OVERVIEW
It is a non-suppurative inflammatory disease originating in the adipose lobules with recurrent subcutaneous nodules all over the body as the main symptom, which can involve multiple systems. The etiology is still unclear, and may be related to infection, autoimmune response, and pharmacological factors, etc. The main treatment is mainly pharmacological, and symptomatic treatment is provided in the event of visceral involvement.
Definition
Nodular lipomatitis is a non-suppurative inflammatory disease originating in the adipose lobules [1].
Clinical manifestations are varied and lack specificity, mainly manifesting as subcutaneous nodules, fever and visceral damage, often accompanied by chills, shivering, arthralgia, skin breakdown, malaise, cough, chest tightness and breathlessness, muscle aches and pain, abdominal pain and other non-specific symptoms [2].
Typing
According to whether the lesion involves internal organs or not, it is divided into 2 types
Cutaneous type nodular lipomatitis
The lesions only invade the subcutaneous adipose tissue and do not involve internal organs.
Systemic type nodular lipomatitis
In addition to the cutaneous form, there is also involvement of internal organs.
Morbidity
This is a rare disease, and there is no exact incidence of lipomatosis nodularis at home or abroad.
Lipomatous nodular meningitis occurs in about 75% of women and can occur at any age, but is most common in the 30s and 50s. There is no racial difference in incidence [1].
Causes
Causes
The etiology of nodular lipomatosis is unknown. However, it is thought that it may be related to disorders of fat metabolism or abnormalities of enzymes affecting fat metabolism, allergic reactions caused by infections, autoimmune reactions, and drug factors.
In recent years, research findings have shown that this disease may not be a single disease, but rather a focal lipofollicular lipomatitis caused by autoimmunity, tumors, infections, drugs, and some other unknown etiologies [3].
Risk factors
People with any one or more of the following risk factors are more likely to develop the disease.
Chemical factors
Such as prolonged exposure to halogenated compounds such as iodine and bromine, and use of drugs such as quinine, sulfa, and antimony.
Food Factors
e.g. long-term consumption of synthetic low-calorie sweeteners, excessive alcohol consumption, etc.
Symptoms
Main Symptoms
Clinical manifestations are varied and lack specificity, and are mainly characterized by subcutaneous nodules, fever and internal organ damage. According to whether there is obvious internal organ involvement, it can be divided into two subtypes: cutaneous type and systemic type.
Cutaneous type
Skin lesions are common on the trunk and proximal limbs, mainly on the thighs, buttocks and abdomen.
The lesions are firm subcutaneous nodules or plaques, medium or firm in texture, varying in size from mung bean to palm size, with clear borders. Usually 3 to 4, can be as many as dozens.
The surface of the lesions has normal skin color or is adherent to the skin and is pale red, dark red or purple-brown. Most of the damages have mild pressure pain; a few nodules may be necrotic and ruptured, exuding a lipid-like substance, but non-suppurative. After a few days or weeks, the nodules gradually subside and disappear without leaving marks or pigmentation, some of which are slightly depressed in the center.
About 20% of patients may have fever when the lesions flare up, and a few have joint pain and enlarged lymph nodes.
Systemic type
Fever
Almost all patients with the systemic form have peripheral symptoms such as fever, malaise, malaise, etc. Fever can be as high as 40°C or above.
Joint pain
About 20% of patients are accompanied by joint pain, which is most common in both knees, followed by wrists and ankles, occasionally in a wandering pattern.
Muscle pain
About 10% of patients with muscle pain, mostly located in the proximal extremities, such as the upper arms and thighs.
Superficial lymph node enlargement
About 15% of patients have superficial lymph node enlargement, mostly in the axilla, followed by the groin. They are usually the size of a broad bean to an apricot kernel, ranging from one to many.
Digestive symptoms
Digestive symptoms are most common, including anorexia, nausea, abdominal pain, jaundice and even blood in stool. About half of the cases have liver and spleen enlargement. In addition, mesenteric or ileocecal involvement is also more common, and a mass can be detected in the abdomen with localized pressure pain.
Respiratory symptoms
Some patients may have chest pain, dyspnea and other respiratory symptoms.
Urinary system symptoms
Transient renal insufficiency may occur when the kidneys are involved, which may cause focal segmental glomerulosclerosis, and renal puncture may show changes in the renal parenchyma.
Other symptoms
Other manifestations of systemic lipofuscinosis, such as retroocular involvement, causing retinal vasculitis, ocular depression; the tongue may appear ulcers; or myocarditis, pericarditis.
In severe cases, mental abnormality, spasm, limb paralysis, lethargy and so on.
Disseminated intravascular coagulation leading to extensive hemorrhage may occur in the later stages of severe cases.
Medical Treatment
Department of Medicine
Department of Rheumatology and Immunology
If symptoms such as recurrent general discomfort, joint pain, muscle pain, subcutaneous nodules on the trunk and limbs occur, it is recommended to consult the Department of Rheumatology and Immunology of a regular hospital.
Dermatology
If you have recurrent erythema and subcutaneous nodules (hard, round or oval painless nodules under the skin), we recommend that you consult a dermatologist promptly.
Emergency Department
In the event of an emergency such as severe respiratory distress or profuse blood in the stool, it is recommended that you consult the Emergency Department immediately.
Preparation
Preparation for medical consultation: registration, preparation of documents, frequently asked questions
Tips for seeking medical treatment
If you have facial lesions, avoid using cosmetics before the visit to avoid masking the condition.
Keep an accurate and complete record of the development and characteristics of your condition so that you can give your doctor more references.
Preparation List
Symptom list
Especially focus on the time of onset of symptoms, special manifestations, etc.
Are there nodules under the skin? In what part of the body?
Is there any pain or tenderness in the nodule?
Has the subcutaneous nodule ever broken? Is there any oily fluid coming out of the ulcerated nodule?
Is there any fever? What is the highest degree?
Are there any symptoms of general malaise, arthralgia, etc.?
Are there any symptoms such as nausea, vomiting, abdominal pain, jaundice, etc.?
Are there any gastrointestinal symptoms such as abdominal masses, blackened stools, etc.?
Are there any symptoms such as dyspnea, chest pain, etc.?
Are there any symptoms such as eye discomfort, limb paralysis, spasms, etc.?
Is there any abnormal expression of mental status?
List of medical history
Any history of autoimmune diseases such as rheumatic fever, scleroderma, dry syndrome, myositis and vasculitis?
Is there chronic exposure to halogenated compounds such as iodine and bromine, or chronic use of medications such as quinine, sulfonamide, and antimony?
Checklist
Test results of the last six months, which can be brought to the doctor’s office
Laboratory tests: routine blood test, urine test, routine stool test, blood biochemistry (including liver and kidney function, blood sedimentation, C-reactive protein, etc.), immunology test (including serum immunoglobulin, complement, etc.), blood amylase, urine amylase, etc.
Imaging examination: chest X-ray, MRI of internal organs.
Pathologic examination: histologic examination.
Medication list
Medication used in the last three months, if available, bring the box or package to the doctor’s appointment
Non-steroidal anti-inflammatory drugs: aspirin, indomethacin, etc.
Glucocorticoids: prednisone, dexamethasone, etc.
Immunosuppressants: azathioprine, hydroxychloroquine, thalidomide, cyclophosphamide, cyclosporine, merti-macrolide, etc.
Other drugs: tetracycline, etc.
Diagnosis
Diagnosis is based on
Medical history
Medical history is not necessary for the diagnosis of the disease, but the presence of the following medical history may provide some reference for the diagnosis of the disease.
History of autoimmune diseases such as rheumatic fever, scleroderma, dry syndrome, myositis and vasculitis.
Prolonged exposure to halogenated compounds such as iodine and bromine, or prolonged use of drugs such as quinine, sulfonamide, and antimony.
Clinical manifestations
Symptoms
Prevalent in young adult females.
It is characterized by recurrent and batch appearance of subcutaneous nodules, which have pain and significant tenderness, and after fading, the local skin appears to have varying degrees of depression and hyperpigmentation.
It is often accompanied by systemic symptoms such as fever, arthralgia and myalgia.
When the lesion invades the visceral adipose tissue, different symptoms may appear depending on the site of involvement. If the internal organs are extensively involved, multiple organ failure, hemorrhage or infections may occur.
Physical signs
The affected skin surface is light red, dark red, purple-brown or normal skin color, and the subcutaneous nodules are slightly higher than the skin surface, with firm texture and may be painful to touch.
When the nodule is located in the deeper part of the skin, it can move mildly, and when the location is shallow, it is adherent to the skin and has little mobility.
Laboratory Tests
Blood tests
Routine blood tests can be performed to determine whether the patient is anemic and whether there is a decrease in white blood cells and platelets to determine whether there is bone marrow involvement.
A mild increase in the total number of white blood cells may be seen in the early stages of lipoid nodular membranitis; bone marrow suppression, which may be characterized by a decrease in white blood cells and platelets and a decrease in hemoglobin, is usually indicative of advanced disease.
Urinalysis
Routine urine tests may reveal the presence of hematuria and proteinuria to determine whether the kidneys are involved.
If the test result shows the presence of red blood cells and protein in the urine, it suggests that there may be kidney damage.
Stool routine
The presence of gastrointestinal bleeding can be clarified by fecal occult blood. A positive fecal occult blood test is seen when there is >5ml of gastrointestinal bleeding per day.
A positive fecal occult blood test can be seen after nodular lipomatosis involving the digestive system.
Blood biochemistry
Mainly includes liver and kidney function, blood sedimentation, C-reactive protein and so on.
To find out whether the patient is infected and to assess liver and kidney function, they are used to determine whether there is liver, kidney and other organs involved in nodular lipomatosis and whether lesions have occurred.
Liver function helps to determine the presence of liver disease, such as alanine aminotransferase, aspartate aminotransferase elevation, suggesting that there may be liver damage; renal function helps to determine the presence of kidney damage, such as blood creatinine elevation, suggesting that there may be kidney disease.
Blood sedimentation and C-reactive protein help to determine the presence of infection. If there are elevated blood sedimentation and C-reactive protein, it can suggest that the body may be infected, which can be important to the diagnosis of the disease.
Immunologic tests
These include immunoglobulins and complement. Immunologic tests assist in the diagnosis.
Blood and urine amylase
Blood and urine amylase tests are used in the differential diagnosis of pancreatic seborrhea.
If blood and urine amylase are normal, it often suggests nodular lipomatosis; if blood and urine amylase are elevated, pancreatic lipomatosis may be considered.
Imaging
Chest X-ray
It can be used to observe the presence or absence of lung lesions.
If the chest X-ray shows thickening and disorganization of the texture of both lungs and patchy shadow in the lungs, it can suggest lung lesions, which can be used to assist in determining whether nodular lipomatosis involves respiratory system lesions or not.
MRI examination of internal organs
It can be used to clarify whether there is a combination of internal organ damage.
If the examination result suggests that bleeding or obstruction occurs in the organs, it is likely to suggest that nodular lipomatitis is associated with internal organ damage.
Histologic examination
Pathologic histological examination of skin nodules is mainly used to clarify the nature and staging of nodules, which is the main basis for diagnosis. According to the development of its course, the pathology can be divided into acute inflammatory stage, phagocytic stage, and fibrotic stage [2-3].
If in the lobules adipose tissue is degenerated and necrotic with infiltration of neutrophils, lymphocytes and histiocytes, partly accompanied by vasculitis changes, it suggests acute inflammatory stage.
If there is a large number of macrophages infiltrating in the degenerated and necrotic adipose tissue, phagocytosis of degenerated adipocytes and formation of characteristic foam cells, it can suggest phagocytosis stage.
If a large number of foam cells reduce or disappear, replaced by fibroblasts; the inflammatory response disappears, and fibrotic tissue tissue is formed, which can suggest fibrosis stage.
Differential diagnosis
Erythema nodosum
Similarity: both have the clinical manifestation of subcutaneous nodules.
Differences: the nodules of erythema nodosum are distributed on the extensor side of the calf, do not break down, and the nodules subside after 3-4 weeks. After subsiding, no localized skin depression occurs, and the systemic symptoms are milder.
Polyarteritis nodosa
Similarity: both have the clinical manifestation of subcutaneous nodules.
Differences: Nodular vasculitis mainly invades medium-sized blood vessels. Nodules can also occur in the lower legs, arranged along the blood vessels, most often accompanied by peripheral nerves, kidneys and digestive system. The pathology is a generalized necrotizing vasculitis, which occurs at the bifurcation of the arteries, often in a segmental distribution.
Sclerosing erythema
Similarity: both have the clinical manifestation of subcutaneous nodules.
Differences: the nodules of erythema rigidum are purplish-red in color, located on the flexor side of the calf, and break down to form an excavated ulcer with a slow course. Pathology was tuberculous granuloma-like changes with marked vasculitis changes.
Subcutaneous lipomatosis-like T-cell lymphoma
Similarity: both have the clinical manifestation of subcutaneous nodules.
Differences: Subcutaneous lipomatosis-like T-cell lymphoma is a rare lymphoma, accounting for less than 1% of all cutaneous T-cell lymphomas. It is characterized by hard skin lesions, which are followed by deep, well-defined ulcers with secretions and often accompanied by a foul odor. Systemic symptoms are obvious, manifesting as high fever, hepatosplenomegaly, and pancytopenia, and the disease progresses rapidly [4].
Treatment
Aim of treatment: to relieve skin damage as soon as possible, to reduce internal organ damage and the deterioration of the disease caused by internal organ involvement, and to reduce the death rate.
Principles of treatment: there is no specific treatment at present. It is mainly to remove the suspected causes, control infection, apply glucocorticoids and immunosuppressants when necessary, and timely symptomatic treatment for those with visceral damage.
General treatment
Remove the suspected cause of disease, such as eliminating the infected foci and stopping the use of suspected disease-causing drugs. Appropriate use of antibiotics to control infection.
Avoid traumatization of the skin affected area.
If there is no digestive system involvement, diet list, nutritional balance can be, generally no special dietary contraindications.
Medications
Non-steroidal anti-inflammatory drugs (NSAIDs)
For patients with fever, arthralgia and general malaise, they can control body temperature and reduce joint pain. They have antipyretic, analgesic and anti-inflammatory effects and improve joint and muscle discomfort.
Commonly used drugs include aspirin and indomethacin.
Common adverse reactions are symptoms of gastrointestinal irritation, liver damage and increased risk of bleeding.
Note that it is contraindicated in bleeding disorders and asthma, and used with caution in pregnant women.
Glucocorticoids
For acute exacerbations of the disease, especially in patients with acute exacerbations such as fever. It can make the body temperature drop and the nodules disappear, but the symptoms can recur in some cases after reducing the dosage or stopping the drug.
Commonly used drugs include prednisone and dexamethasone.
Common adverse reactions are centripetal obesity, full moon face, buffalo back, acne, hirsutism, edema, hyperlipidemia, hyperglycemia or aggravation of diabetes mellitus, amenorrhea, muscle wasting, weakness, osteoporosis, necrosis of the femoral head, and inhibition of growth and development in children.
Note that the elderly and menopausal women are prone to osteoporosis after use. Pregnant and lactating women should use with caution.
Immunosuppressant
Applicable to patients with severe diseases. With strong anti-inflammatory effect, can inhibit the release of inflammatory transmitters and inflammatory response.
Commonly used drugs are azathioprine, hydroxychloroquine, thalidomide, cyclophosphamide, cyclosporine, mertiomacrophenol ester and so on.
Common adverse effects of the drug include dizziness, nausea, vomiting, rash, alopecia, diarrhea, bone marrow suppression, leukopenia, and liver damage.
Attention to allergy, pregnant women, lactating women prohibited; the elderly, children should be used with caution.
Tetracycline
It is a broad-spectrum bacteriostatic agent with bactericidal effect at high concentration, and can be used in the treatment of infections because of its possible anti-lipase activity.
Common adverse reactions are nausea, vomiting, epigastric discomfort, bloating, diarrhea, hepatotoxicity, and rash.
Note hypersensitivity, pregnant and lactating women, and children under 8 years of age are contraindicated; use with caution in elderly patients.
Prognosis
Cure
The prognosis of cutaneous type of nodular lipofuscinosis is generally good, only skin damage after active treatment, although there are recurrent episodes and the process of remission, but after a few years can be completely relieved.
Those with significant systemic involvement have a poor prognosis, and death may occasionally occur in severe cases. The main causes of death are sepsis, liver failure, hemorrhage and thrombosis [5].
Prognostic factors
Factors affecting the prognosis of patients include the presence of systemic involvement and the time at which systemic involvement occurs.
Those with significant systemic involvement have a poorer prognosis.
Those with systemic involvement occurring before skin damage have a poorer prognosis.
Hazards
Nodular lipomatosis can be life-threatening due to severe visceral involvement.
Scarring may occur after the nodules have broken down and healed, which can be aesthetically displeasing.
Recurrent skin damage can affect the patient’s quality of life.
Daily
Daily Management
Dietary management
There is no special dietary requirement for nodular lipofuscinosis, but a healthy lifestyle should be followed. The diet should be light, coarse and fine, rich in nutrients, with more fresh vegetables and moderate amount of fruits.
If visceral involvement occurs, pay attention to dietary contraindications according to the organs involved, such as gastrointestinal symptoms should eat easy-to-digest soft food; severe gastrointestinal hemorrhage or intestinal perforation occurs, and should be fasted in the acute stage; when liver and kidney function are abnormal, attention should be paid to low-salt, low-fat and high-quality protein diet.
Stop smoking and drinking.
Exercise management
If there is no visceral involvement, there is no special contraindication to exercise, but care should be taken to avoid injury to the skin lesions.
Patients with severe visceral involvement should pay attention to rest and stay in bed strictly during the acute stage.
If the visceral involvement is not serious, patients should choose the appropriate exercise mode according to their own conditions, and the exercise should not be fatiguing.
Psychological support
Maintain optimism in daily life, face the disease positively and establish confidence in overcoming the disease.
Family members should care more about the patient, sympathize with the patient’s mood, and give encouragement and support.
Skin management
Keep the skin lesions clean and do not scratch or rub them to avoid ulceration and infection.
If the skin lesions are already broken, keep them clean and dry, and if necessary, consult a doctor for sterilization to avoid infection.
Try to use non-irritating cleaning products to clean the lesions, and use cotton hand towels or paper towels to wipe the lesions, and be as gentle as possible.
Disease monitoring
Observe the location and size of the lesions to assess the efficacy of the treatment.
After the lesions disappear, you should also pay attention to observation, timely detection of recurrence of symptoms, timely treatment.
Monitor the body temperature to know whether the fever is relieved and assess the efficacy of treatment.
Systemic involvement should be observed to see if the corresponding symptoms are relieved to assess the efficacy of treatment.
Follow-up
Regular follow-ups will help to understand the recovery of the disease and allow for timely treatment of any abnormalities.
If there is any change in the condition, follow-up should be made promptly. If the condition is stable after discharge, it is recommended to review the relevant indexes every 3 to 6 months.
Blood tests, urine tests, blood sedimentation, C-reactive protein, liver and kidney functions, immunological tests, etc. may be needed.
Prevention
There are no effective preventive measures for lipomatosis nodosa, but changing one’s behavior or lifestyle can help reduce the risk of developing the disease.
Patients with infections and immunologic diseases should be treated aggressively to avoid complications of the disease.
Try to avoid the use of halogenated compounds such as iodine and bromine and drugs such as quinine, sulfonamide and antimony.
Try to avoid long-term consumption of synthetic low-calorie sweeteners and alcohol.