As many as 70% of people with lupus have some skin symptoms. The three main categories of lesions are chronic cutaneous (discoid) lupus, subacute cutaneous lupus, and acute cutaneous lupus. People with discoid lupus may exhibit thick, red scaly patches on the skin. Similarly, subacute cutaneous lupus manifests as red, scaly patches of skin but with distinct edges. Acute cutaneous lupus manifests as a rash. Some have the classic malar rash (or "butterfly rash") associated with the disease. This rash occurs in 30 to 60% of people with SLE.

Hair loss, mouth and nasal ulcers, and lesions on the skin are other possible manifestations.

The most commonly sought medical attention is for joint pain, with the small joints of the hand and wrist usually affected, although all joints are at risk. More than 90 percent of those affected will experience joint and/or muscle pain at some time during the course of their illness. Unlike rheumatoid arthritis, lupus arthritis is less disabling and usually does not cause severe destruction of the joints. Fewer than ten percent of people with lupus arthritis will develop deformities of the hands and feet. People with SLE are at particular risk of developing osteoarticular tuberculosis.

A possible association between rheumatoid arthritis and SLE has been suggested, and SLE may be associated with an increased risk of bone fractures in relatively young women.

Symptoms vary from person to person, and may come and go. Almost everyone with lupus has joint pain and swelling. Some develop arthritis. Frequently affected joints are the fingers, hands, wrists, and knees.

Other common symptoms include:

- chest pain during respiration

- joint pain

- oral ulcer

- fatigue

- fever with no other cause

- general discomfort, uneasiness, or ill feeling (malaise)

- hair loss

- sensitivity to sunlight

- skin rash – a "butterfly" rash in about half people with SLE

- swollen lymph nodes

Lupus erythematosus is a name given to a collection of autoimmune diseases in which the human immune system becomes hyperactive and attacks healthy tissues. Symptoms of these diseases can affect many different body systems, including joints, skin, kidneys, blood cells, heart, and lungs. The most common and severe form is systemic lupus erythematosus.

Signs and symptoms of drug-induced lupus erythematosus include the following:

- Joint pain (arthralgia) and muscle pain (myalgia)

- Fatigue

- Serositis —inflammation of the tissues lining the heart and lungs.

- Anti-histone antibodies in 95% of cases

These signs and symptoms are not side effects of the drugs taken which occur during short term use. DIL occurs over long-term and chronic use of the medications listed below. While these symptoms are similar to those of systemic lupus erythematosus, they are generally not as severe unless they are ignored which leads to more harsh symptoms, and in some reported cases, death.

Disease presentation varies widely from patient to patient, as UCTD is by definition nonspecific. Symptoms typically include constitutional complaints that are common to connective tissue diseases such as fatigue, a general sense of feeling unwell, and fever.

Other symptoms associated with UCTD include:

- dry eyes

- dry mouth

- hair loss

- joint inflammation

- joint pain

- oral ulcers

- positive ANA test

- raynaud's phenomenon

- sun sensitive rash

Lung involvement, such as nonspecific interstitial pneumonia, is a possible disease complication.

Drug-induced lupus erythematosus (DIL or DILE) is an autoimmune disorder (similar to systemic lupus erythematosus [SLE]) caused by chronic use of certain drugs. These drugs cause an autoimmune response (the body attacks its own cells) producing symptoms similar to those of SLE. There are 38 known medications to cause DIL but there are three that report the highest number of cases: hydralazine, procainamide, and isoniazid. While the criteria for diagnosing DIL has not been thoroughly established, symptoms of DIL typically present as muscle pain and joint pain. Generally, the symptoms recede after discontinuing use of the drugs.

Undifferentiated connective tissue disease (UCTD) is a disease in which the body mistakenly attacks its own tissues. It is diagnosed when there is evidence of an existing autoimmune condition which does not meet the criteria for any specific autoimmune disease, such as systemic lupus erythematosus or scleroderma. Latent lupus and incomplete lupus are alternative terms that have been used to describe this condition.

The term is sometimes used interchangeably with mixed connective tissue disease, an overlap syndrome. However, MCTD is thought by some researchers to be a clinically distinct entity and is strongly associated with the presence of high titers of ribonucleoprotein (RNP) antibodies.

It is estimated that up to 25 percent of people with systemic autoimmune disease could be considered to have UCTD.

An overlap syndrome is an autoimmune disease of connective tissue in which a person presents with symptoms of two or more diseases.

Examples of overlap syndromes include mixed connective tissue disease and scleromyositis. Diagnosis depends on which diseases the patient shows symptoms and has positive antibodies for in their lab serology.

In overlap syndrome, features of the following diseases are found (most common listed):

- Systemic lupus erythematosus (SLE),

- Systemic sclerosis,

- Polymyositis,

- Dermatomyositis,

- Rheumatoid arthritis (RA)

- Sjögren's syndrome

- Eosinophilic granulomatosis with polyangiitis (EGPA)

- Autoimmune thyroiditis

- Antiphospholipid antibody syndrome

The treatment of overlap syndrome is mainly based on the use of corticosteroids and immunosuppressants. Biologic drugs, i.e. anti-TNFα or anti-CD20 monoclonal antibodies, have been recently introduced as alternative treatments in refractory cases. There are some concerns with the use of anti-TNF agents in patients with systemic autoimmune diseases due to the risk of triggering disease exacerbations.

The prognosis of mixed connective tissue disease is in one third of cases worse than that of systemic lupus erythematosus (SLE). In spite of prednisone treatment, this disease is progressive and may in many cases evolve into a progressive systemic sclerosis (PSS), also referred to as diffuse cutaneous systemic scleroderma (dcSSc) which has a poor outcome. In some cases though the disease is mild and may only need aspirin as a treatment and may go into remission where no Anti-U1-RNP antibodies are detected, but that is rare or within 30% of cases. Most deaths from MCTD are due to heart failure caused by pulmonary arterial hypertension (PAH).

MCTD combines features of scleroderma, myositis, systemic lupus erythematosus, and rheumatoid arthritis (with some sources adding polymyositis, dermatomyositis, and inclusion body myositis) and is thus considered an overlap syndrome.

MCTD commonly causes:

- joint pain/swelling,

- malaise,

- Raynaud phenomenon,

- muscle inflammation, and

- sclerodactyly (thickening of the skin of the pads of the fingers)

These are also referred to as systemic autoimmune diseases. The autoimmune CTDs may have both genetic and environmental causes. Genetic factors may create a predisposition towards developing these autoimmune diseases. They are characterized as a group by the presence of spontaneous overactivity of the immune system that results in the production of extra antibodies into the circulation. The classic collagen vascular diseases have a "classic" presentation with typical findings that doctors can recognize during an examination. Each also has "classic" blood test abnormalities and abnormal antibody patterns. However, each of these diseases can evolve slowly or rapidly from very subtle abnormalities before demonstrating the classic features that help in the diagnosis. The classic collagen vascular diseases include:

- Systemic lupus erythematosus (SLE) – An inflammation of the connective tissues, SLE can afflict every organ system. It is up to nine times more common in women than men and strikes black women three times as often as white women. The condition is aggravated by sunlight.

- Rheumatoid arthritis – Rheumatoid arthritis is a systemic disorder in which immune cells attack and inflame the membrane around joints. It also can affect the heart, lungs, and eyes. Of the estimated 2.1 million Americans with rheumatoid arthritis, approximately 1.5 million (71 percent) are women.

- Scleroderma – an activation of immune cells that produces scar tissue in the skin, internal organs, and small blood vessels. It affects women three times more often than men overall, but increases to a rate 15 times greater for women during childbearing years, and appears to be more common among black women.

- Sjögren's syndrome – also called Sjögren's disease, is a chronic, slowly progressing inability to secrete saliva and tears. It can occur alone or with rheumatoid arthritis, scleroderma, or systemic lupus erythematosus. Nine out of 10 cases occur in women, most often at or around mid-life.

- Mixed connective tissue disease – Mixed connective-tissue disease (MCTD) is a disorder in which features of various connective-tissue diseases (CTDs) such as systemic lupus erythematosus (SLE); systemic sclerosis (SSc); dermatomyositis (DM); polymyositis (PM); anti-synthetase syndrome; and, occasionally, Sjögren syndrome can coexist and overlap. The course of the disease is chronic and usually milder than other CTDs. In most cases, MCTD is considered an intermediate stage of a disease that eventually becomes either SLE or Scleroderma.

- Undifferentiated connective tissue disease (UCTD) is a disease in which the body mistakenly attacks its own tissues. It is diagnosed when there is evidence of an existing autoimmune condition which does not meet the criteria for any specific autoimmune disease, such as systemic lupus erythematosus or scleroderma. Latent lupus and incomplete lupus are alternative terms that have been used to describe this condition.

- Psoriatic arthritis is also a collagen vascular disease.

A connective tissue disease is any disease that has the connective tissues of the body as a target of pathology. Connective tissue is any type of biological tissue with an extensive extracellular matrix that supports, binds together, and protects organs. These tissues form a framework, or matrix, for the body, and are composed of two major structural protein molecules: collagen and elastin. There are many different types of collagen protein in each of the body's tissues. Elastin has the capability of stretching and returning to its original length—like a spring or rubber band. Elastin is the major component of ligaments (tissues that attach bone to bone) and skin. In patients with connective tissue disease, it is common for collagen and elastin to become injured by inflammation (ICT). Many connective tissue diseases feature abnormal immune system activity with inflammation in tissues as a result of an immune system that is directed against one's own body tissues (autoimmunity).

Diseases in which inflammation or weakness of collagen tends to occur are also referred to as collagen diseases. Collagen vascular diseases can be (but are not necessarily) associated with collagen and blood vessel abnormalities and that are autoimmune in nature. See also vasculitis.

Connective tissue diseases can have strong or weak inheritance risks, and can also be caused by environmental factors.

Chilblain lupus erythematosus (also known as "chilblain lupus erythematosus of Hutchinson") is a chronic, unremitting form of lupus erythematosus with the fingertips, rims of ears, calves, and heels affected, especially in women.

Neonatal lupus erythematosus is the occurrence of systemic lupus erythematosus (SLE) symptoms in an infant born from a mother with SLE, most commonly presenting with a rash resembling discoid lupus erythematosus, and sometimes with systemic abnormalities such as complete heart block or hepatosplenomegaly.

The infants have no skin lesions at birth, but develop them during the first weeks of life. Neonatal lupus is usually benign and self-limited.

It is associated with mothers who carry the Ro/SSA antibodies.

Neuropsychiatric systemic lupus erythematosus or NPSLE refers to the neurological and psychiatric manifestations of systemic lupus erythematosus. SLE is a disease in which the immune system attacks the body's own cells and tissues. It can affect various organs or systems of the body. It is estimated that over half of people with SLE have neuropsychiatric involvement.

Lupus nephritis (also known as SLE nephritis) is an inflammation of the kidneys caused by systemic lupus erythematosus (SLE), an autoimmune disease. It is a type of glomerulonephritis in which the glomeruli become inflamed. As the result of SLE, the cause of glomerulonephritis is said to be "secondary" and has a different pattern and outcome from conditions with a "primary" cause originating in the kidney.

Collagen disease is a term previously used to describe systemic autoimmune diseases (e.g., rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis), but now is thought to be more appropriate for diseases associated with defects in collagen, which is a component of the connective tissue.

The term "collagen disease" was coined by Dr. Alvin F. Coburn in 1932, on his quest to discover streptococcal infection as the cause for rheumatic fever.

Aggravation (or exacerbation) of SLE has been estimated to occur in about 20-30% pregnancies where the mother has SLE. Increased disease activity of SLE is expected during pregnancy because of increased levels of estrogen, prolactin, and certain cytokines. However, a long time of remission before pregnancy decreases the risk of aggravation, with an incidence of 7-33% in women who have been in remission for at least 6 months, and an incidence of 61-67% in women who have active SLE at the time of conception.

Renal disease flare-up is the most common presentation of SLE aggravation in pregnancy, and is seen equally in United States and European populations. Serositis with pleural and pericardial effusions are seen in up to 10% of these patients.

On the other hand, flares of SLE are uncommon during pregnancy and are often easily treated. The most common symptoms of these flares include arthritis, rashes, and fatigue.

Also, in the postpartum period, there may be exacerbations of SLE due to decreased levels of anti-inflammatory steroids, elevated levels of prolactin and estrogen and progesterone changes.

In diagnosing an aggravation of SLE in pregnancy, there need to be a differential diagnosis from SLE-unrelated complications of pregnancy that may appear in a similar fashion. For example, chloasma may appear like the malar rash of SLE, proteinuria from preeclampsia may appear like that of lupus nephritis, thrombocytopenia of the HELLP syndrome may appear like that of SLE, and pregnancy-related edema of joints can appear like arthritis of SLE.

Treatments for inflammatory arthritis vary by subtype, though they may include drugs like DMARDs (disease-modifying anti-rheumatic drugs) and tumor necrosis factor inhibitors.

Class I disease (minimal mesangial glomerulonephritis) in its histology has a normal appearance under a light microscope, but mesangial deposits are visible under an electron microscope. At this stage urinalysis is normal.

Class II disease (mesangial proliferative glomerulonephritis) is noted by mesangial hypercellularity and matrix expansion. Microscopic haematuria with or without proteinuria may be seen. Hypertension, nephrotic syndrome, and acute kidney insufficiency are very rare at this stage.

Class III disease (focal glomerulonephritis) is indicated by sclerotic lesions involving less than 50% of the glomeruli, which can be segmental or global, and active or chronic, with endocapillary or extracapillary proliferative lesions. Under the electron microscopy, subendothelial deposits are noted, and some mesangial changes may be present. Immunofluorescence reveals positively for IgG, IgA, IgM, C3, and C1q. Clinically, haematuria and proteinuria are present, with or without nephrotic syndrome, hypertension, and elevated serum creatinine.

Class IV disease (diffuse proliferative nephritis) is both the most severe, and the most common subtype. More than 50% of glomeruli are involved. Lesions can be segmental or global, and active or chronic, with endocapillary or extracapillary proliferative lesions. Under electron microscopy, subendothelial deposits are noted, and some mesangial changes may be present. Clinically, haematuria and proteinuria are present, frequently with nephrotic syndrome, hypertension, hypocomplementemia, elevated anti-dsDNA titres and elevated serum creatinine.

Class V disease (membranous glomerulonephritis) is characterized by diffuse thickening of the glomerular capillary wall (segmentally or globally), with diffuse membrane thickening, and subepithelial deposits seen under the electron microscope. Clinically, stage V presents with signs of nephrotic syndrome. Microscopic haematuria and hypertension may also been seen. Stage V also can also lead to thrombotic complications such as renal vein thromboses or pulmonary emboli.

A final Class is included by most practitioners, Class VI, or advanced sclerosing lupus nephritis. It is represented by global sclerosis involving more than 90% of glomeruli, and represents healing of prior inflammatory injury. Active glomerulonephritis is not usually present. This stage is characterised by slowly progressive kidney dysfunction, with relatively bland urine sediment. Response to immunotherapy is usually poor. A tubuloreticular inclusion within capillary endothelial cells is also characteristic of lupus nephritis, and can be seen under an electron microscope in all stages. It is not diagnostic however, as it exists in other conditions such as HIV infection. It is thought to be due to the chronic interferon exposure.

Symptoms of inflammatory arthritis include stiffness, pain, and swelling of the joints, restricted motions, and reduced physical strength. Other symptoms may include systemic complaints including fatigue.

For women with systemic lupus erythematosus (SLE), pregnancy can present some particular challenges for both mother and child.

While most infants born to mothers who have SLE are healthy, mothers with SLE as an intercurrent disease in pregnancy should remain under medical care until delivery. In general, women with SLE and, in addition, hypertension, proteinuria, and azotemia have an extra increased risk for pregnancy complications. Pregnancy outcomes in women with SLE who receive renal transplants are similar to those of transplant recipients without SLE.

Women pregnant and known to have anti-Ro (SSA) or anti-La antibodies (SSB) often have echocardiograms during the 16th and 30th weeks of pregnancy to monitor the health of the heart and surrounding vasculature.

Contraception and other reliable forms of pregnancy prevention is routinely advised for women with SLE, since getting pregnant during active disease was found to be harmful. Lupus nephritis was the most common manifestation.

Of live births, approximately one third are delivered prematurely.

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.

The American College of Rheumatology has outlined 19 syndromes that are seen in NPSLE. These syndromes encompass disorders of the central and peripheral nervous systems:

- Aseptic meningitis

- Cerebrovascular disease

- Demyelinating syndrome

- Headache

- Movement disorder

- Myelopathy

- Seizure disorders

- Acute confusional state

- Anxiety disorder

- Cognitive dysfunction

- Mood disorder

- Psychosis

- Acute inflammatory demyelinating polyradiculoneuropathy

- Autonomic disorder

- Mononeuropathy (single/multiplex)

- Myasthenia gravis

- Cranial neuropathy

- Plexopathy

- Polyneuropathy

Each of the 19 syndromes are also stand-alone diagnoses, which can occur with or without lupus.

The majority of cases involve the central nervous system (CNS), which consists of the brain and spinal cord. The CNS syndromes can be subcategorized as either focal or diffuse. The focal syndromes are neurological, while the diffuse syndromes are psychiatric in nature. The most common CNS syndromes are headache and mood disorder.

Though neuropsychiatric lupus is sometimes referred to as "CNS lupus", it can also affect the peripheral nervous system (PNS). Between 10-15% of people with NPSLE have PNS involvement. Mononeuropathy and polyneuropathy are the most common PNS syndromes.