Radiation-Induced Laryngeal Mucous Membrane Pemphigoid.

OBJECTIVES: Bullous pemphigoid has previously been linked to radiotherapy, but here we report the first case of MMP suspected to be a consequence of RT. METHODS: The patient described is an 85-year-old male who underwent RT to treat squamous cell carcinoma of the palatine tonsil. Shortly after therapy, the patient developed blisters with worsening dyspnea and dysphonia. RESULTS: This patient was successfully treated with a combination of oral immunosuppressants and surgical intervention. CONCLUSION: This incident underscores that not all episodes of mucosal ulceration following radiation are a result of mucositis and MMP should be considered in the differential. LEVEL OF EVIDENCE: Level 4.

The role of Dipeptidyl Peptidase-4 in cutaneous disease.

Dipeptidyl peptidase-4 (DPP4) is a multifunctional, transmembrane glycoprotein present on the cell surface of various tissues. It is present in multiple molecular forms including cell surface and soluble. The role of DPP4 and its inhibition in cutaneous dermatoses have been a recent point of investigation. DPP4 exerts a notable influence on T-cell biology, the induction of skin-specific lymphocytes, and the homeostasis between regulatory and effector T cells. Moreover, DPP4 interacts with a broad range of molecules, including adenosine deaminase, caveolin-1, CXCR4 receptor, M6P/insulin-like growth factor II-receptor and fibroblast activation protein-α, triggering downstream effects that modulate the immune response, cell adhesion and chemokine activity. DPP4 expression on melanocytes, keratinocytes and fibroblasts further alters cell function and, thus, has crucial implications in cutaneous pathology. As a result, DPP4 plays a significant role in bullous pemphigoid, T helper type 1-like reactions, cutaneous lymphoma, melanoma, wound healing and fibrotic disorders. This review illustrates the multifactorial role of DPP4 expression, regulation, and inhibition in cutaneous diseases.

Abuse of vasoconstrictive eyedrops mimicking an ocular pemphigoid.

PURPOSE: To describe conjunctival histopathologic alterations induced by excessive chronic astringent use. METHODS: Report of a case with clinical picture, epicutane test results, histologic workup of conjunctival biopsy using conventional staining, and immunohistochemical markers. RESULTS: A 45-year-old man using a phenylephrine preparation hourly for years presented with grotesque eye redness, fornix shortening, and scarring of puncta lacrimalia. Direct and indirect immunofluorescence were negative for ocular pemphigoid. Histology revealed signs of chronic inflammation and neovascularization in the conjunctiva. Symptoms resolved after cessation of therapy. CONCLUSIONS: Chronic abuse of decongestant eyedrops can produce a clinical picture resembling an ocular pemphigoid. Histology suggests that late onset immunoreaction and chronic vasoconstriction cause chronic inflammation and neovascularization, respectively.

Methotrexate therapy for ocular cicatricial pemphigoid.

PURPOSE: To report the use of methotrexate therapy as first-line systemic therapy in the treatment of ocular-cicatricial pemphigoid and drug-induced ocular-cicatricial pemphigoid. DESIGN: Retrospective, noncomparative, interventional case series. PARTICIPANTS: Twelve patients with ocular-cicatricial pemphigoid and 5 patients with drug-induced ocular-cicatricial pemphigoid treated with low-dose oral methotrexate as the sole systemic agent. In 14 of the 17 patients, methotrexate was the first systemic agent used. METHODS: Clinical data abstracted from patient medical records. MAIN OUTCOME MEASURES: Visual acuity, conjunctival inflammation, progression of cicatrization, and treatment-related side effects. RESULTS: After a mean follow-up duration of 30.2 months (range, 6-78 months), complete control or suppression, or both, of conjunctival inflammation was achieved in 89% of eyes with ocular-cicatricial pemphigoid and in 100% of eyes with drug-induced ocular-cicatricial pemphigoid using methotrexate monotherapy as the first-line systemic agent. Progression of conjunctival cicatrization was prevented in 72% of eyes with ocular-cicatricial pemphigoid and 90% of eyes with drug-induced ocular-cicatricial pemphigoid. Visual acuity was maintained or improved in 85% of total eyes treated with methotrexate monotherapy, and a final visual acuity of 6/18 or better was achieved in 74% of the eyes. Methotrexate therapy was well tolerated, with 92% of patients maintained on continued treatment experiencing no side effects. The most common side effects were gastrointestinal (50%), and most (78%) were reversible on dose reduction. In 4 of 17 cases, methotrexate was ceased as a result of possible treatment-related side effects. CONCLUSIONS: Low-dose oral methotrexate monotherapy is both highly efficacious and well tolerated as the first-line systemic agent in the treatment of ocular-cicatricial pemphigoid and drug-induced ocular-cicatricial pemphigoid.

Amniotic membrane grafts, "fresh" or frozen? A clinical and in vitro comparison.

BACKGROUND/AIMS: The use of "fresh" (hypothermically stored) and frozen amniotic membrane (AM) was compared in a patient with cicatricial pemphigoid with stem cell failure. The viability of both "fresh" and frozen AM epithelial cells was assessed after storage. METHODS: AM was stored at either +4 degrees C ("fresh") or at -80 degrees C (frozen). A "fresh" graft was applied to the cornea following superficial keratectomy. Subsequently, a further frozen graft was applied to the same eye. Viability of the stored AM epithelium was assessed by investigating membrane integrity and mitochondrial activity. RESULTS: In both cases the cornea re-epithelialised and visual acuity improved. Improvement, however, was not sustained. CONCLUSION: Although both procedures led to an improvement in visual acuity, "fresh" tissue performed no better than frozen in promoting re-epithelialisation. The authors suggest that logistical, safety, and cost considerations outweigh any benefits of using "fresh" as opposed to frozen graft material.

Conjunctival changes associated with glaucoma therapy: implications for the external disease consultant and the treatment of glaucoma.

PURPOSE: Enhance recognition by the external disease specialist of the conjunctival changes associated with glaucoma therapy and the reported association with glaucoma filtration surgery. METHODS: Literature search with emphasis on the cellular and subcellular changes induced by antiglaucoma medications, the definition and diagnosis of drug-induced cicatricial conjunctivitis (DICC), and the implications for future glaucoma therapy or surgery. RESULTS: Significant conjunctival and subconjunctival changes occur associated with the use of antiglaucoma medications that affect the success of glaucoma filtration surgery. The extreme form of change is the DICC, which is clinically and pathologically identical to ocular cicatricial pemphigoid. The autoantigen in the basement membrane probably differs in these two disease processes. CONCLUSIONS: There is a movement toward an earlier approach to glaucoma filtration surgery, in large part based on the literature reviewed here. The external disease specialist needs to be cognizant of these conjunctival changes to best consult on patients receiving antiglaucoma medications.

Drug-induced ocular cicatricial pemphigoid: a series of clinico-pathological reports.

Ocular cicatricial pemphigoid is a slowly progressive disease of mucous membranes and skin of unknown but presumed autoimmune aetiology. We describe eight cases of presumed drug-induced cicatrising conjunctival changes simulating ocular cicatricial pemphigoid, following the chronic use of topical glaucoma medication. In three of four patients who underwent conjunctival biopsy of the inferior fornix, this revealed histopathological changes similar to ocular cicatricial pemphigoid.

[Ocular pseudopemphigoid after topical drug administration]. / Okuläres Pseudopemphigoid nach topischer Medikamentenapplikation.

BACKGROUND Since it's first description in 1974 by Kristensen and Norn numerous substances have been reported as potential causes for drug-induced pseudopemphigoid. The signs and symptoms are as severe as with ocular cicatricial pemphigoid. It seems to be most important for the visual outcome for how long the inducing drug was applied and how soon it has been stopped after the first signs. PATIENTS Six female patients were investigated. All six patients presented the clinical picture of a cicatricial pemphigoid but this was not confirmed by immunostaining. The average age of these patients was 72.5 +/- 8.1 years. In 5 of these patients topical antiglaucomatous drugs are thought to be the inducing factor. The average interval from the start of medication until the appearance of the first symptoms was 14.8 +/- 5.3 years. CONCLUSIONS. The drug-induced ocular pseudopemphigoid is a serious but rare consequence of long-term topical medication. This potential risk should be carefully balanced against the benefit of long-term topical therapy.

Drug-induced cicatricial pemphigoid affecting the conjunctiva. Light and electron microscopic features.

Cicatricial pemphigoid (CP) is a chronic inflammatory disease which can affect the conjunctiva. It is a slowly progressive disorder of unknown but presumed autoimmune etiology. Pseudopemphigoid, or CP associated with ocular drug administration, has also been described. These cases, which appear clinically indistinguishable from unilateral idiopathic CP affecting the conjunctiva, have been related to the use of echothiophate iodide, pilocarpine, idoxuridine, and epinephrine. We report the histopathologic and ultrastructural characteristics of 22 biopsies from ten patients with iatrogenic CP following the use of various ocular drugs. All patients presented with clinically obvious, active CP affecting the conjunctiva. Light microscopy and electron microscopy revealed findings identical to those previously reported for idiopathic CP of the conjunctiva: squamous metaplasia, increased numbers of desmosomes, basal lamina modifications suggestive of damage and attempted repair, subepithelial inflammatory cell infiltration, and diminished intravascular space within the stroma. These patients responded to immunosuppressive therapy. The authors wonder if it is possible that these patients were destined to develop CP, but that with topical ocular drug use, a more rapid emergence of the chronic cicatrizing feature of CP developed.

Idoxuridine-induced conjunctival cicatrization.

Four patients had idoxuridine-induced conjunctival cicatrization similar to ocular cicatricial pemphigoid develop, but in the treated eye only. Three of the four patients had chronic, recurrent herpes simplex epithelial and stromal keratitis. The fourth patient had Sjögren's syndrome. All received idoxuridine (0.1% drops and/or 0.5% ointment) and topical corticosteroids from one to 3 1/2 years. Substantial morbidity resulted that included visual loss, stromal ulceration, corneal scarring, and keratinization. Conjunctival biopsy specimens showed cicatrization with a mixed inflammatory cell reaction and absence of goblet cells. Results of direct immunofluorescent microscopy of the conjunctiva were either negative or nonspecific for autoantibody. No circulating autoantibody was detected in any of the four patients.