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The Systematic Appearance of a Neutrophilic Skin Disease


Neutrophilic skin disease (ND) is a group of diseases with similar histopathological changes, pathogenesis and treatment methods. Histologically, they are characterized by perivascular and diffuse neutrophil infiltration without any definite infectious factors.Skin lesions may appear in a variety of ways, limited or extensive;Common types include Sweet syndrome, gangrenous pyoderma, leucocele’s disease and subkeratotic pustular disease.It is worth noting that in addition to skin damage, neutrophilic skin diseases also have epidermal aseptic neutrophil infiltration, involving organs including lungs, bone joints, digestive tract, liver, spleen, pancreas, central nervous system, cardiovascular system, etc.


  1. The Systematic Appearance of Lung

In recent years, many literatures have reported that neutrophilic skin diseases combined with lung infiltration, among which, the most common extramutaneous infiltrating organ of pyoderma gangrenous is lung.It has been reported that pyoderma gangrene can lead to tracheobronchial lung disease. The bronchoscopy showed that there were a large number of polypoid nodules from the trachea to the bronchus, and the surface was yellowish and not smooth, which was similar to skin lesions.This biopsy demonstrates inflammatory granule necrosis with a large infiltration of neutrophils.In addition, lung infiltration may also occur with Sweet syndrome. In most cases, lung infiltration occurs simultaneously with Sweet syndrome, with occasional secondary cases of Sweet syndrome.The types of lung damage include bilateral lung infiltration, obstructive bronchiolitis with systemic pneumonia, pleural effusion, etc.Clinical symptoms are often manifested as fever, cough, chest pain;Pulmonary imaging changes into pulmonary nodules, reticular or patchy infiltration;Histopathological features include pulmonary interstitial inflammation, edema, mild fibrosis, and numerous neutrophils infiltrating the alveoli.The diagnosis of Sweet syndrome with pulmonary infiltration is usually based on typical clinical manifestations, histopathological examination, and response to hormone therapy.In addition, pulmonary infiltration, especially pulmonary aneurysms, can also occur in behcet’s disease.In general, both skin lesions and lung infiltration can be relieved in patients with neutrophilic skin disease after glucocorticoid therapy.Most of the deaths are due to respiratory failure and so on.


  1. The Systematic Appearance of Bone

Neutrophilic skin disease may be associated with multifocal aseptic bone disease, known as chronic recurrent multifocal osteomyelitis (CRMO).The occurrence of this disease may be related to the mutation of lipoprotein 2(LPIN2), proline – serine – threonine phosphatase interaction protein 2(pstpip2) gene.CRMO is more common in children, with insipid onset, often manifested as long bone pain, stiffness, swelling, with or without fever;Erythrocyte sedimentation rate slightly increased, the number of white blood cells may be increased.Skin lesions can occur at the same time with bone disease or after bone disease, skin lesions are mostly palmetatarsal pustular disease, pustular psoriasis, can also be seen in the psoriasis vulgaris, severe acne, Sweet syndrome, gangrene pyoderma and so on;CRMO and multicenter aseptic osteomyelitis (SAPHO) belong to the same disease spectrum, and some scholars even believe that CRMO is SAPHO of childhood type.The latter is often affected by anterior chest wall and axial bone, and the affected bone has tenderness, joint swelling and pain, fever, increased white blood cells, accelerated blood sedimentation and other symptoms similar to CRMO.CRMO patients are usually ineffectie to antibiotic therapy, but effectie to glucocorticoid therapy, and need low dose hormone maintenance to prevent recurrence;Some scholars have suggested that patients with CRMO complicated with skin damage can also be treated with tumor necrosis factor inhibitors.


  1. The Systematic Appearance of Joint

Arthritis is also a relatively common systemic manifestation of neutrophils.The incidence is about 15% ~ 62%, usually after the occurrence of neutrophilic skin disease, occasionally before the skin lesions.Neutrophilic skin disease joint damage is common in Sweet syndrome and white plug disease.About a third of the patients with Sweet syndrome experience joint pain, myalgia, or arthritis, the latter of which is asymmetrical, non-aggressive arthritis involving the knee and wrist.Glucocorticoid and tumor necrosis factor alpha inhibitor were effective in treatment.Approximately 50% of the patients with bse also have arthritis, with multiple or single joints, non-invasive, common in the knee, wrist, and ankle joints, and 80% have joint symptoms lasting less than 2 months.In addition, cases have been reported of neutrophilic skin diseases induced by granulocyte colony stimulating factor combined with lipid membrane inflammation/fasciitis, joint pain, local skin swelling, laboratory examination showed erythrocyte sedimentation, elevated c-reactive protein, histopathology showed a large number of neutrophil infiltration in tissues, and prednisone treatment was effective.


  1. The Systematic Appearance of Central Nervous System

In neutrophilic skin diseases, central nervous system infiltration is relatively common in Sweet syndrome and behcet’s disease.Neurological symptoms usually appear later than skin lesions.People with Sweet syndrome combined with central nervous system infiltration may have encephalitis and meningitis, and the clinical manifestations are fever, headache, convulsion, consciousness disorder, eye movement disorder, uveitis, optic disc edema, selective language loss, etc.The lesions are similar to nodular erythema.Cerebrospinal fluid is mainly neutrophilic granulocytosis, negative bacterial culture.Systemic hormone therapy is effective in the treatment of this disease, and some scholars have proposed that dapsone can be used in patients with neurologic Sweet syndrome with the tendency of deterioration.Baise disease neurological involvement is common in men, usually appears in the late course of the disease, indicating poor prognosis, neurological involvement can be manifested as acute meningitis, cranial nerve paralysis, brain stem injury (including dysphagia, strong laugh and cry) and other symptoms.Other cases have been reported that pyoderma gangrenous may also present with central nervous system symptoms such as aphasia and headache.


  1. The Systematic Appearance of Abdominal Organs

The visceral manifestations of neutrophilic skin diseases are often aseptic abscesses, and the common ones are liver abscess, spleen abscess, etc. It may belong to the same disease spectrum as neutrophilic diseases such as gangrenous pyoderma, Sweet syndrome, subkeratotic pustular dermatitis, and persistent erythema of eminence, collectively known as neutrophilic disease.Visceral injury may occur after or at the same time as the skin lesion.Some scholars have investigated 30 cases of aseptic abscess patients, 20% of whom also have neutrophilic skin diseases, most of which are splenic abscesses.Such patients may present as fever, abdominal pain, splenomegaly;Leukocytosis, erythrocyte sedimentation and c-reactive protein were increased, but the culture of splenocentesis bacteria was negative.Hormone combined immunosuppression therapy is effective.The specific mechanism of aseptic splenic abscess is still unclear, but some scholars believe that the mechanism of aseptic liver abscess may be that interleukin-8 (il-8) promotes T cell regulation function, leading to aseptic neutrophil infiltrating skin inflammation, accompanied by aseptic liver abscess.In addition to liver and spleen, aseptic abscess may also occur in kidney, which is manifested as microscopic hematuria and aseptic pyuria. Glucocorticoid therapy is effective.In addition, aseptic abscess can also appear in lymph nodes, pancreas, etc.


  1. The Systematic Appearance of Muscle

Muscle involvement is less common in neutrophils.According to a previous study, among 136 patients with neutrophilic skin diseases, less than 10% had myalgia.When gangrenous pyoderma is associated with muscle involvement, the patient may present with fever, weight loss, myalgia, limb muscle weakness, and skin lesions may present as erythema, pustules, ulcers, and necrosis.Emg indicated myositis. Inflammatory cells infiltrated mainly by neutrophils, muscle structure was damaged, muscle fiber necrosis, and other infections and connective tissue diseases were all negative.Hormone therapy is effective.


  1. The Systematic Appearance of Angiocarpy

Heart involvement with Sweet syndrome is extremely rare.However, some scholars reported that the incidence of cardiovascular infiltration increased the mortality rate of Sweet syndrome from 9% to 40%.Therefore, the cardiovascular involvement of neutrophilic skin diseases is still worthy of attention.Recently, a pregnant woman with Sweet syndrome complicated with neutrophilic pericarditis was reported in the United States. The patient developed chest pain, pericardial friction sound, troponin elevation and other symptoms three days after the skin lesion.Vascular involvement in Sweet syndrome is generally manifested as arteriosclerosis, aortitis, aneurysm and coronary artery occlusion.It is worth noting that arteritis and thoracic aortic aneurysm may occur in patients with neonatal Sweet syndrome.In addition, baise disease also has the manifestation of cardiovascular involvement, which is manifested as coronary angitis, valvular disease, myocarditis and arrhythmia, aneurysm, obstructive arteriopathy, superficial or deep venous thrombosis, etc.ANCA is negative in vasculitis caused by behcet’s disease, and antineutrophil cytoplasmic antibody (ANCA) can be positive, but is not associated with disease activity and may be associated with recurrent thrombosis.


  1. The Systematic Appearance of Eyes

Ocular involvement is the most common manifestation of baise disease, which can be seen in 90% of patients. It is common in men and has severe symptoms, including pain and even blindness.Eye manifestations of Sweet syndrome usually include periocular inflammation, lacrimal gland inflammation, conjunctivitis, scleral inflammation, keratitis, iritis, glaucoma, etc., which are generally treated with oral prednisone.In addition to the above organ systems, the systemic manifestations of neutrophilic skin diseases also involve fallopian tubes, lymph nodes and gastrointestinal tract.The systematic manifestations of neutrophilic skin diseases are extensive and diverse. A comprehensive and in-depth understanding of the systematic manifestations of neutrophilic skin diseases is conducive to the rapid and accurate detection and diagnosis of diseases.When dermatologists encounter skin diseases mainly caused by neutrophil infiltration, they should ask for systematic symptoms and conduct corresponding examinations while excluding infectious factors.

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