Epidermolysis Bullosa Acquisita Occuring In A Patient With Systemic Lupus Erythematosus

Epidermolysis Bullosa Acquisita (EBA) is a rare, chronic autoimmune subepidermal bullous disease and has been noted to be associated with systemic lupus erythematosus (SLE). The incidence of EBA and SLE in one patient within the period of 1980-1990 found only 7 published case reports. A 23 years old woman with exfoliate skin since 12 years ago. Initially itchy on her buttock then appeared small blister. Blister spread almost the entire body and rupture. This complaint got worsening in a year accompanied with hair loss, weight loss, and oral ulcer. Dermatological examination showed patch eritematosa, hyperpigmentation, hypopigmentation, erotion with erythematous base, yellow brownish crust. Also obtained sclerodactyli toes and nail fingers. Laboratory examination anemia gravis, hypoalbuminemia, Coombs test +2, ANA Test negatif, dsDNA IgG 32,80. Histopathology examination showed blister subepidermal, no vacuolar degeneration, no superficial and deep infiltrat, and minimal lymphocyte. Patient had diagnosed SLE from Internal Department based on MEX-SLEDAI score.The patient was treated with metylprednisolone intravenous pulse dose 500 mg on 3 days then tappering off and wound care. Epidermolysis Bullosa Acquisita immunogenetically related with MHC class II haplotype in particular HLA-DR2. This factor suggest playing role in the development of EBA to express more aggresive SLE.


INTRODUCTION
Epidermolysis Bullosa Acquisita is a chronic, subepidermal blistering disease associated with autoimmunity to the collagen (type VII collagen) and that usually begin in adulthood . Theincidence of approximately 0.2 new cases permillion people. On a case report basis, EBA has been noted to be associated with some of the other autoimmune disease like systemic lupus erythematosus (Ludwig, 2013). Systemic lupus erythematous (SLE) is a chronic autoimmune diseaseaffecting heart, lungs, blood vessels, skin, joints, blood and kidneys (Ganapathy et al., 2017). The incidence of 2 types of autoimmune diseases of EBA and SLE in one patient is still very rare. From some case report within the period of 1980-1990 only got about 7 cases have been reported worldwide by Dotson et al., 1981, Gammon et al., 1985and Boh Erin et al., 1990 Therapy for EBA and SLE patients is unpredictable and still needs challanges. Systemic corticosteroid still be the first choice for both EBA and SLE (Badsha and Edward 2003;Ishii et al., 2010). Especially supportive therapy is necessary for all EBA patients to help reduce the risk of complications and improve the quality of life. This includes proper wound care and strategies for avoiding trauma (Gupta et al., 2012). An EBA case was reported in a 23 year old woman with severe SLE. Patient got therapy methylprednisolone injection pulse dose and followed with methylprednisolone oral with tappering off and wound care.

CASE
A 23 year old woman referral from Ngudi Waluyo Hospital to the emergency room dr.Saiful Anwar general hospital with chief complaint exfoliate skin since 12 years ago. Initially there were itchy on her buttock then appeared small blister. That blister and formed pink area and wet. Then many other blister appeared and spread throught the thigh, chest, stomach, back, arm and leg. Almost the area of the body are involved except face area. Patient also complaint in the past 12 years fingers and toes become stiff and gradually tapers fingertips. About 1 year ago, patient complaint itchy and appear blister in her face. Initially in her forehead and spread to the cheek and History of the same complaint, history of malar rash, history of skin rash or scald when exposed to sunlight was denied. Patient got menarche at 20 years old and only lasts for a year. No family history of the same complaint.
Eyes examination of conjunctival anemis. Thorax and abdomen within normal limit. Examination of the extremities of the palms and soles appear pale and there is sclerodactili on the fingers and toes. No enlargement of lymphonodi colli and inguinal, while lymphonodi axillae is hard to evaluate because there are some wound. The patient current weight is 25 kg.
Dermatological examination on facialis obtained hyperpigmented and hypopigmented macules and patches, multiple, irregular shaped, varied in size. Scalp area with alopecia areata and thin whittish scales. Almost the entire body obtained patch erythematousa, patch hyperpigmented, well defined, irreguler, varied in size and erosion with erithematous base (+), brownish crust (+).
There is no appear pubic hair in the patient's genital area.
Follow up at the 18 th day in the outpatient dermatovenereology obtained clinical improvement with minimal erosion. Treatment followed with methylprednisolone oral 3x16 mg, lansoprazole oral 0-0-1, chloroquine oral 1x250 mg, and gentamicine cream. people (Ludwig, 2013). On the other hand, the annual incidence of SLE which is also a kind of autoimune disease is estimated to be 6.4-7.6 cases per 100,000, whereas, approximately one case per 2,000 Caucasians are reported. Systemic Lupus Erythematosus occurs more commonly in females (15-45 years) than males in the ratio of 9-10:1. The etiopathogenesis of SLE is associated with several genetic factors (HLA-DR2 and HLA-DR3; C4a and C4b, C1q, C1r/s and C2 (complement consumption and immune complex deposition) (Ganapathy et al.,2017). The same immunogenetic background related with particular HLA-DR2 between EBA and SLE that will contribute to the develpoment of EBA to express a more aggressive SLE and vice versa.
Several criteria have been established for EBA diagnosis : (1) onset in adulthood, (2)absence of a family history of the disease, (3) clinicallesions consisting of bullae produced by trauma, milia,atrophie scars, and nail dystrophy, and (4) exclusion oflichen planus, erythema multiforme, lupus erythematosus (LE), and bullous drug eruption ( Dotson et al.,1981). Dotson et al.,1981 have been reported a SLE case in patient with EBA in 19 year old woman, where is initially appear lession of blister accompanied by itching starting at the age of 13 years.Boh Ering et al.,1990 also report three patients with EBA in whom SLE subsequently developed.
Histopathology examination from lession in the right thigh with punch biopsy methode obtained sub epidermal blister, no vacuolar degeneration, no superficial and deep infiltrat, and only minimal lymphocytes. Subepidermal blister is appropriate with one of the criteria from Dotson et al.,1981 in support EBA. Another criterion that has been met is the onset of of disease beginning at the age of 12 years, no history of the same disease in family, blister that ruptured leaving trauma, milia, and there is nail distrophic. The lession that present in patient start from the trauma area of the gluteus/sacrum and are not limited to sun exposed areas only.  (Badsha and Edward 2003;Ishii et al., 2010). Methylprednisolone injection intravenous pulse dose 500 mg for 3 days are said to have significant anti-inflammatory and immunosuppressive effects which will be effective in generating shorter remission periods in both EBA and severe SLE patient (Badsha and Edward 2003;Ishii et al., 2010;Kim and Kim 2011).
Other therapies that can support patient's clinical improvement are extensive erosion treatment in patients. This wound care can prevent other more serious infections (Gupta et al.,2012). To date, there are no specific wound care guidelines or any evidence that address the wound care challenges of the EBA population, but in a report by Pope et al., 2012 mentioned some recommendations of wound care for EBA patient there are nutrition management for patient with low intake or got hypoalbumine, management for maintain haemoglobin level above 8 mg/dL, gentle cleansing wound with a saline solution, topical antibiotics short term and rotated every 6 weeks to prevent resistance (Pope et al.,2012).

CONCLUSION
There have been reported cases of EBA in 23 year old woman with severe SLE.
Enforcement of EBA diagnosis based on onset that occurs from adulthood, no family history of the same disease, clinicallesions consisting of bullae produced by trauma, milia, atrophie scars, and nail dystrophy. Subepidermal blister from histopathology examination is appropriate with one of the criteria. While the diagnose of severe SLE based on MEX-SLEDAI criteria. Patient got therapy methylprednisolone intravenous pulse dose for 3 days with tappering off and wound care. Clinical improvement was obtained on the 18 th day of treatment. There are few reports in the literature describing classical EBA in patient with SLE. Finding in this patient add further support to the suggestion that EBA occuring in association with SLE.