bubble_chart Overview

This disease is also known as idiopathic lobular panniculitis, Weber-Christian syndrome, or relapsing febrile nonsuppurative panniculitis. It was first reported by Pfeifer in 1882, followed by Weber who described its relapsing and nonsuppurative characteristics. In 1928, Christian further emphasized its febrile nature. However, many cases without fever have been reported to date.

bubble_chart Etiology

The cause of the disease remains unclear and may be related to the following factors:

1. Abnormal immune response: Abnormal immune responses can be triggered by stimulation from various antigens, such as bacterial infections, food, and medications. Some cases have been reported with recurrent tonsillitis prior to the onset of the disease. There are also reports of the disease occurring after ileal bypass surgery, where bacterial overgrowth occurs in the blind loop. Additionally, halogen compounds such as iodine and bromine, as well as medications like sulfonamides, quinine, and antimony agents, may induce the disease.

2. Lipid metabolism disorder: Reports indicate that the disease is associated with abnormalities in certain enzymes involved in lipid metabolism. For example, there may be a grade I increase in serum lipase or the presence of active pancreatic and lipase enzymes in skin lesions. Some studies have also found a deficiency of α-1 antitrypsin in this disease. While this antitrypsin deficiency may not directly cause lipomembranous inflammation, it could lead to dysregulation of immunological and inflammatory responses.

bubble_chart Pathological Changes

The pathological changes are characterized by necrosis and degeneration of fat cells, which can be divided into three stages. The initial stage [first stage] is the acute inflammatory phase, which is relatively short and features fat cell degeneration accompanied by infiltration of neutrophils, lymphocytes, and histiocytes. Neutrophils may be abundant but do not form abscesses. The intermediate stage [second stage] is the macrophage phase, where, in addition to a few lymphocytes and plasma cells, many histiocytes engulf dissolved fat droplets, transforming into foam cells and lipophagic giant cells. During this stage, neutrophils decrease and eventually disappear. This phase has diagnostic significance. The late stage [third stage] is the fibrosis phase, where foam cells diminish, and fibroblasts proliferate alongside lymphocytes and some plasma cells, eventually leading to extensive collagen fiber proliferation and fibrosis.

bubble_chart Clinical Manifestations

1. Skin lesions: Subcutaneous nodules are the main characteristic of this disease. Their diameter is usually 1–2 cm, but larger ones can exceed 10 cm. Some nodules initially develop subcutaneously and gradually protrude upward, with the skin surface showing grade I elevation, presenting as erythema and slight swelling; others remain hidden beneath the skin, with the overlying skin appearing normal in color but often adhering to the nodules, resulting in limited mobility. Pain and tenderness are prominent. Nodules often occur in batches, symmetrically distributed, with a predilection for the buttocks and lower limbs, though they may also appear on the forearms, trunk, and face. After several weeks or months, the nodules resolve spontaneously, leaving localized skin depressions and pigmentation. This is due to fat necrosis, atrophy, and fibrosis at the lesion site. Nodules recur every few weeks or months, often accompanied by fever of varying patterns—low-grade, irregular, or high fever, which can reach 40°C, presenting as a remittent fever lasting 1–2 weeks before gradually subsiding. Besides fever, symptoms may include lack of strength, loss of appetite, and muscle and joint pain.

Occasionally, a few nodules may involve the overlying skin during fat necrosis, leading to necrosis and ulceration, with discharge of a yellow-brown oily fluid, referred to as "liquefying panniculitis."

2. Visceral involvement: Visceral lesions may appear simultaneously with skin lesions; in some cases, skin lesions precede visceral involvement, while in rare cases, extensive visceral involvement occurs before skin lesions. The clinical symptoms of visceral damage depend on the affected organ, with characteristic signs often becoming apparent only when the lesions are substantial. Liver involvement may manifest as right hypochondriac pain, hepatomegaly, jaundice, and abnormal liver function. Small intestine involvement can lead to steatorrhea and intestinal perforation. Involvement of the mesentery, greater omentum, and retroperitoneal fat tissue may cause upper abdominal pain, abdominal distension and fullness, and palpable masses. Additionally, the bone marrow, lungs, pleura, myocardium, pericardium, spleen, kidneys, and adrenal glands may also be affected. Patients with extensive visceral involvement have a poor prognosis and may die from circulatory failure, hemorrhage, sepsis, or renal failure.

Winkelmann and Bowie reported a variant of nodular panniculitis, termed histiocytic cytophagic panniculitis. This is also a systemic disease characterized by panniculitis. They suggested that this condition is related to nodular panniculitis, with patients ultimately succumbing to hemorrhage. The fatal bleeding is associated with intravascular coagulation and liver failure. The distinction between this disease and nodular vasculitis lies in its abnormal hemorrhagic diathesis and the presence of numerous histiocytes in the bone marrow, lymph nodes, liver, spleen, serous membranes, and subcutaneous fat.

bubble_chart Auxiliary Examination

The erythrocyte sedimentation rate is significantly increased, with grade I leukocyte hyperplasia. If the liver and kidneys are involved, there may be abnormal liver and kidney function, presenting with hematuria and proteinuria. Some cases may exhibit immunological abnormalities such as decreased complement levels, elevated immunoglobulins, and reduced lymphocyte transformation rates. Bone marrow involvement can lead to anemia, leukopenia, and thrombocytopenia.

bubble_chart Diagnosis

The disease is characterized by recurrent subcutaneous nodules in batches. The nodules are painful and markedly tender, often accompanied by fever during most episodes. Diagnosis can be confirmed by combining the intermediate stage [second stage] histopathological findings.

bubble_chart Treatment Measures

There is no specific treatment for this disease. Fibrinolytic drugs, chloroquine, azathioprine, and cyclophosphamide have shown some efficacy. During the acute inflammatory phase or in cases with high fever, glucocorticoids such as prednisone (40–60 mg daily) and nonsteroidal anti-inflammatory drugs (NSAIDs) are significantly effective.

bubble_chart Differentiation

1. Erythema nodosum: More common in spring and autumn. The nodules are mostly limited to the extensor side of the lower legs, symmetrically distributed, without ulceration, and resolve spontaneously within 3–4 weeks, leaving local depressed atrophy at the subsided sites. There is no visceral damage, and systemic symptoms are mild.

2. Erythema induratum: The nodules are dark red, located in the middle and lower parts of the flexor side of the lower legs, and form punched-out ulcers after rupture. Histopathology shows subcutaneous nodular granulomas.

3. Subcutaneous lipogranulomatosis: After the nodules subside, no atrophic depression remains. There are no systemic symptoms, and the condition tends to heal spontaneously.

4. Subcutaneous nodular fat necrosis caused by pancreatitis or pancreatic cancer: The clinical symptoms are similar to those of nodular panniculitis, but histopathological findings show more severe fat cell necrosis, accompanied by thick and indistinct cell walls and anucleate shadow cells.

5. Other diseases: Certain lymphomas, leprosy, and subcutaneous fat necrosis caused by trauma or foreign bodies should be differentiated from nodular panniculitis. {|104|}