The Second Study of Clinical and Immunological Findings in Anti-laminin 332-Type Mucous Membrane Pemphigoid Examined at Kurume University—Diagnosis Criteria Suggested by Summary of 133 Cases

BackgroundRecently, we published an article retrospectively summarizing the results in 55 anti-laminin 332 (LM332)-type mucous membrane pemphigoid (MMP) cases examined at Kurume University, which were diagnosed by strict inclusion criteria, including positive reactivity in direct immunofluorescence and absence of antibodies to non-LM332 autoantigens. However, indirect immunofluorescence using 1M-NaCl-split normal human skin (ssIIF) is also valuable for diagnosis of anti-LM332-type MMP.MethodsIn this second study, we selected 133 anti-LM332-type MMP cases, which were diagnosed by our different inclusion criteria: (i) immunoglobulin G (IgG) deposition to basement membrane zone (BMZ) by direct immunofluorescence or IgG reactivity with dermal side of split skin by ssIIF, (ii) positivity for at least one of the three subunits of LM332 by immunoblotting of purified human LM332, and (iii) the presence of mucosal lesions. Clinical, histopathological, and immunological findings were summarized and analyzed statistically. Although these cases included the 55 previous cases, the more detailed study for larger scale of patients was conducted for further characterization.ResultsClinically, among the 133 patients, 89% and 43% patients had oral and ocular mucosal lesions, respectively, 71% had cutaneous lesions, and 17% had associated malignancies. Histopathologically, 93% patients showed subepidermal blisters. The sensitivities of ssIIF and direct immunofluorescence are similar but are significantly higher than indirect immunofluorescence using non-split human skin (both p < 0.001). In immunoblotting of purified LM332, patient IgG antibodies most frequently reacted with LMγ2 subunit (58%), followed by LMα3 (49%) and LMβ3 (36%). Thirty-four percent patients recognized additional non-LM332 autoantigens. Statistical analysis revealed that autoantibodies against non-LM332 autoantigens might stimulate the production of anti-LMγ2 antibodies.ConclusionsThis retrospective study further characterized in more detail the clinical and immunological features of 133 cases of anti-LM332-type MMP, in which the new diagnostic criteria without positive direct immunofluorescence reactivity were useful for the diagnosis. Higher frequency with anti-LMγ2 antibodies suggested more significant pathogenic role of this subunit. Additional autoantibodies to non-LM332 autoantigens detected in one-third of the patients may contribute to complexity in anti-LM332-type MMP, including the induction of anti-LMγ2 antibodies.

Comparison of Two Diagnostic Assays for Anti-Laminin 332 Mucous Membrane Pemphigoid

Anti-laminin 332 mucous membrane pemphigoid (MMP) is an autoimmune blistering disease characterized by predominant mucosal lesions and autoantibodies against laminin 332. The exact diagnosis of anti-laminin 332 MMP is important since nearly 30% of patients develop solid cancers. This study compared two independently developed diagnostic indirect immunofluorescence (IF) tests based on recombinant laminin 332 expressed in HEK239 cells (biochip mosaic assay) and the migration trails of cultured keratinocytes rich in laminin 332 (footprint assay). The sera of 54 anti-laminin 332 MMP, 35 non-anti-laminin 332 MMP, and 30 pemphigus vulgaris patients as well as 20 healthy blood donors were analyzed blindly and independently. Fifty-two of 54 and 54/54 anti-laminin 332 MMP sera were positive in the biochip mosaic and the footprint assay, respectively. In the 35 non-anti-laminin 332 MMP sera, 3 were positive in both tests and 4 others showed weak reactivity in the footprint assay. In conclusion, both assays are easy to perform, highly sensitive, and specific, which will further facilitate the diagnosis of anti-laminin 332 MMP.

Oral Pemphigoid Recalcitrant Lesion Treated with PRGF Infiltration. Case Report

Mucous membrane pemphigoid (MMP) is a heterogeneous group of chronic autoimmune subepithelial blistering diseases. Oral involvement is present in almost all patients, may represent the onset of the disease, and causes different degrees of pain, dysphagia, soreness, and bleeding. Treatment is based on systemic and/or oral corticoids, or other immunosuppressants. Occasionally, oral lesions can show a poor response to standard treatments. We present the case of a 61-year-old female patient with a painful extensive MMP oral ulcerative lesion recalcitrant to previous systemic azathioprine and local triamcinolone treatment, which was successfully treated in a novel way using PRGF infiltrations as adjuvant. After four weekly infiltrations, pain was reduced from 10 to 0 in a VAS and the lesion was completely healed. The patient continued with a low dose maintenance immunosuppressive treatment (prednisone 5 mg/day PO), and after 13 months of follow-up, there was no relapse of the lesion and no side effects. Although future research is necessary to confirm these observations, PRGF could be a useful adjuvant for the management of extensive mucous membrane pemphigoid oral lesions.

Cataract Surgery in Ocular Mucous Membrane Pemphigoid: A Risk, a Benefit or Both?

he aim of this study is to evaluate the effectiveness of phacoemulsification and Intraocular Lens (IOL) implantation in OcMMP patients. Data from 15 eyes of 10 patients affected by OcMMP that underwent phaco+IOL have been evaluated. Each patient was examined a week before surgery and at day 1, day 3, day 7 and 30 days after surgery

Topical Application of Minocycline Hydrochloride and Systemic Nicotinamide and Traditional Chinese Medicine for Benign Mucous Membrane Pemphigoid: A Case Report

A history of recurrent benign mucous membrane pemphigoid episodes had plagued patients. Major treatments include immunosuppressant or systemic glucocorticoid drugs, but all of them have side effects. Therefore, we tried to find a way to minimize side effects by using traditional Chinese medicine, and speeding up the healing process.