OVERVIEW
Benign lymphocytic angiitis and granulomatosis (BLAG) was proposed in 1977 by Saldana et al. It is a disease similar to Wegener’s granulomatosis and lymphomatoid granulomatosis, in which lesions are present in the skin and respiratory tract, and cutaneous lesions are mainly characterized by chronic recurrent seborrheic inflammation. The incidence of the disease has been reported to be low in the national and international literature over the past 20 years, and there is no clear geographical or seasonal distribution. The disease is benign and has a favorable prognosis, with no survivors after treatment and long-term follow-up.
Etiology
The cause of the disease is unknown.
Symptoms
The disease is more common in males, and the age of onset ranges from 31 to 74 years, with an average of 57 years. The damage and course of most typical cases is similar to that of acute pox-like mossy furuncles, except that the lesions are larger, fewer in number, and have a greater tendency to become necrotic. The primary lesion is a red papule, up to about 1 cm in diameter, which may progress to papular blistering, papular pustular or hemorrhagic, with surface necrosis after several days and weeks. Typical damage may heal spontaneously within 8 weeks. Most tend to be chronic, and without treatment, new damage continues to appear, so that lesions from different periods can coexist. The damage heals with acne-like, hyperpigmented or hypopigmented scarring. Self-conscious symptoms are mild. 10% to 20% of patients with lymphomatoid papulosis may develop CD30 cutaneous T-cell lymphoma or Hodgkin’s disease. In addition to cutaneous lesions, extrapulmonary invasion is rare. Patients do not have specific clinical manifestations, initially there is generalized malaise, followed by fever, cough, chest tightness and other symptoms, hemoptysis is rarer than other granulomatous diseases, 80% of the cases in the chest radiographs of the lungs can be seen in varying sizes of multiple nodular shadows, about 20% of the cases in the chest radiographs of the isolated nodules or infiltrative foci, and in some cases can be seen in the cavitary changes; the patient’s blood sedimentation rate (ESR), C-reactive protein (CRP) Blood sedimentation (ESR), C-reactive protein (CRP) and serum immunoglobulin may be elevated, and in some cases the blood is positive for anti-neutrophil cytoplasmic antibodies (ANCA), which are similar to those of Wegener’s granuloma and belong to the C-ANCA category.
Examination
Histopathologic examination: histology has diagnostic value for this disease. The dermis shows wedge-shaped, patchy or perivascular infiltration. Larger damage infiltrates may occupy the entire dermis. The infiltrate may involve the epidermis with inflammatory cells pro-epidermal. Epidermal necrosis and erosion may occur as the damage progresses. Fibrin deposits are seen in the dermal vasculature, and lymphocytic vasculitis is occasionally seen. The dermal infiltrating cells consist of lymphocytes, eosinophilic leukocytes and neutrophils and larger monocytes. Atypical large or small lymphoid cells can be seen, accounting for more than 50% of the infiltrating cells. Histologically the damage can be divided into two types, type A and type B.
Diagnosis
Based on clinical manifestations, lesion characteristics, histopathological features, immunohistochemical examination, etc. The definitive diagnosis of BLAG relies on lung biopsy, and pathological examination reveals the loss of alveolar structures with ill-defined granulomas, vasculitis is characterized by vasculature-centered and invasive cellular infiltrative damage of blood vessels, and the infiltrative cells include normal lymphocytes, plasma cells, histiocytes, anomalous lymphocyte-like and plasma cell-like cells, reticulocytes, and heteromorphous cells. endothelial cells, the morphology of the heterogeneous cells is mitotic, the same as lymphoproliferative disorders, and occasionally large lymphocytes are seen. Some small blood vessels may be obstructed by lymphocyte infiltration, resulting in localized pulmonary embolism and necrosis, but this is rare.
Differential diagnosis
The disease needs to be differentiated from lymphomatoid granulomas and Wegener’s granulomatosis, with the lack of necrotic changes being the main point of differentiation from Wegener’s granulomas.
Treatment
No treatment is usually required. There is no evidence that treatment prevents the development of secondary lymphoma. The treatment of BLAG is similar to that of other granulomatous diseases, i.e., a combination of immunosuppressants and glucocorticoids is required, but the difference is that with this type of treatment, the patient can achieve a one-time recovery and does not require repeated treatment. It is reported that a group of cases with 11 to 24 years of follow-up after treatment had normal survival and no further attacks of disease.
(i) Symptomatic treatment
Symptomatic treatment for BLAG patients is often directed at the management of comorbidities, such as hemoptysis, infection, cough, dyspnea, etc. The following are some examples of symptomatic treatment for BLAG patients
1. Hemoptysis
Hemoptysis in BLAG patients is rare, generally belongs to medium or small amount of hemoptysis, clinic can apply phenolsulfonyl ethylamine, aminomethylbenzoic acid, tranexamic acid added to glucose solution for drip, also can be injected intramuscularly with carbacillin and K vitamins, in severe cases can be injected with drip and/or intramuscularly with bacitracin, generally do not need to apply post-pituitary hormone and transfusion of fresh whole blood; naturally, the efficacy of above treatment is better when applying immunosuppressant and hormone during treatment of the primary pathology. Naturally, the above treatment is more effective when immunosuppressive drugs and hormones are applied in the course of treatment of the primary disease.
2. Pulmonary infection
Lung infections are common in patients with BLAG, especially when cytotoxic drugs and hormones are used, and some cases are hospitalized because of symptoms of infection. Infections are mostly socially acquired at the time of admission, and with the application of treatment for BLAG, the infections gradually turn into nosocomial-acquired bacterial or fungal infections. The treatment of infections should follow the principle of stepwise drug administration, and broad-spectrum antibiotics should be chosen when the pathogenic bacteria are not yet known, and once the pathogenic bacteria have been identified, targeted antibiotics or antifungals should be chosen based on the results of the sensitivity test.
(ii) Targeted treatment
Targeted treatment of BLAG has gone through a process of exploration. At first, according to the treatment experience of interstitial lung disease, pure application of prednisone and other hormone therapy, the condition can be relieved but not cured, and easy to repeat, with many side effects. Later, according to its pathological characteristics, it was treated with anti-tumor cytotoxic drugs such as nitrogen mustard phenylbutyrate and azathioprine, which achieved good results and was designated as the basic treatment of BLAG. The current treatment includes the following.
1. Mild and moderate cases
Oral cellular immunosuppressants alone are sufficient, mainly alkylating agents.
(1) Nitrogen mustard phenylbutyrate Commercial name of tumor canning (LEUKERAN) This product has high selective inhibitory effect on lymphatic tissues, the use of methods: oral: 1h before breakfast or 2h after dinner, continue to take until the efficacy of the emergence of 1 week after the beginning of the reduction of the amount of this process takes about 1 ~ 3 months.
(2) Azathioprine Usually not used as the drug of choice, used when the patient cannot tolerate azathioprine phenylbutyrate or cannot be controlled by corticosteroids alone. Usage: Oral, change to maintenance dosage after 1 to 3 months of continuous use, and maintain treatment for 6 to 12 months.
2. Moderate and severe cases
Combination of immunosuppressant and corticosteroid is needed. The commonly used combination is cyclophosphamide and prednisone. Usage is as follows:
(1) Cyclophosphamide should be administered orally for 3 to 6 months. After remission, the treatment should be maintained until 1 year, and the dose should be reduced by 25mg every 2-3 months.
(2) Prednisone Oral, after the effect should be reduced every month to 6 months.
(3) Maintenance therapy Maintenance therapy for patients intolerant to cyclophosphamide can be changed to azathioprine and prednisone for 6 to 12 months.
Prognosis
Typical damage may heal spontaneously within 8 weeks. Pox-like, hyperpigmented or hypopigmented scarring remains after the damage heals.