Levamisole-Adulterated Cocaine-Induced Mucous Membrane Pemphigoid: Case Reports and Literature Review.

PURPOSE: The aim of this study was to report 2 cases of levamisole-adulterated cocaine-induced mucous membrane pemphigoid. METHODS: This study is a review of case reports and literature. RESULTS: Two patients presented with bilateral severe purulent conjunctivitis, corneal ulceration, and rapidly progressive forniceal shortening. Both patients were active cocaine users. A complete blood analysis showed a positive antineutrophil cytoplasmic antibody immunofluorescence with a mixed perinuclear antineutrophil cytoplasmic antibody and cytoplasmic-staining antineutrophil cytoplasmic antibody pattern. Direct immunofluorescence examination of conjunctival tissue showed linear deposition of component 3 and immunoglobulins at the basal membrane. A diagnosis of levamisole-adulterated cocaine-induced mucous membrane pemphigoid was made. In case 1, this suspicion was confirmed by investigating remnants of cocaine on the patient's debit card using mass spectrometry, which contained traces of levamisole. In both cases, aggressive immunosuppressive therapy combining systemic corticosteroids and rituximab was able to control the disease. However, by the time these therapies were initiated, significant corneal injury had occurred requiring corneal grafts in both patients. CONCLUSIONS: Given the rising abuse of cocaine, it is important that ophthalmologists are made aware of its association with severe atypical cicatricial conjunctivitis. To the best of our knowledge, we present the first case proving the causal relationship between levamisole and ocular cicatricial pemphigoid.

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.

A novel case of ocular cicatricial pemphigoid induced by levamisole-adulterated cocaine.

AIM: To report a case of ocular cicatricial pemphigoid caused by levamisole-adulterated cocaine. METHODS: Case report. RESULTS: A 54-year-old woman with multi-systemic levamisole-induced vasculitis which triggered bilateral cicatrizing conjunctivitis refractory to conventional immunosuppressants due to continued cocaine misuse. CONCLUSION: Levamisole-induced vasculitis is a significant public health issue due to its popularity as an adulterant to cocaine. Our report suggests that levamisole caused vasculitis and ocular cicatricial pemphigoid in this case. Ocular manifestation of this syndrome is rare.

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.

[Pseudopemphigoid Induced by Topical Glaucoma Medications]. / Pseudopemphigoid bei topischer Glaukomtherapie.

Pseudopemphigoid is a chronic disease that causes progressive conjunctival scarring, up to symplepharon formation. Phenotypically, it cannot be distinguished from true mucous membrane pemphigoid with ocular involvement. Possible triggers are ocular surface disorders and/or their therapy. About 50% of all affected patients are glaucoma patients treated with topical antiglaucomatous therapy. Lack of signs of systemic disease, unilateral findings and/or a positive history of glaucoma may be indicative of a pseudopemphigoid. In this review, the two entities will be compared and the diagnostic as well as the therapeutic approach for suspected pseudopemphigoid under topical glaucoma therapy will be presented.

Gliptin Accountability in Mucous Membrane Pemphigoid Induction in 24 Out of 313 Patients.

Mucous membrane pemphigoids (MMPs) and bullous pemphigoid (BP) are autoimmune bullous diseases that share physiopathological features: both can result from autoantibodies directed against BP180 or BP230 antigens. An association has been reported between BP and intake of gliptins, which are dipeptidyl peptidase-IV inhibitors used to treat type 2 diabetes mellitus. Clinical and immunological differences have been reported between gliptin-induced BPs and classical BPs: mucosal involvement, non-inflammatory lesions, and target BP180 epitopes other than the NC16A domain. Those findings accorded gliptins extrinsic accountability in triggering MMP onset. Therefore, we examined gliptin intrinsic accountability in a cohort of 313 MMP patients. To do so, we (1) identified MMP patients with gliptin-treated (challenge) diabetes; (2) selected those whose interval between starting gliptin and MMP onset was suggestive or compatible with gliptin-induced MMP; (3) compared the follow-ups of patients who did not stop (no dechallenge), stopped (dechallenge) or repeated gliptin intake (rechallenge); (4) compared the clinical and immunological characteristics of suggestive-or-compatible-challenge patients to 121 never-gliptin-treated MMP patients serving as controls; and (5) individually scored gliptin accountability as the trigger of each patient's MMP using the World Health Organization-Uppsala Monitoring Center, Naranjo- and Begaud-scoring systems. 17 out of 24 gliptin-treated diabetic MMP patients had suggestive (≤12 weeks) or compatible challenges. Complete remission at 1 year of follow-up was more frequent in the 11 dechallenged patients. One rechallenged patient's MMP relapsed. These 17 gliptin-treated diabetic MMP patients differed significantly from the MMP controls by more cutaneous, less buccal, and less severe involvements and no direct immunofluorescence IgA labeling of the basement membrane zone. Multiple autoantibody-target antigens/epitopes (BP180-NC16A, BP180 mid- and C-terminal parts, integrin α6ß4) could be detected, but not laminin 332. Last, among the 24 gliptin-treated diabetic MMP patients, five had high (I4-I3), 12 had low (I2-I1) and 7 had I0 Begaud intrinsic accountability scores. These results strongly suggest that gliptins are probably responsible for some MMPs. Consequently, gliptins should immediately be discontinued for patients with a positive accountability score. Moreover, pharmacovigilance centers should be notified of these events.

Anti-laminin-332 mucous membrane pemphigoid developing after a diphtheria tetanus vaccination.

IMPORTANCE: Bullous pemphigoid (BP) has been previously described to develop after vaccination in 26 patients. Immunoblotting or enzyme-linked immunosorbent assays (ELISAs), which were performed for 7 of these patients, have always shown circulating autoantibodies against BP180 and/or BP230 antigens. A case of anti-laminin-332 mucous membrane pemphigoid (MMP) that developed shortly after a diphtheria tetanus vaccination is described, with a review of the literature on postvaccination BP. OBSERVATIONS: A 29-year-old man developed an acute eruption of oral and cutaneous blisters and erosions 2 days after receiving a diphtheria tetanus vaccination. The histopathological, immunohistochemical, immunofluorescent, ELISA, and immunoblotting assay results were compatible with anti-laminin-332 MMP. The serum autoantibodies reacted with the α3 and ß3 subunits of laminin-332. The disease was controlled by administering a combination of glucocorticosteroids and dapsone. CONCLUSIONS AND RELEVANCE: The development of acute MMP shortly after a diphtheria tetanus vaccination may have been serendipitous, a result of a nonspecific bystander activation of the immune system, or due to structural mimicry between domains of the toxoid molecule and a subunit of laminin-332.

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.

Corneal and conjunctival toxicity from hydrogen peroxide: a patient with chronic self-induced injury.

PURPOSE: To report a patient with severe corneal and conjunctival toxicity from long-term, habitual use of hydrogen peroxide as an eye wash. DESIGN: Observational case report. INTERVENTION AND TESTING: Serial examinations of the cornea, conjunctiva, and ocular adnexa were done. Penetrating keratoplasty with amniotic membrane transplantation was performed. MAIN OUTCOME MEASURES: Ocular inflammation, pain, and visual acuity outcome. RESULTS: Bilateral corneal and conjunctival inflammation and scarring mimicking ocular-cicatricial pemphigoid were noted. Formation of a descemetocele after starting treatment with low-dose topical steroids required emergent penetrating keratoplasty with amniotic membrane transplantation. CONCLUSIONS: This is the first reported case of ocular surface toxicity in a patient after deliberate chronic use of high-dose hydrogen peroxide. It highlights the value of obtaining a thorough medical and social history and the importance of direct questioning about the use of any medications or agents on the eyes before making a diagnosis or initiating therapy.

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.

[Mucocutaneous bullous pemphigoid induced by valsartan. A clinical case]. / Pemfigoide bolloso (bp) cutaneo-mucoso indotto da valsartan. Un caso clinico.

In the presence of immune-mediated vesiculo-bullous diseases, the oral pathologist should focus his attention not only on the diagnosis and treatment of the case, but should particularly investigate the state of genetic predisposition in relation to the HLA haplotype structure and look for the possible trigger factors for the disease. The detection of the trigger may guarantee a faster cure with a minimum therapeutic contribution. In the search for triggering factors, the drugs that are traditionally incriminated such as ACE inhibitors, Fans, antibiotics (penicillin and penicillamine), substances with -SH groups, tranquillisers, are not always involved in inducing vesiculo-bullous diseases. Substances considered innocuous are often to blame. We present a case of mucous-cutaneous bullous pemphigoid induced by an anti-hypertensive of the sartan group, valsartan.

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.