| disease | Sarcoidosis |
| alias | Besnier's Lupus Pernio, Boeck's Sarcoid, Sarcoidosis, Schaumann Benign Lymphogranulomatosis, Systemic Fleshy Tumor Disease, Meat-like Tumor Diseases |
Sarcoidosis, also known as sarcoid tumor diseases, Boeck's sarcoid, Schaumann's benign lymphogranulomatosis, and Besnier's chilblain lupus, is a chronic granulomatous disease. In addition to firm, non-ulcerating, and asymptomatic skin lesions, it can also invade mucous membranes, lymph nodes, bones, and internal organs, making it a systemic fleshy tumor disease.
bubble_chart Etiology
The cause of the disease is currently unknown. In the past, it was considered one of the subcutaneous nodule diseases, but the evidence is insufficient. Other atypical mycobacteria have also been proposed as the cause of the disease. Other factors such as viral infections and genetic influences have been suggested, but have not been confirmed.
In recent years, it has been believed that the disease is related to immune responses. Particularly, T-cell-mediated immune responses play an important role. Under the stimulation of certain pathogenic antigens, T cells and macrophages at the lesion site are activated. The activated T cells release a large amount of monocyte chemotactic factors and macrophage migration inhibitory factors, causing the aggregation of monocytes; activated macrophages release interleukin-1, leading to the proliferation of T cells, thus the early lesions are mainly characterized by the infiltration of T cells, monocytes, and macrophages. As the disease progresses, a large number of epithelioid cells are produced, forming typical nodular granulomas. In the late stage [third stage] of the disease, fibroblast proliferation occurs, eventually leading to extensive fibrosis.
bubble_chart Pathological Changes
Nodules generally occur within the dermis or subcutaneous tissue. The primary change is the infiltration of epithelioid cells. These epithelioid cells aggregate into clusters, containing a few giant cells or none at all, surrounded by a small number of lymphocytes, but without caseous necrosis. Occasionally, fibrinoid necrosis occurs at the center of the cell clusters. The connective tissue around the epithelioid cell clusters proliferates, and with silver staining, reticular fibers can be seen surrounding and penetrating the epithelioid cell clusters. Small blood vessels are visible within the cell clusters. Giant cells can be seen in these lesions, and occasionally Schaumann bodies or asteroid bodies are present. Schaumann bodies are oval or round and calcified. Due to the presence of calcium, they stain a deep blue. Asteroid bodies, when stained with phosphotungstic acid Sappan Wood, have a brownish-red center and blue rays. These two bodies can also be seen in other granulomas such as subcutaneous nodes and leprosy, and are not unique to sarcoidosis. When sarcoidosis granulomas regress, the epithelioid cells gradually disappear, leading to the formation of fibrosis.
bubble_chart Clinical ManifestationsSarcoidosis is a systemic granulomatous disease that affects the skin and many internal organs. The involved areas, besides the skin, include the lungs, mediastinum and peripheral lymph nodes, phalanges, myocardium, central nervous system, liver, spleen, kidneys, eyes, and parotid glands. Sarcoidosis can involve only one organ or tissue, or multiple organs or tissues simultaneously. The disease progresses slowly, with alternating periods of remission and relapse. The clinical symptoms of this disease are diverse.
1. Skin manifestations The skin manifestations of sarcoidosis are varied, often presenting as papules, nodules, patches, erythroderma, psoriasis-like lesions, scar sarcoidosis, hypopigmentation, and alopecia. The skin lesions are asymmetrically distributed on the face and limbs. The rashes are firm and elastic to the touch, gradually extending to the subcutaneous layer and involving the entire thickness of the dermis. Epidermal changes are not obvious, with slight thinning, discoloration, telangiectasia, and some scaling. They are often light red to purplish-brown, do not ulcerate, and are asymptomatic.
(1) Papular sarcoidosis The lesions are small nodules the size of a pinhead to a pea, also known as foxtail millet-like sarcoidosis. They are mainly distributed on the face, neck, and shoulders. When pressed with a glass slide, they show small yellowish dots similar to lupus nodules, which disappear without leaving traces, sometimes leaving pigmented spots, atrophy, and scars.
(2) Patch-type sarcoidosis Hutchinson first reported this unique patch-like lesion, which is a large, lobulated, slightly raised, flat-surfaced nodular patch, commonly seen on the cheeks, nose, and arms.
(4) Chilblain-like lupus type Infiltrative bluish-red or purplish-red patches appear symmetrically in areas prone to chilblains, such as the ears, cheeks, nose tip, and fingers/toes.
(5) Subcutaneous sarcoidosis Also known as Darier-Roussy sarcoidosis. Firm subcutaneous nodules the size of beans to foxtail millet, adherent to the skin, with grade I violet-colored epidermis, commonly seen on the trunk, rarely on the face, and asymptomatic.
(6) Scar sarcoidosis Lesions occur at scar sites, such as after burns, folliculitis, or herpes zoster scars. The original scar area expands, and the height increases, resembling keloids.
(7) Erythrodermic sarcoidosis Diffusely distributed infiltrative erythema and scaly patches with unclear boundaries.
(8) Erythema nodosum-type sarcoidosis Some sarcoidosis patients present with multiple arthralgia accompanied by fever, increased erythrocyte sedimentation rate, and hilar lymphadenopathy on X-ray. Painful subcutaneous nodules appear scattered on the face, back, and extensor surfaces of the limbs. The overlying skin is red, most commonly seen in young women.
(9) Mucosal sarcoidosis Pinhead-sized papules on the hard palate, cheeks, uvula, and tonsils, clustering to form flat patches, with small nodules on the conjunctiva and lacrimal glands.
(10) Other skin lesions Sarcoidosis can be associated with subcutaneous calcification, prurigo, erythema multiforme, and folliculitis. Skin atrophy, hyperkeratosis, increased or decreased pigmentation can also be caused by this disease.
2. Other organ involvement Sarcoidosis is a systemic disease, and besides skin lesions, many other organs are involved.
(2) Eye Damage Sarcoidosis affects the eyes in about 25-30% of cases, including iritis and iridocyclitis. The most common manifestation is granulomatous nodules in the iris. Involvement of the lacrimal glands results in painless nodular swelling, often accompanied by cervical lymphadenopathy, and may also affect the submandibular, salivary, and parotid glands (Mikulicz syndrome). Conjunctivitis, keratitis, retinitis, and optic nerve damage can also occur, potentially leading to blindness.
(3) Pulmonary Damage: Lung involvement is relatively common. X-ray examination reveals punctate, linear, or patchy shadows. Hilar lymphadenopathy is present. Early clinical symptoms are mild, but imaging findings are particularly pronounced; in the late stage [third stage], pulmonary fibrosis is evident.
(4) Bone and Joints: Swelling and pain in the finger and toe joints, with X-ray examination showing spongy cavities. These cystic lesions are mostly composed of epithelioid cell clusters, similar to the lesions seen in the skin.
(5) Liver: Approximately 20% of patients have liver involvement. Main manifestations include liver nodules, hepatomegaly, elevated serum alkaline phosphatase, gallstone-induced cirrhosis, and portal hypertension.
(6) Heart: Common manifestations include tachycardia, arrhythmia, atrioventricular block, pulmonary hypertension, and heart failure.
(7) Kidneys: Due to increased blood calcium and urinary calcium, kidney stones or sarcoid glomerulonephritis may occur, leading to renal failure.
(8) Nervous System: Both the central and peripheral nervous systems can be affected.
bubble_chart Auxiliary Examination
Sarcoidosis is a systemic disease, with most patients experiencing anemia, decreased white blood cells and platelets in the blood, and increased eosinophils. During the acute phase, the erythrocyte sedimentation rate increases, and in the chronic phase, serum globulins are elevated. The increase in α-2, β, and γ globulins is particularly noticeable. When there is liver or bone damage, serum alkaline phosphatase often increases. The cephalin flocculation test is usually positive. Hypercalcemia occurs in one-third of cases.
1. The subcutaneous node tuberculin test is mostly negative or weakly positive.
2. Angiotensin-converting enzyme (ACE) measurement: Lieberman noted that serum ACE levels are significantly elevated in patients with active sarcoidosis. ACE is a membrane-bound glycoprotein found in the endothelial cells of lung capillaries, which converts angiotensin I to angiotensin II, which has a pressor effect, thereby increasing blood pressure.
3. X-ray examination: Hilar lymph nodes are often enlarged, showing characteristic changes in the lungs. Lung markings are thickened, with punctate and nodular shadows. Spongy cavitary lesions can be seen in the distal phalanges.
4. Kveim test: This is a specific cellular immune abnormality reaction. The method is as follows: Under sterile conditions, the tissue of a sarcoidosis lymph node is mashed, diluted with saline to a 1:10 concentration, filtered through gauze, and the filtrate is detoxified at 60°C for two hours. After aerobic and anaerobic culture and guinea pig inoculation to confirm sterility, an equal amount of phenol saline is added to dilute into an antigen containing 0.25% phenol. For the test, 0.1 to 0.2 ml of the antigen is injected intradermally on the inner forearm. Six weeks later, a skin biopsy is performed at the injection site. If typical sarcoidosis pathological changes are present, the test is positive. The positive rate of the Kveim test in sarcoidosis patients is over 90%. The false positive rate in healthy individuals and other patients is very low, only 6.5%, making this test highly valuable for diagnosis. As the disease remits, this test can turn negative.
In 1981, Battesti proposed a comprehensive diagnostic criterion. According to this criterion, the diagnosis can be accurately improved. However, this criterion is relatively cumbersome. In 1985, the sarcoidosis research group in China proposed a diagnostic criterion that is essentially the same as Battesti's but more focused and easier to grasp in clinical practice. The content is as follows:
1. Clinical Diagnosis of Sarcoidosis
(1) Sarcoidosis is a disease that affects multiple organs and tissues. Its clinical manifestations are diverse. However, subcutaneous node disease, lymphatic system tumors, or other granulomatous diseases should be excluded.
(2) X-ray examination shows enlargement of hilar and mediastinal lymph nodes, which is symmetrical, with or without reticular, patchy, or nodular shadows in the lungs.
(3) Kveim test shows a positive reaction.
(4) Pathological biopsy confirms or is consistent with sarcoidosis.
(5) Hypercalcemia, hypercalciuria, elevated alkaline phosphatase, and increased plasma immunoglobulins.
(6) Increased serum angiotensin-converting enzyme activity.
Among the above criteria, items 2, 3, and 4 are the main basis for diagnosis, while items 1, 5, and 6 are important reference criteria.
2. Pathological Diagnostic Basis
(1) Mainly granulomas formed by epithelioid cells. The nodules are evenly distributed, with consistent morphology and size.
(2) Caseous necrosis does not occur within the nodules, with occasional small foci of fibrinoid necrosis.
(3) Multinucleated giant cells (Langhans cells and foreign body giant cells often coexist) are commonly seen within the nodules, with a small number of lymphocytes scattered within the nodules.
(4) Schaumann bodies or asteroid bodies are occasionally seen within the giant cells.
(5) Acid-fast staining is negative.
(6) Silver staining shows abundant reticular fibers within and around the nodules, while the reticular fibers within the nodules are mostly destroyed.
(7) Thin-walled small blood vessels are sometimes seen within the nodules.
bubble_chart Treatment Measures
The course of the disease is unpredictable, making treatment often difficult to evaluate. Simple skin and lymph node lesions often resolve spontaneously and do not require treatment.
Topical and systemic use of corticosteroids can suppress inflammatory responses, promote lesion absorption, and prevent the spread and chronicity of lesions. The indications for corticosteroid treatment include acute systemic sexually transmitted disease with fever, active eye disease, lung disease, heart disease, hypercalcemia, and central nervous system damage.
For only skin disease lesions or a few nodular lesions, intralesional injection of corticosteroid suspension can produce rapid results.
Isoniazid, streptomycin, BCG, and vitamin D2 have been used, but the effects are not significant. Chloroquine is effective for chronic pulmonary fibrosis and skin disease lesions, but attention should be paid to eye and heart side effects during medication. The effects of immunosuppressants such as methotrexate and azathioprine are unclear. In the treatment of destructive cutaneous sarcoid tumor diseases and sarcoid uveitis, scholars like Vein have pointed out that the combined use of corticosteroids and methotrexate is effective.
The skin diseases that need to be differentiated from sarcoidosis include: lupus vulgaris, subcutaneous nodule-type leprosy, cutaneous leukemia, advanced stage syphilis, morphea, erythema induratum, cutaneous leishmaniasis, granuloma faciale, lupus erythematosus profundus, granuloma annulare, xanthoma tuberosum, polymorphous light eruption, necrobiosis lipoidica, erythema nodosum, lymphocytoma, mycosis fungoides, and reticulohistiocytosis.
The Kveim test and histopathological examination have diagnostic value.
