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

disease cause 学

The cause of the disease is still unclear, but 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 drugs. Some cases have been reported with recurrent tonsillitis prior to the onset of the disease. There are also reports of this 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 drugs like sulfonamides, quinine, and antimony agents, may induce this disease.

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

Pathological changes

The hallmark of the disease is necrosis and degeneration of fat cells. The pathological changes can be divided into three stages: The initial stage [first stage] is the acute inflammatory phase, which is relatively short and characterized by 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, becoming foam cells and lipophagic giant cells. Neutrophils decrease or disappear during this stage, which has diagnostic significance. The late stage [third stage] is the fibrotic phase, where foam cells decrease, 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 feature of this disease. They are usually 1-2 cm in diameter, but larger ones can exceed 10 cm. Some nodules initially develop under the skin and gradually protrude, causing grade I elevation of the skin surface, presenting as erythema and small swellings; 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. The nodules often occur in batches and are symmetrically distributed, commonly appearing on 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 due to fat necrosis, atrophy, and fibrosis at the lesion sites. The nodules recur every few weeks or months, often accompanied by fever of varying patterns—low-grade, irregular, or high fever (up to 40°C), typically remittent and lasting 1-2 weeks before gradually subsiding. In addition to 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 the discharge of a yellow-brown oily fluid, a condition referred to as "liquefying panniculitis."

2. Visceral involvement: Visceral lesions may appear simultaneously with skin lesions, follow skin lesions, or, in rare cases, precede them. The clinical symptoms of visceral involvement depend on the affected organs, with characteristic signs often becoming apparent only when the lesions are extensive. Liver involvement may manifest as right hypochondriac pain, hepatomegaly, jaundice, and abnormal liver function. Small intestine involvement can lead to steatorrhea and intestinal perforation. Lesions in the mesentery, greater omentum, or retroperitoneal fat tissue may cause epigastric 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. Widespread visceral involvement carries a poor prognosis, with potential fatalities due to 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, like nodular panniculitis, can lead to fatal hemorrhage, which is associated with intravascular coagulation and liver failure. The disease differs from nodular vasculitis in its abnormal hemorrhagic diathesis and the presence of numerous histiocytes in the bone marrow, lymph nodes, liver, spleen, serous membranes, and subcutaneous fat.

[Ancillary tests]

The erythrocyte sedimentation rate is significantly elevated, and leukocyte grade I hyperplasia may occur. If the liver or kidneys are involved, abnormal liver or kidney function may be observed, including 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 batches of subcutaneous nodules. The nodules are painful and markedly tender, with most episodes accompanied by fever. 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 yet. Fibrinolytic drugs, chloroquine, azathioprine, cyclophosphamide, etc., have shown some efficacy. During acute inflammation or in cases with high fever, glucocorticoids such as prednisone (40-60 mg daily) and nonsteroidal anti-inflammatory drugs (NSAIDs) demonstrate significant effectiveness.

bubble_chart Differentiation

1. Erythema nodosum: More common in spring and autumn. The nodules are mostly confined to the extensor side of the lower legs, symmetrically distributed, do not ulcerate, and resolve spontaneously within 3–4 weeks, leaving local depressed atrophy at the subsided sites. No visceral damage occurs, and systemic symptoms are mild.

2. Erythema induratum: The nodules are dark red, located on the middle and lower parts of the flexor side of the lower legs, and form punched-out ulcers after ulceration. Histopathology reveals 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: Its clinical symptoms resemble 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 must be differentiated from nodular panniculitis. {|104|}