Panniculitis is defined as an inflammation of the subcutaneous tissue of varying aetiology. It may appear in many systemic diseases, and often occurs in patients suffering from systemic inflammatory connective tissue diseases. It is observed mainly in the course of lupus erythematosus discoides (2–3% of patients), but it may be an early symptom of developing the systemic form of lupus erythematosus. In this paper we present a case of a patient with a severe course of panniculitis manifested as a painful, tough and warm skin lesion on the side of the thigh. It was accompanied by systemic symptoms, such as hectic fever, splenomegaly, and lymphadenopathy. In addition, tuberculosis, Lyme disease, salmonellosis and cat scratch disease antibodies were found positive. Despite aggressive antibiotic and anti-inflammatory therapy, there were no satisfactory results. Steroid therapy was attempted (pulses, followed by oral doses of methylprednisolone), which resulted in an effective clinical outcome.