Symptoms vary but they mostly involve skin disorders. The signs to look for include Raynaud's phenomenon, arthritis, myositis and scleroderma.

Visual symptoms include discoloring of the skin and painful swelling.

Scleroderma overlap syndrome: Scleroderma is a connective tissue disease that causes fibrosis and vascular abnormalities, but that also has an autoimmune component.

It is described by connective tissues complications. Blood testing includes screening for the positive antinuclear antibody.

Patients have symptoms of both systemic scleroderma and/or polymyositis and dermatomyositis.

1. Scleroderma: a group of rare diseases that involve the hardening and tightening of the skin and connective tissues

and/or:

Polymyositis: a rare inflammatory disease that causes muscle weakness affecting both sides of your body

Dermatomyositis: an inflammatory disease of skin and muscle marked especially by muscular weakness and skin rash.

The disease typically presents with joint pain, high fevers, a salmon-pink rash, enlargement of the liver and spleen, swollen lymph nodes, and an increased white blood cell count in the blood. Tests for rheumatoid factor and anti-nuclear antibodies are usually negative and serum ferritin is elevated. Patients experiencing a flare-up from Adult-onset Still's disease usually report extreme fatigue, swelling of the lymph nodes and, less commonly, fluid accumulation in the lungs and heart. In rare cases, AOSD can cause aseptic meningitis and sensorineural hearing loss.

Adult-onset Still's disease (AOSD) is a form of Still's disease, a rare systemic autoinflammatory disease characterized by the classic triad of persistent high spiking fevers, joint pain, and a distinctive salmon-colored bumpy rash. The disease is considered a diagnosis of exclusion. Levels of the iron-binding protein ferritin may be elevated with this disorder. AOSD may present in a similar manner to other inflammatory diseases and to autoimmune diseases, which must be ruled out before making the diagnosis.

Prognosis is usually favorable but manifestations of the disease affecting the lungs, heart, or kidneys may occasionally cause severe life-threatening complications. It is treated first with steroids such as prednisone. Drugs that block the action of interleukin-1, such as anakinra, can be effective treatments when standard steroid treatments are insufficient.

The signs and symptoms of Kikuchi disease are fever, enlargement of the lymph nodes (lymphadenopathy), skin rashes, and headache. Rarely, enlargement of the liver and spleen and nervous system involvement resembling meningitis are seen. Often a bout of extreme fatigue can occur - often taking hold during latter parts of the day and the affected person can be more prone to fatigue from exercise.

Kikuchi disease or Kikuchi-Fujimoto disease was described in 1972 in Japan. It is also known as histiocytic necrotizing lymphadenitis, Kikuchi necrotizing lymphadenitis, phagocytic necrotizing lymphadenitis, subacute necrotizing lymphadenitis, and necrotizing lymphadenitis.

It was first described by Dr Masahiro Kikuchi (1935–2012) in 1972 and independently by Y. Fujimoto.

The three major types of JIA are oligoarticular, polyarticular, and systemic.

Symptoms of JIA are often nonspecific initially, and include lethargy, reduced physical activity, and poor appetite. The first manifestation, particularly in young children, may be limping. Children may also become quite ill, presenting with flu-like symptoms that persist. The cardinal clinical feature is persistent swelling of the affected joint(s), which commonly include the knee, ankle, wrist, and small joints of the hands and feet. Swelling may be difficult to detect clinically, especially for joints such as those of the spine, sacroiliac joints, shoulder, hip, and jaw, where imaging techniques such as ultrasound or MRI are very useful.

Pain is an important symptom. Morning stiffness that improves later in the day is a common feature (this implies inflammatory-type joint pain versus mechanical-type joint pain). Late effects of arthritis include joint contracture (stiff, bent joint due to fibrosis) and joint damage. Children with JIA vary in the degree to which they are affected by particular symptoms. Symptoms may also differ between sexes, affecting girls and boys differently among different geographic locations. This is predicted to be due to biological differences in different geographic regions. Children may also have swollen joints (inflammatory swelling, or in chronic arthritis due to synovial proliferation and thickening, and periarticular soft-tissue swelling).

RS3PE is a constellation of symptoms that can be caused by many other conditions. Since there is no definitive diagnostic test, other conditions have to be ruled out before this rare condition can be diagnosed.

The main differential diagnosis is polymyalgia rheumatica (PMR), although pain, stiffness and weakness at the level of the shoulders and pelvic girdle with associated systemic symptoms (fever, malaise, fatigue, weight loss) is more typical of PMR. Prospective studies have found a subgroup of PMR patients with hand edema, as well as other similarities. Thus, RS3PE has been proposed as a condition related to PMR or even that they are both part of the same disorder. However, PMR typically requires protracted courses of steroids, whereas corticosteroids can be tapered more quickly with persisting remission in RS3PE.

Other rheumatological disorders that can cause the features typical for RS3PE include late onset (seronegative) rheumatoid arthritis, acute sarcoidosis, ankylosing spondylitis and other spondyloarthropathies such as psoriatic arthropathy, mixed connective tissue disease, chondrocalcinosis and arthropathy due to amyloidosis.

RS3PE has been documented in patients with cancers (Non-Hodgkin's lymphoma, gastric cancer, pancreatic cancer, lung cancer, breast cancer, colon cancer, prostate cancer and bladder cancer, among others), in whom it might represent a paraneoplastic manifestation.

Other underlying disorders include vasculitides such as polyarteritis nodosa.

Other causes of edema include heart failure, hypoalbuminemia, nephrotic syndrome and venous stasis. The key distinguishing feature is that these conditions don't tend to manifest with pitting edema at the back of the hands.

Individuals affected by RS3PE typically have repeated episodes of inflammation of the lining of their synovial joints and swelling of the end portion of the limbs. The arms and hands are more commonly affected than the legs and feet. Both sides are usually involved though RS3PE can affect only one side in certain cases.

Signs and symptoms of the disease include diarrhea, nausea, swelling of the legs, protein-losing enteropathy, immunodeficiency and loss of lymphatic fluid into the intestines. It is usually diagnosed before the patient is 3 years old, but it is sometimes diagnosed in adults.

The illness is usually caused by lymphatic vessels that were misshaped at birth, causing obstruction and subsequent enlargement. The condition can also be a result of other illnesses such as constrictive pericarditis and pancreatitis. The disease is diagnosed by doing a biopsy of the affected area. Severity of the disease is then determined by measuring alpha-antitrypsin proteins in a stool sample.

LCH provokes a non-specific inflammatory response, which includes fever, lethargy, and weight loss. Organ involvement can also cause more specific symptoms.

- Bone: The most-frequently seen symptom in both unifocal and multifocal disease is painful bone swelling. The skull is most frequently affected, followed by the long bones of the upper extremities and flat bones. Infiltration in hands and feet is unusual. Osteolytic lesions can lead to pathological fractures.

- Skin: Commonly seen are a rash which varies from scaly erythematous lesions to red papules pronounced in intertriginous areas. Up to 80% of LCH patients have extensive eruptions on the scalp.

- Bone marrow: Pancytopenia with superadded infection usually implies a poor prognosis. Anemia can be due to a number of factors and does not necessarily imply bone marrow infiltration.

- Lymph node: Enlargement of the liver in 20%, spleen in 30% and lymph nodes in 50% of Histiocytosis cases.

- Endocrine glands: Hypothalamic pituitary axis commonly involved. Diabetes insipidus is most common. Anterior pituitary hormone deficiency is usually permanent.

- Lungs: some patients are asymptomatic, diagnosed incidentally because of lung nodules on radiographs; others suffer from chronic cough and shortness of breath.

- Less frequently gastrointestinal tract, central nervous system, and oral cavity.

A rare disease is any disease that affects a small percentage of the population. In some parts of the world, an orphan disease is a rare disease whose rarity means there's a lack of a market large enough to gain support and resources for discovering treatments for it, except by the government granting economically advantageous conditions to creating and selling such treatments. Orphan drugs are ones so created or sold.

Most rare diseases are genetic, and thus are present throughout the person's entire life, even if symptoms do not immediately appear. Many rare diseases appear early in life, and about 30 percent of children with rare diseases will die before reaching their fifth birthday. With a single diagnosed patient only, ribose-5-phosphate isomerase deficiency is considered the rarest genetic disease.

No single cutoff number has been agreed upon for which a disease is considered rare. A disease may be considered rare in one part of the world, or in a particular group of people, but still be common in another.

Global Genes have estimated that more than 300 million people worldwide are living with one of the 7,000 diseases they define as "rare" in the United States.

Seen mostly in children, multifocal unisystem LCH is characterized by fever, bone lesions and diffuse eruptions, usually on the scalp and in the ear canals. 50% of cases involve the pituitary stalk, leading to diabetes insipidus. The triad of diabetes insipidus, exopthalmos, and lytic bone lesions is known as the "Hand-Schüller-Christian triad". Peak onset is 2–10 years of age.

Symptoms are not specific; most patients report itching, burning, and soreness. A small subset of patients may be asymptomatic. Presence of vulvar pain, bleeding, and tumor formation are reported to be more common in patients affected by invasive disease.Signs and symptoms are skin lesions, often mistaken as eczema, that may be itchy or painful.

Hughes–Stovin syndrome is a rare autoimmune disorder of unknown cause that is characterized by the combination of multiple pulmonary artery aneurysms and deep vein thrombosis. It is named after the two British physicians, John Patterson Hughes and Peter George Ingle Stovin, who first described it in 1959. It is a rare variant of Behçet's disease, which entails more general problems with the circulatory system. Most patients are young adult males between the age of 20-40.

Common clinical presentations include fever, cough, dyspnea and hemoptysis. Radiological features are similar to those of Behçet's disease. There is no satisfactory treatment for this disease.

Vulvar Paget disease presents as a variety of clinical lesions that may occur over a protracted course. Initially it is velvety, soft, and red or bright pink with scattered white islands of hyperkeratosis. (a strawberry and cream appearance) The lesions become erythematous, plaque like, and desquamating especially when located in dry areas. Rarely the appearance is ulcerated. The borders appear irregular, slightly elevated, and sharply demarcated. The visible borders of vulvar Paget disease are often misleading as Paget cells may spread along the basal layers of normal appearing skin with multicentric foci. Involvement may be extensive including the perianal region, genitocrural, and inguinal folds. Clinical examination should determine the presence of periurethral and perianal lesions. In these cases an involvement of the skin by a noncutaneous internal neoplasm may occur.

Patients usually complain of pain in one joint, which persists for months, or even years, does not ease with exercise, steroid injection or heat treatment, shows nothing on X-ray, but shows a definite restriction of movement.

There are 3 defined stages to this disease:

- early: no loose bodies but active synovial disease;

- transitional: active synovial disease, and loose bodies;

- late: loose bodies but no synovial disease;

In the early stages of the disease it is often confused with tendinitis and/or arthritis. Once it reaches transitional the loose bodies become apparent with X-ray in greater than 70% of cases, with MRI often showing where xray fails. In experienced hands, US is also useful for the diagnosis.

In the disease, the thin flexible membrane of the synovium gradually forms blisters which calcify and enlarge. These nodules eventually break free and float around the joint space becoming larger – these add to the discomfort and stiffness of the joint.

The disease is rare and little known and there is currently no known cure. The affected tissue will show up as a semi-solid mass in a MRI scan, final diagnosis is usually confirmed by taking a biopsy.

Synovial chondromatosis occurs twice as commonly in males as females and usually in their forties. However, online communities for synovial chondromatosis patients have yielded a stark contrast, with equal representation from both genders and members diagnosed as young as late teenage/early 20s.

The disease generally affects only one of the larger weight bearing joints (hip, ankle, knee) – although the elbow, and wrist can also be affected. Rarely involves the temporal mandibular joint.

Rheumatism or rheumatic disorder is an umbrella term for conditions causing

chronic, often intermittent pain affecting the joints and/or connective tissue.

The study of, and therapeutic interventions in, such disorders is called rheumatology.

The term "rheumatism", however, does not designate any specific disorder, but covers at least 200 different conditions.

Sources dealing with rheumatism tend to focus on arthritis, but "rheumatism" may also refer to other conditions causing chronic pain, grouped as "non-articular rheumatism", also known as "regional pain syndrome" or "soft tissue rheumatism". The term "Rheumatic Diseases" is used in MeSH to refer to connective tissue disorders.

Synovial chondromatosis (synonyms include synovial osteochondromatosis, primary synovial osteochondromatosis, and synovial chondrometaplasia) is a disease affecting the synovium, a thin flexible membrane around a joint. It is also known as Reichel's syndrome or Reichel-Jones-Henderson syndrome, named after Friedrich Paul Reichel, Hugh Toland Jones and Melvin Starkey Henderson.

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.

It is a genetic developmental disorder with clinical diversity characterized by hypoparathyroidism, sensorineural deafness and renal disease. Patients usually present with hypocalcaemia, tetany, or afebrile convulsions at any age. Hearing loss is usually bilateral and may range from mild to profound impairment. Renal disease includes nephrotic syndrome, cystic kidney, renal dysplasia, hypoplasia or aplasia, pelvicalyceal deformity, vesicoureteral reflux, chronic kidney disease, hematuria, proteinuria and renal scarring.

Many rheumatic disorders of chronic, intermittent joint pain have historically been caused by infectious diseases. Their etiology was unknown until the 20th century and not treatable, like Lyme disease (in the Northern and Northeastern US), coccidiomycosis or Valley fever (in the Western US), and Chikungunya in India and a myriad of causes for postinfectious arthritis also known as reactive arthritis like, for example, the once very common rheumatic fever after Group A Streptococcus infection up to the rare Whipple's disease.

Major rheumatic disorders currently recognized include

- Back pain

- Bursitis/Tendinitis of the shoulder, wrist, biceps, leg, knee cap (patella), ankle, hip, and Achilles tendon

- Capsulitis

- Neck pain

- Osteoarthritis

- Palindromic rheumatism has been theorized to be a form of rheumatoid arthritis.

Although these disorders probably have little in common in terms of their epidemiology, they do share three characteristics: they cause chronic, often intermittent pain, they are difficult to treat and are collectively very common.

Rheumatic diseases caused by autoimmunity include:

- Ankylosing spondylitis

- relapsing polychondritis

- systemic lupus erythematosus

- rheumatoid arthritis

- gout, inflammatory arthritis, pseudogout

- juvenile arthritis

- Sjögren syndrome

- scleroderma

- Polymyositis

- Dermatomyositis

- Behçet's disease

- Psoriatic arthritis

The disease causes numerous whitish punctiform papules and brownish macules arranged in a necklace-like pattern.