Due to the variety of symptoms and organ system involvement with SLE, its severity in an individual must be assessed in order to successfully treat SLE. Mild or remittent disease may, sometimes, be safely left untreated. If required, nonsteroidal anti-inflammatory drugs and antimalarials may be used. Medications such as prednisone, mycophenolic acid and tacrolimus have been used in the past.

Disease-modifying antirheumatic drugs (DMARDs) are used preventively to reduce the incidence of flares, the progress of the disease, and the need for steroid use; when flares occur, they are treated with corticosteroids. DMARDs commonly in use are antimalarials such as hydroxychloroquine and immunosuppressants (e.g. methotrexate and azathioprine). Hydroxychloroquine is an FDA-approved antimalarial used for constitutional, cutaneous, and articular manifestations. Hydroxychloroquine has relatively few side effects, and there is evidence that it improves survival among people who have SLE.

Cyclophosphamide is used for severe glomerulonephritis or other organ-damaging complications. Mycophenolic acid is also used for treatment of lupus nephritis, but it is not FDA-approved for this indication, and FDA is investigating reports that it may be associated with birth defects when used by pregnant women.

A dermatologist or general physician usually administers combination therapy of drugs used for tuberculosis, such as Rifampicin, Isoniazid and Pyrazinamide (possibly with either streptomycin or ethambutol).

Treatment consists primarily of immunosuppressive drugs (e.g., hydroxychloroquine and corticosteroids). An interesting second line drug is methotrexate in its low-dose schedule. In 2011, the U.S. Food and Drug Administration (FDA) approved the first new drug for lupus in more than 50 years to be used in the US, belimumab. In addition to medicative therapy, due to the psychological and social impacts that Lupus may have on an individual, Cognitive Behavioural Therapy (CBT) has also been demonstrated to be effective in reducing stress, anxiety, and depression in lupus sufferers.

Therapy for cutaneous tuberculosis is the same as for systemic tuberculosis, and usually consists of a 4-drug regimen, i.e., isoniazid, rifampin, pyrazinamide, and ethambutol or streptomycin.

Treatment largely depends upon individual disease progression and the nature of presenting symptoms. Antimalarials, corticosteroids, and other drugs may be prescribed, if deemed appropriate by the treating physician.

Subacute cutaneous lupus erythematosus (SCLE) is a clinically distinct subset of cases of lupus erythematosus that is most often present in white women aged 15 to 40, consisting of skin lesions that are scaly and evolve as polycyclic annular lesions or plaques similar to those of plaque psoriasis.

Characteristically the lesions appear in sun-exposed areas such as the vee of the neckline or the forearms, but not the face. It may be brought on by sun-sensitizing medications, but is usually associated with autoimmune disorders such as rheumatoid arthritis and Sjögren's syndrome.

Treatment generally involves sun avoidance and protection and topical corticosteroids. Sometimes systemic drug treatment is necessary. Besides corticosteroids other immunosuppressants such as methotrexate are also used.

Lesions of SCLE may have an annular configuration, with raised red borders and central clearing.

It is important to recognize early that these drugs are causing DIL like symptoms and discontinue use of the drug. Symptoms of drug-induced lupus erythematosus generally disappear days to weeks after medication use is discontinued. Non-steroidal anti-inflammatory drugs (NSAIDs) will quicken the healing process. Corticosteroids may be used if more severe symptoms of DIL are present.

In longstanding scarred lesions, squamous cell carcinoma can develop.

Drug regimens prescribed for lupus nephritis include mycophenolate mofetil (MMF), intravenous cyclophosphamide with corticosteroids, and the immune suppressant azathioprine with corticosteroids. MMF and cyclophosphamide with corticosteroids are equally effective in achieving remission of the disease. MMF is safer than cyclophosphamide with corticosteroids, with less chance of causing ovarian failure, immune problems or hair loss. It also works better than azathioprine with corticosteroids for maintenance therapy. Individuals with lupus nephritis have a high risk for B-cell lymphoma (which begins in the immune system cells).

No specific cure is known. Treatment is largely supportive. Nonsteroidal anti-inflammatory drugs (NSAIDs) are indicated for tender lymph nodes and fever, and corticosteroids are useful in severe extranodal or generalized disease.

Symptomatic measures aimed at relieving the distressing local and systemic complaints have been described as the main line of management of KFD. Analgesics, antipyretics, NSAIDs, and corticosteroids have been used. If the clinical course is more severe, with multiple flares of bulky enlarged cervical lymph nodes and fever, then a low-dose corticosteroid treatment has been suggested.

Continuing glucocorticoids at the lowest effective dose and/or cautious use of azathioprine may be preferred in some patients, but needs to be weighed against potential adverse effects of such medications.

NSAIDs (non steroid anti-inflammatory drug) are the usual recommended treatment for Löfgren syndrome.

Most patients will maintain a diagnosis of undifferentiated connective tissue disease. However, about one third of UCTD patients will differentiate to a specific autoimmune disease, like rheumatoid arthritis or systemic sclerosis. About 12 percent of patients will go into remission.

Severe vitamin D deficiency has been associated with the progression of UCTD into defined connective tissue diseases. The presence of the autoantibodies anti-dsDNA, anti-Sm, and anti-cardiolipin has been shown to correlate with the development of systemic lupus erythematosus, specifically.

Tumid lupus erythematosus (also known as "lupus erythematosus tumidus") is a rare, but distinctive entity in which patients present with edematous erythematous plaques, usually on the trunk.

Lupus erythematosus tumidus (LET) was reported by Henri Gougerot and Burnier R. in 1930. It is a photosensitive skin disorder, a different subtype of cutaneous lupus erythematosus (CLE) from discoid lupus erythematosus (DLE) or subacute CLE (SCLE). LET is usually found on sun-exposed areas of the body. Skin lesions are edematous, urticarialike annular papules and plaques. Topical corticosteroids are not effective as treatment for LET, but many will respond to chloroquine. LET resolves with normal skin, no residual scarring, no hyperpigmentation or hypopigmentation. Cigarette smokers who have LET may not respond very well to chloroquine.

It has been suggested that it is equivalent to Jessner lymphocytic infiltrate of the skin.

Antinuclear antibodies are usually positive in drug induced Lupus. Anti-Neutrophil Cytoplasmic antibodies (ANCA) can also be positive in association with certain drugs. Furthermore, Anti-Histone antibodies can also be positive in drug induced lupus.

Anti-Histone antibodies are positive in up to 95% of patients with drug induced lupus. DIThe most common medications associated with drug induced lupus are hydralazine, procainamide, isoniazid, methyldopa, chlorpromazine, quinidine, and minocycline.

Verrucous lupus erythematosus (also known as "Hypertrophic lupus erythematosus") presents with non-pruritic papulonodular lesions on the arms and hands, resembling keratoacanthoma or hypertropic lichen planus.

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.

Discoid lupus erythematosus (DLE) is a chronic skin condition of sores with inflammation and scarring favouring the face, ears, and scalp and at times on other body areas. These lesions develop as a red, inflamed patch with a scaling and crusty appearance. The centre areas may appear lighter in colour with a rim darker than the normal skin.

Discoid lupus erythematosus can be divided into localised, generalised, and childhood discoid lupus erythematosus.

Management of neuropsychiatric lupus is similar to the management of neuropsychiatric disease in patients without lupus. Treatment depends on the underlying causes of a patient’s disease, and may include immunosuppressants, anticoagulants, and symptomatic therapy.

Acute cutaneous lupus erythematosus is a cutaneous condition characterized by a bilateral malar rash (also known as a "butterfly rash") and lesions that tend to be transient, and that follow sun exposure.

Lupus erythematosus panniculitis (also known as "Lupus erythematosus profundus", "Lupus panniculitis", "Lupus profundus", and "Subcutaneous lupus erythematosus") presents with subcutaneous nodules that are commonly firm, sharply defined and nontender.

Tufted folliculitis presents with doll's hair-like bundling of follicular units, and is seen in a wide range of scarring conditions including chronic staphylococcal infection, chronic lupus erythematosus, lichen planopilaris, Graham-Little syndrome, folliculitis decalvans, acne keloidalis nuchae, immunobullous disorders, and dissecting cellulitis.

Pemphigus erythematosus (also known as "Senear–Usher syndrome") is simply a localized form of pemphigus foliaceus with features of lupus erythematosus.

Alpha-1 antitrypsin deficiency panniculitis is a panniculitis associated with a deficiency of the α-antitrypsin enzyme.