Lupus usually begins with a series of signs that gradually emerge, in a few days or weeks: fatigue, sometimes fever, joint pain, skin signs, chest pain, shortness of breath...

In other cases, the initial presentation is called monosymptomatic, that is, one clinical sign predominates.

The disease often begins with skin damage, which affects 50 to 75% of patients during the course of the disease.

These skin lesions are stimulated by exposure to the sun, or sometimes simply to ultraviolet light.

This may include:

- An excessive reaction of the skin, with redness such as a "sunburn", after moderate exposure to the sun: this is called photosensitivity.

- Redness in "butterfly wings" on the face (or erythema in "vespertilio", that is to say in bat wing). This rash is located symmetrically on the cheekbones, wings of the nose and sometimes on the forehead. This redness can spread to the neckline and affect the back of the hands and forearms.

- A "discoid" lupus, that is  one which provokes chronic rounded redness, of the same topography, accompanied by scales (crusts), which will unfortunately leave scars.

- In other cases, joint pain or "arthralgia" are present at the beginning of the disease. These are inflammatory joint pains, which interfere with sleep and are characterised by painful stiffening, especially, when the joints are first being used in the morning. Even though we can talk about polyarthritis (or inflammatory rheumatism), joint swelling is rarer than during rheumatoid arthritis. Joint involvement primarily concerns the hands and wrists. Unlike rheumatoid arthritis, this arthritis is not accompanied by destruction of the joints. The joints become painless again with the lull of the disease (that is, with remission) which is favoured by the treatments.

- Sometimes the disease can be revealed by inflammation that affects the membranes that surround the lung (pleurisy) or the heart (pericarditis).

- In other cases, the disease may begin with kidney damage expressed by the presence of proteins (proteinuria) or red blood cells (hematuria) in the urine. This kidney damage is often present as soon as lupus is diagnosed in children.

- Other signs of onset are possible, but are rarer: neurological, psychic, digestive (pancreatitis, hepatitis...), cardiovascular (damage to the valves of the heart, inflammation of the heart muscle, also called myocarditis, arterial or venous thrombosis, also called phlebitis).

Faced with these first clinical signs, it is usually the blood sample that will point towards systemic lupus. Virtually all patients at this stage have autoantibodies, called antinuclear antibodies, in high concentrations. More specific than antinuclear antibodies, anti- native DNA antibodies contribute a lot to the diagnosis.