Albright syndrome. More rarely, fibrous dysplasia may be associated with intramuscular myxomas, termed Mazabraud's syndrome. Fibrous dysplasia is very rare, and there is no known cure. Fibrous dysplasia is not a form of cancer.

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.

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.

Panner disease is an osteochondrosis of the capitellum of the elbow. Panner disease is primarily seen in boys between the ages of five and ten years old. Panner disease is often caused by excessive throwing due to valgus stress. The disease causes pain and stiffness in the affected elbow and may limit extension; the affected elbow is usually on the dominant arm the child uses. The disease may be associated with pitching and athletic activity. On radiographs, the capitellum may appear irregular with areas of radiolucency. Treatment is symptomatic, with a good prognosis. Treatment is minimal and includes restricting athletic activity to allow for the elbow to heal and for pain to be relieved. The disease is named after the Danish radiologist Hans Jessen Panner (1871–1930).

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).

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.

An individual with Panner disease most commonly experiences elbow pain near the capitellum. Other symptoms include:

- Stiffness in the elbow

- Elbow swelling

- Limited range of motion

- Elbow extension limitation

- Tenderness

These symptoms worsen with physical activity such a throwing a ball or gymnastics for example. The symptoms begin unexpectedly and are often present for several days or weeks, and the symptoms tend to last even longer.

The definitive symptom of ONJ is the exposure of mandibular or maxillary bone through lesions in the gingiva that do not heal. Pain, inflammation of the surrounding soft tissue, secondary infection or drainage may or may not be present. The development of lesions is most frequent after invasive dental procedures, such as extractions, and is also known to occur spontaneously. There may be no symptoms for weeks or months, until lesions with exposed bone appear. Lesions are more common on the mandible than the maxilla.

- Pain and neuropathy

- Erythema and suppuration

- Bad breath

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)

Gradenigo's syndrome, also called Gradenigo-Lannois syndrome and petrous apicitis, is a complication of otitis media and mastoiditis involving the apex of the petrous temporal bone. It was first described by Giuseppe Gradenigo in 1904 when he reported a triad of symptoms consisting of: (1)"unilateral periorbital pain" related to trigeminal nerve involvement, (2)"diplopia" due to sixth nerve palsy and (3)persistent "otorrhea", associated with bacterial otitis media with apex involvement of the petrous part of the temporal bone (petrositis). The classical syndrome related to otitis media has become very rare after the antibiotic era.

Characterized by being less than 1.5 cm in diameter, osteoid osteomas most frequently occur in young men (Male:Female ratio 3:1) and may occur in any bone of the body, most frequently around the knee but often also seen in the vertebrae, in the long bones and less commonly in the mandible or other craniofacial bones.

Severe pain typically occurs at night, but can also be constant at any time of day. The chief complaint may only be of dull pain which is non radiating and persistent throughout 24 hours but increases significantly at night. Pain tends to be relieved with NSAIDs such as ibuprofen.