Pathology Of Pemphigus

BackgroundPemphigus describes a group of chronic and recurrent autoimmune disease with acantholysis of keratinocyte cells. On clinical manifestations, skin and mucous membranes are often affected, which has blisters and bullae. As blisters rupture easily, it may form a wide range of erosive areas with severe patients, then lead to the skin barrier damage, bacterial infection, hypoproteinemia etc. Finally, the patients may die. The incidence of pemphigus is relatively low, but the mortality rate is exceedingly high, which the application of glucocorticoid is decreased significantly. At present, the leading cause of death is not the disease itself, but from the side effects of corticosteroids and immunosuppressive drugs. With its early diagnosis and treatment, it can reduce the dosage of corticosteroids and immunosuppressive drugs and get a better prognosis.The diagnosis of pemphigus is established by the clinical manifestations、histological features and immunofluoresence findings. Direct immunofluorescence examination is the gold standard in confirming pemphigus, but the histopathologic analysis can help classify the clinical subtypes and further make different treatment options. It will have a great significance on studying histopathologic change of pemphigus.The histologic change of pemphigus was appearing acantholysis of keratinocyte cells,then led to intraepidermal blisters and clefts. Previous studies mostly reported the hair follicles acantholytic changes, but the similar changes of sweat glands、sweat ducts、sebaceous glands in domestic and foreign have not been reported. ObjectivesRecord the histologic features of pemphigus patients, and focus on observing skin adnexal acantholytic changes, at last provide new diagnostic evidence. MethodsData was collected of 123 patients who were diagnosed pemphigus in the Inpatient Department of Dermatology, the First Affiliated Hospital, Zhengzhou University from January 1, 2005 to September 31,2015. According to the patients medical information, find out the corresponding slides. The two dermatologists who have rich experience on diagnosis of dermatological pathology have observed slides, multiple times. Record each slide of cleft level(for PV,the cleft level includes above papulary dermis、above basal cell layer、above more than two epidermal cell layer); blister contents; other changes in epidermis; dermis inflammatory infiltrate location and category; other changes in dermis; hair follicules、sebaceous glands、suboriferous、suboriferous ducts involved in slides; and skin adnexal acantholytic changes and other meaningful changes. Both record the patients name, gender, age at admission, disease course at admission, location, mucous member involvement, past medical history, family medical history, maximum steroid dosage, first tapering time, immunosuppressant category and dosage, immunofluorescence, pemphigus types. Statistic and analyse data. Results1. The general situation:in the 123 pemphigus patients, 55 male(44.7%) and 68 female(55.3%)was invovled and the male to female ratio was 1:1.24. Age at admission:range 18 to 87 years old, mean±standard deviation age was 53.05±14.14 years old. Disease course at admission: range 7 days to 12 years, mean±standard deviation time was 10.69±19.60 months. Onset ages: range 18 to 87 years old, mean±standard deviation age was 52.33±14.14 years old.2. Location in the lesion:oral, lip, pharyngeal cavity, tongue, gingiva, palate, labium majus, crissum, conjunctiva, scalp, face, chest, back, arms, hands, armpits, groin, hip, the foreskin and glans penis. In the 123 patients, 45 people(34.15%) was cutaneous-only invovled, 78 people(60.98%) was mucocutaneous invovled, and 7 people(4.87%) was mucosal-only invovled. In total, mucosal lesion was affected 78 patients(63.41%), and oral manifestation was affected in 71 people, which is with 57.72% of the total and 91.03% of the mucosal involvement. Cutaneous lesion distribution are more likely to occur in head and face, trunk, limbs. In personal medical history, 6 people have diabetes mellitus(include 5 type 2 diabetes and 1 type 1 diabetes), 20 people have hypertension, 8 people have cerebrovascular disease, and 2 people have chronic hepatitis B, 1 people has psoriasis, 1 people has nodular goiter, 1 people have hyperthyroidism, 3 people have chronic superficial gastritis, 1 people has intestinal excitation heat syndrome, 1 people has chronic urticaria. In family medical history, there were 1 case of diabetes mellitus, and there were 1 case of hypertension. The rest is no exception.3. The use of glucocorticoid and immunosuppressive agents are as follows:(1) in 123 patients, steroid was applied to 120 people(97.56%). 3 people failed to clearly record the use of glucocorticoid and was excluded, because the patients hospitalized time is short. In 117 cases, the application of glucocorticoid( prednisone dosage) patients were analyzed. The maximum steroid dosage range 37.5mg to 150 mg, mean±standard deviation dosage was 78.34±22.39 mg. the first tapering time range 4 days to 35 days, mean±standard deviation time was 13.60±6.44 days, dosage at delivery range 30 mg to 80 mg, mean± standard deviation dosage was 50.03±12.48 mg.(2)In 123 patients, adjuvant drugs was used as follows:(1)54 people(43.90%) used immunosuppressive drugs. In affected patients, 40 people were applied cyclophosphamide(accounting for 35.52% and 74.07% of the total and immunosupprants user respectively)、6 people were applied azathioprinum(4.88% and 11.11%)、1 people was applied mycophenolate mofetil(0.81% and 1.85%)、1 people was applied ciclosporin(0.81% and 1.85%)、1 people was applied methotrexate(0.81% and 1.85%)、8 people were applied tripterigium(6.50% and 14.81%);(2) On the use of anti-inflammatory drugs, 4 people were applied thalidomide(3.25% in total)、2 people were applied hydroxychloroquine(2.44%). Usage and dosage: CTX was used intravenous shock therapy with 400 mg or 600 mg weekly, and it was applied from 1 to 6 times, mostly from 3 to 4 times; AZA was used oral 100 mg to 200 mg per day; MMF was used oral 1.0g per day; CsA was used oral 100 mg to 200 mg per day; thalidomide was used oral 50 mg to 100 mg per day; MTX was used intramuscular 10 mg weekly;hydroxychloroquine was used oral 0.2g to 0.4g per day; tripterigium was used oral 60 mg per day. Collecting pemphigus patients are all adults, so the usage and dosage of drug used in adult.4. In 123 pemphigus patients: PV were 91 people(71.54%), P Veg were 3 people(4.88%), PF were 23 people(6.50%), PE were 3 people(14.63%), IgAP were 3 people(2.44%). Direct immunofluorescence(DIF) result are as follows: IgG(+/±) 12 people, C3(+/±) 12 people, IgG(+/±) and C3(+/±) 98 people, IgA(+) and IgG(+) and C3(+) 3 people, IgA(+) and C3(+) 1 people. In all cases,DIF shows intercellar deposition of keratinocytes.5. The change of histopathologic features are as follow. On cleft level, PV have three situations including above papulary dermis 、above basal cell layer、above more than two epidermal cell layer; PF and PE show blisters and clefts in granular layer. Sometimes we cannot find the corneous layer and granular layer in some slides, and also did not see blister, but there are scattered acantholytic cells, which can help us make a diagnosis. On blisters contents, we can see acantholytic cells with single or assemble mostly; there are lymphocytes, eosinophils and neutrophils, fabrin celluloses appearance with single or mixed. On other changes in epidermis, we can often see vacuoles degeneration above base layer cell in PV; and it also occur spongiform edema commonly; there are with lymphocytes 、 eosinophils and neutrophils infiltration with single or mixed; parakeratosis; dyskeratosis; crusta; it less happen acanthosis and subcorneal pustules. On dermis inflammatory infiltrate location and cell category, we can see focal and shallow inflammatory cells infiltration, which includes lymphocytes、eosinophils and neutrophils single or mixed, sometimes it appears plasmocyte. On other changes in dermis, pigment incontinence commonly happen, and sometimes we can see hemangiectasis.6. On skin adnexal(hair follicles, sebaceous glands, sudoriferous ducts) change, the occurrence of acantholytic change in 123 patients are as follows. The hair follicle involved 35 cases, which is of 10 cases with inflammatory infiltration;sebaceous glands involved 10 cases, which is of 3 cases with inflammatory infiltration;sweat ducts involved 10 cases without accompanying obvious inflammatory infiltration. There are 2 cases appearing perifolicular inflammatory infiltration in intact cutaneous appendages patients.7. Using Spss 22.0 chi-square, PV cleft level in the three locations has statistically difference, because the result are all p=0.000; hair follicles with acantholytic changes more easily accompanied with inflammatory cells infiltration has statistical difference, because the result is p=0.000. Conclusions1. In PV, the cleft he blisters and clefts more easily occur above basal cell layer.2. In PF and PE, the blisters locate in the granular layer; sometimes we cannot see granular layer,but there are scattered acantholytic cells. In epidermis, it often occurs vacuoles degeneration above the base layer cell in PV; and there are also lymphocytes、eosinophils and neutrophils infiltration single or mixed in epidermis; we can always see some spongiform edema. In dermis, it happened focal shallow inflammatory cells infiltration, which includes lymphocytes, eosinophils and neutrophils, single or mixed.3. On skin adnexal, we can find the hair follicles with acantholytic change, besides sebaceous glands and sudoriferous ducts. Hair follicles with acantholytic changes are more easily accompany with inflammatory cells infiltration.