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    Cicatricial Pemphigoid in Accompany with Rheumatoid Arthritis:a Case Report

    2010-11-22 02:36:00DiWuLimingZhangandYingJiang
    Chinese Medical Sciences Journal 2010年3期

    Di Wu,Li-ming Zhang,and Ying Jiang*

    1Department of Internal Medicine,2Department of Rheumatology,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences &Peking Union Medical College,Beijing 100730,China

    CICATRICIAL pemphigoid (CP,also known as benign mucous membrane pemphigoid) is a rare chronic autoimmune subepithelial blistering disease,with an incidence of 1 per million,characterized by erosive lesions of mucous membranes and skin that result in scarring.1,2Rheumatoid arthritis(RA) is a symmetric inflammatory arthritis that mainly affects the small joints of hands and feet,with a prevalence of 0.3% in China.3In this case report we described the diagnosis of and treatment for a patient developing CP 18 years after the onset of RA,a combination rarely encountered or reported so far.

    CASE DESCRIPTION

    A 72-year old woman was admitted to our hospital because of polyarthritis,oral ulcers,and bilateral conjunctivitis.Nineteen years before,the patient developed insidious symmetric polyarthritis involving shoulders,proximal interphalangeal and metacarpophalangeal joints,knees,wrists,and elbows.Eight years later,deformities in hand joints developed.The patient had been treated with weekly oral methotrexate (MTX) and the polyarthritis subsided considerably after medication.

    Seven months before admission,the patient noticed painful mucosal erosions and blisters in tongue,palate,and posterior pharyngeal wall,along with recurrent gingivitis.After one month,she began to experience burning,dryness,foreign body sensation,and marked conjunctival erythema in both eyes.Bilateral symblephara occurred in two months(Fig.1).No skin lesions were noticed throughout the course.

    One month before admission,the patient underwent a series of tests at the outpatient clinic.The test results showed an erythrocyte sedimentation rate (ESR) of 72 mm/h (reference range,<20 mm/h) and a rheumatoid factor (RF) level of 156 IU/mL (reference range,<20 IU/mL).The patient was diagnosed as RA and suspected with CP because of the characteristic scarring lesions involving oral mucosa and conjunctivae sparing the skin.Aggressive treatment for CP was prescribed considering the rapid progression of the ocular lesions.Oral cyclosporine A (50 mg three times a day),intravenous cyclophosphamide (cumulative dose,1 g),and oral methylprednisolone in large dose were given in accompany with topical treatment in the eyes with tobramycin and dexamethasone.The patient was later hospitalized for further evaluation and management.

    Figure 1.Bilateral symblephara in a rheumatoid arthritis patient concomitant with cicatricial pemphigoid.

    Upon admission,the physical examination detected oral and ocular lesions corresponding with the symptoms described above,found no skin lesions,ulnar deviation and swan-neck deformity in the digits,obvious joint swelling and tenderness,or other abnormal signs.In the rheumatologic tests ordered after admission,ESR was found down to 33 mm/h,and the levels of serum C-reactive protein,immunoglobulins,and complements were normal.The test results for anti-nuclear antibodies,anti-dsDNA antibodies,anti-neutrophil cytoplasmic antibodies,RF,anti-perinuclear factor,and anti-keratin antibodies were all negative.However,her anti-cyclic citrullinated peptide antibody,a specific antibody in RA,was found at a level of 39 U/mL(reference range,<25 U/mL).Radiographs of her hands,wrists,and left elbow demonstrated osteoporosis and changes consistent with stage III RA.Cancer screening detected no obvious abnormalities.Serum anti-desmoglein 1,anti-desmoglein 3,and anti-BP180 autoantibodies were negative.Biopsy of the mucosal lesion was not performed as it was declined by the patient.

    A joint consultation participated by specialists in dermatology,dentistry,ophthalmology,and rheumatology concluded that the patient’s RA was in late stage but stable,CP could be clinically diagnosed with confidence,and the progression had been halted by previous treatment.Ongoing MTX therapy was continued in the treatment for her RA;as for CP,oral and topical cyclosporine A were used,oral methylprednisolone tapered off over six months,and the topical use of dexamethasone stopped immediately.The patient was advised to keep good oral hygiene.In addition to medication,the ophthalmologist suggested that her symblephara be relieved by surgery,but only after CP was fully controlled,which is usually around 1 year after onset.The possibility of relapse in this patient entails long-term follow-up.

    DISCUSSION

    CP is a chronic and progressive disorder,which rarely mitigates spontaneously.It typically affects elderly people(aged 60-80 years),and more females than males (female to male ratio,1.5∶1-2∶1).The commonly involved sites are oral mucosa (85%),conjunctiva (64%),skin (24%),pharynx (19%),external genitalia (17%),nasal mucosa(15%),larynx (8%),anus (4%),and esophagus (4%).1Desquamative gingivitis,tense blisters,and mucosal erosions are common types of oral lesions.Ocular lesions usually manifest as conjunctivitis progressing to scarring which could lead to trichiasis,symblephara,ankyloblephara,corneal ulceration,and blindness.Other major complications may include supraglottic stenosis,dysphagia,and anal stenosis.Skin lesions,including scattered erosions or blisters,are present in only 25%-35% of patients.2The patient in this report presented with the typical clinical characteristics of CP.

    Ultrastructurally,lesions develop within the epithelial basement membranes (EBM).1,2Circulating anti-EBM autoantibodies can be detected in the sera of some but not all patients.The differentiation of CP from other autoimmune bullous diseases may sometimes require immunopathologic studies and immunoelectron microscopy,when clinical findings are atypical.On the other hand,CP patients with anti-laminin-5 autoantibodies appear to have a high risk of adenocarcinoma that approximates the risk in dermatomyositis patients,and the time between onset of CP and cancer diagnosis is reported to be about a year,4therefore cancer screening was conducted in this case.

    Mild lesions in this disease can be treated with topical glucocorticoids,tacrolimus,or cyclosporine A.Oral administration of dapsone may be effective as well.For severe CP conditions,a combination of systemic glucocorticoids and immunosuppressive drugs is recommended.Intravenous immunoglobulin and etanercept have also produced good results,5providing alternatives in cases where first-line therapy fails.Surgical intervention may exacerbate the disease,1therefore should not be considered until full control by medication.

    The association between CP and RA has been reported in several case series since 1978,6,7the largest to date reported by Olsen et al.7In their report,charts from a period of 26 years were retrospectively analyzed,and 8 patients were found having RA concomitant with ocular CP,including 7 females and 1 male.Those patients developed RA 19 years on average before CP diagnosis.The mechanism underlying this association has not been fully understood yet.Genetic factors,especially class II major histocompatibility complex molecules,may have important effects in it.For instance,both RA and CP have been shown to be strongly associated with HLA-DR4.1,3RA and CP may also be linkedviaan immunologically mediated process.In RA,the abnormal activation of T cells is the initiation of pathogenesis,and in CP,apart from humoral immunity,cellular immunity and cytokines may also play a role,particularly in inducing collagen production and fibrosis.8Further studies on their association might shed some new light on the pathogenesis of both diseases.

    1.Bruch-Gerharz D,Hertl M,Ruzicka T.Mucous membrane pemphigoid:clinical aspects,immunopathological features and therapy.Eur J Dermatol 2007;17:191-200.

    2.Fleming TE,Korman NJ.Cicatricial pemphigoid.J Am Acad Dermatol 2000;43:571-91.

    3.Harris ED Jr,Firestein GS.Clinical features of rheumatoid arthritis.In:Firestein GS,Budd RC,Harris ED,et al,editors.Kelley’s textbook of rheumatology.8th ed.Philadelphia:Saunders;2008 .p.1043-78.

    4.Egan CA,Lazarova Z,Darling TN,et al.Anti-epiligrin cicatricial pemphigoid and relative risk for cancer.Lancet 2001;357:1850-1.

    5.Canizares MJ,Smith DI,Conners MS,et al.Successful treatment of mucous membrane pemphigoid with etanercept in 3 patients.Arch Dermatol 2006;142:1457-61.

    6.Spigel GT,Winkelmann RK.Cicatricial pemphigoid and rheumatoid arthritis.Arch Dermatol 1978;114:415-7.

    7.Olsen KE,Holland EJ.The association between ocular cicatricial pemphigoid and rheumatoid arthritis.Cornea 1998;17:504-7.

    8.Lee SJ,Li Z,Sherman B,et al.Serum levels of tumor necrosis factor-alpha and interleukin-6 in ocular cicatricial pemphigoid.Invest Ophthalmol Vis Sci 1993;34:3522-5.

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