Drug-induced bullous pemphigoid with dermal fluorescence on salt-split skin

The immunological features of drug-induced bullous pemphigoid appear to be similar to those of idiopathic bullous pemphigoid (BP), with presence of circulating and tissue-bound antibodies showing anti-basement membrane zone specificity. We describe a 28-year-old woman who developed a widespread blistering eruption with marked involvement of the mucous membranes shortly after commencing treatment with oral flucloxacillin. The eruption gradually cleared following drug withdrawal and treatment with oral corticosteroids. Indirect immunofluorescence showed circulating IgG anti-basement membrane zone (BMZ) antibody and C3 which bound to the dermal aspect of salt-split skin, and direct immunofluorescence (IMF) of perilesional skin showed a linear band of C3 at the BMZ. Western immunoblotting of the patient's serum showed positive reactivity with a 180 kDa antigen in epidermal extracts and no reactivity with dermal extracts. The dermal-binding pattern on indirect IMF with salt-split skin only occurs in a minority of patients with BP and has not been described previously in a drug-induced case.     

Detection of Autoantibody against 97-kD Antigen by Immunoblot,but not by Indirect Immunofluorescence,in a Patient with Linear IgA Bullous Dermatosis

A case of linear IgA bullous dermatosis in an 85-year-old man is reported. Direct immunofluorescence (IF) of the lesional skin showed linear deposition of IgA and weak deposition of IgG at the basement membrane zone. Although no circulating autoantibody was detected by indirect IF, immunoblotting analysis using NaCl-separated normal human epidermal extracts revealed a circulating IgA antibody which bound to the 97-kD antigen.     

Ultrastructural aspects of infiltrated eosinophils in bullous pemphigoid.

By scanning (SEM) and transmission electron microscopy (TEM), we evaluated the infiltrated eosinophils in lesions at various stages of clinical development from patients with bullous pemphigoid (BP) and eosinophilia. Visualized by SEM, numerous inflammatory cells migrated through the cutaneous basement membrane into the cavity of newly formed blisters 12 to 24 hrs after formation. Many migrating cells attached to the reverse side of the bullous cavity, and some basal cells shed into the cavity. As the bullae developed 24 to 48 hrs after formation, the reverse surface of the bullous cavity became predominantly composed of these migrating cells and the exposed squamous cells. The migrating cells had villi, ruffles and ridge-like profiles on their surfaces, which were suggested eosinophils. By TEM in the same lesions, many morphologically activated eosinophils were seen to have passed through the basement membrane into the newly formed blisters; they exhibited spheroidal cytoplasmic granules with less dense crystalloid cores and intracellular channels. Eosinophils infiltrating in the developed bullous cavity directly adhered to basal cells and released their granule contents onto these target cells. These findings suggest that inflammatory cells, especially eosinophils, may amplify the formation of dermal-epidermal separation in BP lesions.     

Effect of Nonenzymatic Glycosylation on the Titers of Circulating Autoantibodies in Pemphigus and Pemphigoid

Hyperglycemia is observed in some patients with autoimmune bullous diseases complicated by diabetes mellitus or treated with systemic corticosteroids. High concentrations of glucose can react with various proteins and change their structural and functional properties. We previously reported that nonenzymatic glycosylation of antibody can impair antigen-antibody binding. We ascertained whether glycosylation of autoantibody decreases the autoantibody titer by examining 30 sera from patients with pemphigus and pemphigoid. Nonenzymatic glycosylation in the physiological range was induced by incubation of sera with 1650 mM D-glucose at 4°C for 7 days. The titers of sera were determined by indirect immunofluorescence (IIF). In all cases, the immunofluorescence intensity of glycosylated sera was weaker than that of nonglycosylated sera. Glycosylated sera showed a lower antibody titer by 1 doubling dilution in 18 out of 30 cases, compared with nonglycosylated sera. The ten BP patients' sera were also analyzed by immunoblotting for reactivity with the BP180-GST fusion proteins, SΔ1 and 4575. All BP sera reacted with SΔ1, and 5 out of 10 BP sera reacted with both SΔ1 and 4575. In all the sera that reacted only with SΔ1, the glycosylated sera showed a 1 doubling dilution decrease in autoantibody titer. Interestingly, in 4 out of 5 sera that reacted with both SΔ1 and 4575, there were no differences in the antibody titer between glycosylated and nonglycosylated sera. These results indicate the possibility of a false decrease in autoantibody titers of sera from patients with autoimmune bullous diseases complicated with hyperglycemia. Although the false decrease in titers of autoantibodies induced by nonenzymatic glycosylation is not dramatic, it must be considered in order not to underestimate the disease activity of pemphigus in such cases.     

Topical retinoid treatment for various dry-eye disorders

We evaluated the clinical efficacy of treating various dry-eye disorders using 0.01% and 0.1% (weight/weight) topical all-trans retinoic acid ointment. Twenty-two patients were selected and classified into four major groups: keratoconjunctivitis sicca (6 patients; 11 eyes), Stevens-Johnson syndrome (9 patients; 17 eyes), ocular pemphigoid or drug-induced pseudopemphigoid (3 patients; 6 eyes), and surgery or radiation-induced dry eye (4 patients; 4 eyes), based on the criterion that they remained symptomatic even under maximum tolerable conventional medical and/or surgical therapies. The results indicated that squamous metaplasia with mucin deficiency secondary to goblet cell loss and keratinization may be the basis for the development of clinical symptoms and morbidities, as these epithelial abnormalities were invariably present before treatment. After treatment, all patients demonstrated clinical improvements in symptoms, visual acuity, rose Bengal staining, or Schirmer test. Most importantly, this topical vitamin A treatment caused the reversal of squamous metaplasia as evidenced by impression cytology. Therefore, this treatment may represent the first nonsurgical attempt to treat these disorders by reversing diseased ocular surface epithelium.     

Acid hydrolases in experimental and spontaneous bullae

Summary The activities of eight acid hydrolases have been measured in blister fluid from various bullous disorders and from experimental suction blisters. The levels of all enzymes increased dramatically for at least 24 h after induction of the blister. No correlation was found between acid hydrolase activity and any individual disease. The levels of activity in spontaneous bullae were similar to those reached after 24 h in experimental suction blisters which had been raised on previously inflamed skin.We conclude that the release of acid hydrolases may be a consequence rather than the cause of blister formation. This conclusion is supported by the lack of inflammatory response to the i.c. injection of blister fluid into normal skin.     

Conjunctival mucoepidermoid carcinoma in a patient with ocular cicatricial pemphigoid and a review of the literature

Invasive mucoepidermoid carcinoma of the conjunctiva of the left lower eyelid was diagnosed in an orbital exenteration specimen of a 57-year-old woman, after a biopsy of the same lesion was originally diagnosed as invasive squamous cell carcinoma. The woman was undergoing mitomycin C injections for ocular cicatricial pemphigoid, diagnosed in the same eye 2 years prior to identification of the neoplasm. The tumor invaded the cornea, sclera, lacrimal gland, regional small nerves, and lymphatics, but did not show intraocular involvement. The original biopsy specimen was reassessed with stains for mucin and found to be mucoepidermoid carcinoma of the conjunctiva. We reviewed 21 cases of mucoepidermoid carcinoma of the conjunctiva described to date in the English literature. We believe this number underestimates the true incidence of this condition, as it is frequently misdiagnosed both clinically and histopathologically. Evaluating suspected aggressive squamous cell carcinoma with special stains for mucin generally helps to identify mucoepidermoid carcinoma of the conjunctiva. More extensive surgical excision than that used for squamous cell carcinoma should be implemented in the management of mucoepidermoid carcinoma of the conjunctiva to prevent recurrence.     

Periodontal status in oral mucous membrane pemphigoid: initial results of a case‐control study

Oral Diseases (2010) 17 , 90–94 Objective: To evaluate the periodontal status of mucous membrane pemphigoid (MMP) patients and compare it with that of healthy controls. Methods: A prospective study was undertaken to examine the impact of gingival MMP lesions on the human periodontium of 29 patients. Parameters evaluated included full mouth plaque score (FMPS), full mouth bleeding upon probing scores, probing depths (PD), gingival recession, clinical attachment level (CAL), mobility score, furcation involvement, number of missing teeth and Machtei criteria. Results: All periodontal parameters recorded were increased in cases when compared to controls in univariate statistics. The mean differences between groups in PD (0.8 ± 0.2 mm, 95% CI 0.3–1.3), CAL (1.3 ± 0.4 mm, 95% CI 0.4–2.2), FMPS (41.0 ± 6.2%, 95% CI 28.7–53.4), FMBS (16.2 ± 6.6%, 95% CI 3.0–29.4) and tooth loss (2 ± 1 teeth, 95% CI 1–3) were all statistically significant (P < 0.01 for all). Substantial differences in domiciliary oral hygiene routines were observed (P < 0.0001). In multivariate models when FMPS was included as covariate the difference between groups in all clinical periodontal parameters was no longer statistically significant. Conclusions: Our results showed that periodontal status is worse in MMP patients if compared with healthy controls due to a substantial difference in oral hygiene. Oral health should be promoted in MMP.     

Ocular Cicatricial Pemphigoid: A Review of Clinical Features,Immunopathology, Differential Diagnosis,and Current Management

Ocular cicatricial pemphigoid is a devastating autoimmune blistering disorder mainly affecting the conjunctiva but frequently associated with systemic mucosal findings. This article is an update of the pathogenesis, ocular findings, differential diagnosis, and approaches to treatment.