Dermatosclerotic diseases Dermatosclerosis refers to the limited or diffuse skin tissue hardness increase, tightening and elasticity decrease caused by dermal collagen fiber proliferation and cell infiltration, dermal or subcutaneous edema and other skin changes; and dermatosclerotic diseases refer to a group of diseases characterized by skin sclerosis including various etiologies. The diseases that can cause scleroderma-like lesions are classified according to the etiology as follows. Immune abnormalities (a) Systemic scleroderma: a systemic disease that can involve the skin, digestive tract, lungs, heart and kidneys. The lesions can be broadly divided into edematous, sclerotic and atrophic phases. According to the degree of skin involvement and vascular changes, the disease can be divided into two types: acral sclerosis (95% of cases) and diffuse scleroderma (5% of cases). There are also subtypes of CREST syndrome. The increased rate of collagen synthesis in fibroblasts in this disease may be due to the presence of a subpopulation of fibroblasts with high collagen production, and damage to capillary endothelial cells may also be a primary factor causing fibrosis; about 20-30% of patients have a highly specific marker antibody, SCL-70 antibody (up to 60% in the diffuse type), and 24% have anti-synaptic antibodies ( CREST syndrome has a positive rate of 49-96%), and anti-nucleolus antibodies may be present in diffuse patients. These three more specific antibodies help to classify and determine the prognosis. (B) Eosinophilic fasciitis: first reported by Shulman in 1974. It occurs in the forearm and lower leg, with tension edema followed by sclerosis, consolidation of the underlying tissue, and hypertrophy of the skin and subcutaneous tissue, manifesting as nodular or scleroderma-like plaques. The large veins and tendon areas may show obvious striated furrow-like depressions, and the skin of the upper extremities may have an orange peel-like appearance. The face and fingers (toes) are rarely invaded, often without Raynaud’s phenomenon, and the internal organs are generally not invaded, with a slow course and good prognosis. Laboratory tests include hypergammaglobulinemia and increased eosinophilia in the peripheral blood. Histopathological changes in the skin are mainly in the deep fascia, showing diffuse fascial thickening with eosinophil and lymphocyte infiltration. (C) Dermatomyositis: It is a diffuse inflammatory disease of the skin and muscles. The skin develops edematous erythema and the muscles develop inflammatory degeneration resulting in weakness and pain. About 10% of patients can develop sclerotic changes in the skin 6 months to 3 years after the disease, called sclerosing dermatomyositis. (iv) Mixed connective tissue disease: first reported by Sharp et al. in 1972, with clinical features of SLE, systemic scleroderma and dermatomyositis at the same time. Typical clinical signs include Raynaud’s phenomenon, polyarthropathy, sausage-like swelling of the hands, finger sclerosis, decreased esophageal motility, and pulmonary hypertension. Laboratory features include high titers of anti-RNP antibodies in the serum and direct immunofluorescence tests showing patchy (or granular) deposits of IgG in the nuclei of epidermal cells. (v) Graft-versus-host disease: a disease caused by an inter-tissue reaction between immunoreactive cells in the transplanted tissue and an immunosuppressed, histologically incompatible antigen recipient. The skin is the primary target organ, and its clinical manifestations may include early flat moss-like lesions followed by a scleroderma-like rash, mainly on the upper extremities, face, and trunk, with skin changes that are clinically and histologically indistinguishable from scleroderma.DIF shows Ig and complement deposits in the basement membrane and around dermal vessels. Metabolic or endocrine abnormalities (a) Scleroderma: 90-95% of patients start 1-6 weeks after infectious acute fever. The lesions start on the head and neck and eventually involve the extremities, but the hands and feet are not involved. The lesions are hard and shiny, cannot be pinched up, and show non-sunken swelling, which can cause swallowing difficulties and limited joint movement due to swelling. The pathological histological changes are thickening of the dermis, swelling and homogenization of the collagen fibers, widening of the interstitial spaces, which are filled with abundant matrix, and can be confirmed as acidic mucopolysaccharide by histochemical staining. (B) Delayed cutaneous porphyria (PCT): testicular hepatic porphyria, the onset of which is related to alcohol consumption and estrogen use. The lesions are often found on exposed areas, often caused by light and minor trauma, including blisters, increased skin fragility, hairiness, pigmentation, etc. About 1/3 of patients can develop scleroderma-like damage years after the onset of the disease, seen in the skin of the face, neck, scalp, chest and dorsal hands, skin hardening, local loss of fine hair, pigmentation changes are obvious, facial lesions resemble systemic scleroderma. The histopathological changes in the skin are thickened collagen bundles and PAS-positive amylase-resistant material throughout the dermis. The patients had abnormally increased urinary porphyrin excretion and all had liver damage. There is also Turkish toxic porphyria, a PCT-like syndrome occurring in Turkey caused by exposure to the exogenous chemical benzene hexachloride. (C) Sclerosing mucinous edema: It is a special type of mucinous edematous moss. The lesions often involve the dorsum of the fingers, the dorsum of the feet, the extensor side of the limbs, the chest and the face, and the characteristic damage is dome-shaped papules with waxy luster, often centered from the hair follicles, with diffuse infiltration and thickening of the skin under the dense papules, showing scleroderma-like changes, but can move and be pinched up, and severe or advanced patients may have limited bending of the limbs and fingers and toes and difficulty in opening the mouth, clinically resembling systemic scleroderma, but the damage is limited to the skin. Histopathologically, it is characterized by fibroblast proliferation and acidic mucopolysaccharide deposition in the skin. (D) Neonatal sclerosis: A severe subcutaneous fat coagulation disease of the newborn, often developing within the first week of life, starting with hardening of the skin of the cheeks, dorsal calves and buttocks with a wax-like appearance, which can invade the whole body in severe cases. The child may die of hypothermia and weak pulse, often combined with pneumonia, diarrhea, jaundice and sepsis. Histopathological changes show enlarged subcutaneous adipocytes and widened connective tissue gaps between adipose lobules, and needle-like crystals in adipocytes, which appear biflexed under a rotating light microscope. (E) Primary systemic cutaneous amyloidosis: It is caused by amyloid deposition in the interstitium and involves many organs such as the heart, liver, kidney and gastrointestinal tract, often with a giant tongue. Skin lesions account for about 25% of cases, with facial purpura being the most common, others having scattered or fused papules and plaques, and a few patients having hard skin and subcutaneous nodules resembling scleroderma or mucinous edema, with localized redness and hardening when the fingers are affected. Patients have elevated plasma γ-globulin, proliferation of bone marrow plasma cells, and Bence-Jones protein in the urine. (vi) Phenylketonuria: a rare genetic disorder. It is caused by phenylalanine oxidase deficiency, resulting in accumulation of phenylalanine in the blood and the presence of phenylketonate and phenylacetic acid in the urine. Phenylalanine inhibits the tyrosine-tyrosinase reaction, resulting in a decrease in melanin. The clinical manifestation is hair and skin hypopigmentation, eczema easily occurs in the white areas, often allergic to light, and the lesions may show scleroderma-like changes. It is often accompanied by mental retardation. (G) Diabetic sclerosis: due to long-term diabetes can make the neck, upper back and shoulder skin sclerosis thickening, symptoms as sclerosis, but no indentation, even if the diabetes is controlled, the lesions are rarely reduced. In addition, 30% of diabetic patients have partial or mild joint stiffness, 1/3 of which have obvious skin hypertrophy, manifested as salami fingers, skin hypertrophy to the end of the fingers mainly, rarely involving the back of the hand, hard and thick skin can not be pinched, pathological tissue image and scleroderma similar. Environmental factors (a) Occupational skin sclerosis: The most common is limb – bone cortical lysis (vinyl chloride disease) caused by exposure to vinyl chloride, trichloroethylene, polyvinyl chloride, with a triad of clinical symptoms, namely Raynaud’s phenomenon, scleroderma-like skin lesions and osteolytic damage. The manifestations of scleroderma-like skin changes vary from small ivory papules on the wrist and dorsal aspect of the fingers to total adhesion of the skin of the hand with limited movement of the hand, red and sclerotic facial skin, and dissolving damage of the terminal phalanges that shorten the nails. In some patients, the scleroderma-like skin lesions may subside spontaneously after removal from exposure. In addition, long-term exposure to epoxies, silicones, organic solvents, and pesticides can produce similar lesions. (b) Erasmus syndrome: A rare disease of silicosis complicated by scleroderma in which the lungs show signs of fibrosis and the silicosis occurs before the scleroderma. The disease may be associated with reduced cellular immune function due to the cytotoxic effects of carbon dioxide. (iii) Drugs: When treating tumors with bleomycin, in addition to common side effects such as alopecia, stomatitis and nail changes, some rare changes can be seen, both hyperpigmentation and skin sclerosis, the latter manifesting as infiltrative spots, nodules and banding damage on the hands, which can produce gangrene of the fingertips in advanced stages and affect hand function in severe cases. The histological changes resemble scleroderma, and the mechanism of occurrence is related to the ability of bleomycin to stimulate collagen and aminopolysaccharide synthesis. Vitamin K injection can also cause scleroderma-like subcutaneous histoplasmosis (lumbar buttocks), which first appears as a red patch at the injection site and expands, and the damage can fuse at the lumbosacral area on both sides, with gradual infiltration of the subcutaneous tissues, resulting in ivory-colored, limited scleroderma-like damage that adheres to deeper tissues after several months. The tissue picture is one of sclerosis and inflammation of the dermal reticular layer, subcutaneous tissues and fascia. In addition, similar damage can occasionally occur with isoniazid, pentazocine, and carbidopa. There is also human co-drug disease-injected silicone and paraffin-which occurs as an autoimmune reaction. (iii) Toxic epidemic syndrome: a new multisystemic disease prevalent in Spain in 1981 due to ingestion of spoiled and then treated vegetable oil, clinically divided into acute, intermittent and chronic phases, mainly invading the respiratory, cardiovascular, neurological, digestive and hematological systems. Most patients have skin lesions, and in the chronic phase (4-5 months after onset), patients tend to develop scleroderma-like lesions, which are characterized by hard, swollen, wrinkle-free skin or hard, shiny skin, and the onset of the proximal and distal extremities is often simultaneous. Extensive osteoporosis. (iv) Eosinophilia-myalgia syndrome: 1500 cases have been reported, associated with L-tryptophan intake, with severe incapacitating myalgia and peripheral blood eosinophilia. (v) PUVA treatment: Scleroderma-like changes may occur, and histological examination shows ray elastic fiber degenerative changes. Neobiotics (a) Carcinoid syndrome: a malignant endocrine tumor that produces 5-hydroxytryptamine, pancreatic vasopressin, histamine and prostaglandins and causes significant cutaneous, gastrointestinal, respiratory, cardiac and hepatic symptoms. The cutaneous manifestations include paroxysmal vasodilatation, facial capillary dilation and persistent erythema, hyperpigmentation and pellagra-like changes that gradually spread to the whole body, but no Raynaud’s phenomenon or visceral lesions, and the ANA is negative. The histological picture was one of thickened and homogenized collagen fibers, diffuse edema, thickened vessel walls, and perivascular lymphocytic and mast cell infiltration. This may be due to prolonged 5-hydroxytryptophan-induced proliferation of dermal collagen fibers or a major role of pancreatic vasopressin. (B) POEMS syndrome: This disease was first described by Shimpo (1968), and most patients have plasma cell malignant changes. 1982 Bandwish abbreviated the main clinical features of the disease polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes to the disease name, POEMS syndrome. The skin changes include hyperpigmentation, scleroderma-like changes, hemangioma, hirsutism, chytridrosis, hyperhidrosis and nail changes. The incidence of scleroderma-like changes is 77%, which manifests as skin tautness, thickening, swelling, sclerosis of the extremities unable to make a fist, shortening of the tongue tie and Raynaud’s phenomenon. Skin biopsy is consistent with scleroderma-like changes. Congenital (a) Congenital skin heterochromia: an autosomal recessive disorder. It often develops between 3 days and 6 months after birth. Skin symptoms include skin heterochromia, hair loss, hypersensitivity to light, nail dystrophy, sclerosing warty nodules on the extremities and hands and feet, congenital cataracts, bone defects, dental defects and endocrine disorders. (ii) Sclerosing cutaneous heterochromia: patients have extremity sclerosis with reticulopigmentation of the skin, atrophy and capillary dilation. (iii) Werner syndrome: The main clinical manifestations include sclerosing cutaneous heterochromia. Hair graying and hair loss, short stature and elderly appearance, cataract, osteoporosis, hypogonadism and diabetes mellitus. (iv) Limb bone striated hypertrophy: Onset at birth or in adolescence, painful movement restriction of one limb, bone X-ray shows irregular shaped osteosclerotic shadow, while linear scleroderma occurs on the skin of the covered part. (E) thick skin periosteal hyperplasia: there are two types of idiopathic and acquired, the former is autosomal dominant, the latter secondary to lung cancer, symptoms include (1) skin hyperplasia and sclerosis of forearm and lower leg; (2) pestle-like finger-like periosteal hyperplasia of hands and feet; (3) gyrate cranial skin, pathological images show thickened dermis, increased number and size of collagen fibers, fibroblasts and basal masses also increased. (F) stiff skin syndrome, also known as congenital fascial dysplasia: autosomal dominant, first reported by Estenly et al. in 1971, may be a mucopolysaccharidosis, the skin can appear at birth or early infancy limited stiffness, hardness like stone, with limited joint movement or mild hirsutism, skin lesions to the waist and buttocks is the most serious, but the skin of the hands and feet is normal, lesion pathology shows that the dermis has more There is no special treatment for this disease. (a) Limited scleroderma: It is divided into punctate, mottled, linear or band-like and generalized scleroderma. The lesions are usually limited to the skin and the subcutaneous tissue of the lesions, and the underlying muscles may occasionally be invaded, but the internal organs are not involved. (B) Chronic radiation dermatitis: often due to long-term, repeated small doses of radiation exposure or acute radiation dermatitis caused by receiving large doses of radiation. Skin heterochromatosis occurs at the irradiated site after several years of exposure to radiation, accompanied by skin sclerosis, ulcers, and even malignant changes. (c) Kimura disease: It occurs in the area of subauricular glands, with thickened and sclerotic skin, possibly palpable infiltrated nodules, and no conscious symptoms. The histological picture is lymphatic follicle-like structures and marked eosinophilic infiltration in the subcutaneous tissue, increased eosinophils in the peripheral blood, and increased serum IgE. (D) Eosinophilic cellulitis: first reported by Wells in 1971, the clinical symptoms are divided into two stages: similar to acute cellulitis, except that the local temperature is not high and antibiotic treatment is ineffective; from 1 to 3 weeks after the onset of the disease, the local lesions gradually harden or show subcutaneous infiltrative plaques or nodules, similar to scleroderma, and about 6 weeks after the natural fading, without scarring. Histopathological examination of the skin showed significant eosinophilic infiltration of the dermis and inflammatory granulomas with flame-like patterns. The peripheral blood picture showed increased leukocytes and eosinophilia (mature type).