Pemphigus vulgaris (PV) is a chronic autoimmune blistering disorder characterized by the loss of intraepithelial adhesion affecting the skin and mucous membranes, predominantly affects females in their fifth and sixth decades of life. Due to its rare occurrence in children and adolescents, there is often a delay in diagnosis and treatment in this age group. PV should always be considered in the differential diagnosis of oral ulcerative and vesiculobullous lesions in both children and adolescents.

Vesiculobullous disorders are a group of autoimmune diseases manifesting as chronic ulcers in the oral cavity. Ocular involvement may accompany oral ulcers and cause various problems for patients. This review summarizes the data regarding ocular involvement in patients with oral vesiculobullous.

Web of Science, Scopus, PubMed/MEDLINE, and Embase electronic databases were searched according to related keywords. Finally, 58 articles were included, all of which were case reports or series. Characteristics such as the age and sex of patients, location and type of oral lesion, type of ophthalmic injury, the interval between oral and ocular lesion, and treatment of oral and ocular disorders were summarized in tables.

Eye involvement was 1.6 times more prevalent in women, and most patients were between 30 and 60 years old (67.4 %). Pemphigus vulgaris accounted for almost half of the cases (48.4 %), though lichen planus is more prevalent in the general population. The most frequently affected oral site was the buccal mucosa (17.5 %), and oral ulcers usually presented as erythema, erosion, or inflammation (22.7 %). Conjunctivitis was the most common type of eye involvement (18.4 %), and ophthalmic lesions regularly appeared 12-60 months after the development of oral lesions (30.1 %). Blindness was reported in only one case. Corticosteroids and immunosuppressives were the most frequent oral and ocular lesion therapies.

Considering the serious burdens of any ocular injury, monitoring the ocular health of patients with oral vesiculobullous diseases is highly recommended in high-risk cases, especially middle-aged women with oral pemphigus vulgaris.

Autoimmune bullous diseases with ocular involvement consist of a group of systemic entities that are characterized by formation of autoantibodies against the proteins of the epithelial basement membrane zone of the conjunctiva. Mostly, the elderly are affected by these diseases. The characteristic patterns of mucocutaneous involvement and the specific tissue components targeted by these autoantibodies are differentiating features of these diseases. Ocular pemphigus vulgaris exhibits intraepithelial activity, whereas the autoimmune activity in linear immunoglobulin A disease, mucous membrane pemphigoid, and epidermolysis bullosa acquisita occurs at a subepithelial location. Given the increased risk for blindness with delays in diagnosis and management, early detection of ocular manifestations in these diseases is vital. The precise diagnosis of these autoimmune blistering diseases, which is essential for proper treatment, is based on clinical, histological, and immunological evaluation. Management usually includes anti-inflammatory and immunosuppressive medications. Inappropriate treatment results in high morbidity and even potential mortality.

The TFOS DEWS II Pathophysiology Subcommittee reviewed the mechanisms involved in the initiation and perpetuation of dry eye disease. Its central mechanism is evaporative water loss leading to hyperosmolar tissue damage. Research in human disease and in animal models has shown that this, either directly or by inducing inflammation, causes a loss of both epithelial and goblet cells. The consequent decrease in surface wettability leads to early tear film breakup and amplifies hyperosmolarity via a Vicious Circle. Pain in dry eye is caused by tear hyperosmolarity, loss of lubrication, inflammatory mediators and neurosensory factors, while visual symptoms arise from tear and ocular surface irregularity. Increased friction targets damage to the lids and ocular surface, resulting in characteristic punctate epithelial keratitis, superior limbic keratoconjunctivitis, filamentary keratitis, lid parallel conjunctival folds, and lid wiper epitheliopathy. Hybrid dry eye disease, with features of both aqueous deficiency and increased evaporation, is common and efforts should be made to determine the relative contribution of each form to the total picture. To this end, practical methods are needed to measure tear evaporation in the clinic, and similarly, methods are needed to measure osmolarity at the tissue level across the ocular surface, to better determine the severity of dry eye. Areas for future research include the role of genetic mechanisms in non-Sjögren syndrome dry eye, the targeting of the terminal duct in meibomian gland disease and the influence of gaze dynamics and the closed eye state on tear stability and ocular surface inflammation.

Ocular/periocular involvement in pemphigus vulgaris (OPV) has rarely been reported. The objective of the present study was to investigate the pattern of OPV and define the prognostic value of its manifestation.

From 1985 to 2014, a total of 167 patients with pemphigus vulgaris (PV) were treated at four tertiary Spanish hospitals. In this retrospective study, we included all patients with OPV. Clinical data and information on associated symptoms were obtained from patients' medical records.

Only 24 (14.3 %) of all PV patients had ocular lesions. In most cases, -ocular involvement was preceded by PV lesions at various other sites (mean duration: 33.7 months). Ocular PV lesions occurred during flares of mucocutaneous pemphigus, and was never the only mucosal manifestation. The most common clinical signs were conjunctival hyperemia (87.5 %), erosions on the eyelids (41.6 %) as well as of the palpebral/bulbar conjunctiva (33.3 %) and at the medial epicanthus (20.8 %). The most relevant associated symptoms included local pain/stinging (71.4 %), irritation (47.6 %), photophobia (38.1 %), and epiphora (23.9 %). Ocular PV improved with systemic and adjuvant topical therapies. Only two patients experienced sequelae.

In patients with PV, ocular involvement is an exception. Ocular PV is associated with greater disease activity, and usually follows a benign course. Sites affected are the conjunctiva, the eyelids, or both.

To describe the clinical characteristics of ocular involvement in patients with pemphigus at an ophthalmological referral center.

A retrospective review was conducted on patients with the immunopathological diagnosis of pemphigus examined between 1 January 2000 and 1 April 2010. Uncorrected distance visual acuity (UDVA), best corrected distance visual acuity (BCVA), ocular symptoms, and ocular surface inflammatory and scarring changes were assessed.

A total of 15 patients were identified, with a mean age of 68.27 ± 14.35 years, and 80% (n=12) were female. Extraocular involvement was reported in one patient. All of the eyes showed cicatricial changes in the conjunctiva. In all, 6 eyes (20%) were classified as stage I; 12 eyes (40%) as stage II; 10 eyes (33%) as stage III; and 2 eyes (7%) as stage IV. A statistically significant association was found between BCVA and the severity of ocular involvement. The mean BCVA logMAR was 1.66 (20/914), with a range from logMAR 0 (20/20) to logMAR 4 (NLP). Other ocular diseases were found in 8 (53.3%), systemic diseases in 10 (66.7%), and the use of pemphigus-inducing drugs in 10 patients (66.7%).

The present report represents the largest series of ocular involvement in pemphigus confirmed by immunopathology. The clinical manifestations varied from conjunctival hyperemia to corneal scarring and perforation. There was a strong association between scarring changes and low BCVA. Ocular and systemic diseases as well as the use of pemphigus-inducing drugs may predispose to ocular cicatricial changes observed in this series.

Pemphigus vulgaris (PV) is an autoimmune blistering disease that affects mucous membranes and the skin. Most commonly, the disease begins in the oral cavity and spreads to other areas including the conjunctiva and eyelids. Ocular involvement is rare and likely underdiagnosed with a frequency that is underestimated. Ocular manifestations of systemic PV can imply severe disease and require a multidisciplinary approach.

A 43-year-old black female presented with a chief complaint of pain with a white stringy discharge in the left eye for 2 weeks. On questioning, her health history revealed a 20-year systemic history of PV. Assessment of the anterior segment revealed diffuse conjunctival hyperemia with an area of bulbar conjunctival erosion. Based on the constellation of history, signs, and symptoms, ocular PV was diagnosed precipitating treatment for the ocular lesions and referral to the dermatologist for control of the underlying systemic condition.

PV is an autoimmune disease of the pemphigus classification. It is characterized by the production of autoantibodies that attack intercellular substances. We review this unusual entity, its immunopathology, and treatment.

Ocular manifestations are a comorbidity of a group of chronic autoimmune blistering diseases that includes mucous membrane pemphigoid, linear immunoglobulin A disease, epidermolysis bullosa acquisita, and ocular pemphigus vulgaris. Various diagnostic measures differentiate between the diseases and allow for appropriate treatment including a specific selection of immunomodulatory medications. New treatment modalities offer alternatives that may minimize disease severity and residual tissue damage and may reduce treatment-related complications.

Pemphigus vulgaris is an autoimmune bullous disease characterized by blistering and erosions within skin and mucous membranes. Lesions appear most commonly on mucosal surfaces of the oral cavity. Ocular involvement in patients with PV has rarely been reported.

A 47-year-old male patient with a 2 month history of oral erosions and dysphagia developed severe conjunctivitis with periodical presence of purulent discharge, photophobia and burning sensations. The diagnosis of pemphigus vulgaris was confirmed by histopathology, direct immunofluorescence and detection of anti-desmogelin 3 antibodies in patients' serum. Treatment was introduced with prednisone at a dose of 80 mg per day (1 mg/kg) and cyclophosphamide at a dose of 100 mg daily (1.25 mg/kg). After 7 days of therapy a significant reduction of eye symptoms was observed and after 4 weeks of treatment full clinical remission was achieved.

The grounds for rare involvement of conjunctiva in pemphigus vulgaris is unclear. We hypothesize that inactivation of conjunctival desmoglein 3 may be compensated by other desmosomal proteins. Severe conjunctivitis may be the dominating clinical manifestation in pemphigus vulgaris. This implies a need of establishing distinct severity criteria and therapeutic standards for ocular pemphigus. In our patient rapid clinical response was achieved after introducing combined treatment with prednisone and oral cyclophosphamide.

The aim of our study consisted to measure the pharmacokinetic parameters of methylprednisolone administered in a continuous infusion of a paediatric parenteral nutrition mixture for 24h in the rabbit.

Fourteen rabbits were split into two groups and assigned a different administration vehicle (all-in-one or two-in-one nutrition mixture). We used USC PACK* pharmacokinetics software to compare the influence of the composition of the paediatric parenteral nutritional solutions on the values of the pharmacokinetic parameters of methylprednisolone.

Neither the steady-state plasma concentrations of methylprednisolone hemisuccinate nor the values of the pharmacokinetic parameters of methylprednisolone differed significantly when administered in two-in-one or all-in-one nutrition mixtures.

The composition of the nutritional medium had no discernable effect on the bioavailability of methylprednisolone. Neither the speed at which the steady-state plasma concentration was reached, nor the values of the pharmacokinetic parameters of methylprednisolone were significantly modified.

To report the occurrence of ocular involvement in the setting of pemphigus and discuss its relationship with disease activity and prognostic significance.

Retrospective case reports.

Five patients, aged 38 to 65 years, diagnosed with pemphigus according to clinical, histopathologic, and immunopathologic criteria (n = 4 pemphigus vulgaris; n = 1 superficial pemphigus) developed ocular symptoms and signs consistent with the disease, ranging from mild conjunctivitis to blisters and prominent erosions of the bulbar/palpebral conjunctiva or at the eyelid margin.

Ocular involvement in our series mostly followed skin disease or represented the stigmata of quiescent localized pemphigus. One of five patients had fatal outcome from myocardial infarction, whereas in the remaining cases significant improvement was achieved with oral prednisolone.

Ocular pemphigus is probably underdiagnosed and its frequency appears underestimated. It does not seem to correlate with disease severity, but may persist chronically after healing of cutaneous lesion.

The ocular manifestations of autoimmune bullous diseases are common and potentially sight-threatening. Major ophthalmic involvement is most commonly seen in mucous membrane pemphigoid (cicatricial pemphigoid), epidermolysis bullosa acquisita, linear IgA bullous disease, pemphigus vulgaris and paraneoplastic pemphigus. The main pathological process is related to autoimmune-induced conjunctival inflammation with consequent lid and corneal pathology, which may eventually result in permanent visual loss. Ocular involvement can be asymptomatic. Early detection is aided by careful attention to symptoms and signs of early ophthalmic disease. Ocular disease can be difficult to treat and management usually involves systemic therapy with immunomodulators to control inflammation and prevent progression to irreversible blindness, as well as surgical intervention in advanced disease. Recent advances in treatment, including methotrexate, mycophenolate mofetil, monoclonal antibodies and topical tacrolimus therapies, have led to promising results.

Ocular involvement in patients with pemphigus vulgaris (PV) has been rarely reported. We report ocular involvement in 11 patients with PV.

Medical records of 11 biopsy-proven patients with PV treated during the period between 1990 and 2003 were reviewed and clinical information was analyzed.

Mean age at onset of PV was 52.3 years (range, 30-80 years). Ocular disease was preceded by involvement of the skin, other mucosae, or both in all patients. Ocular involvement was limited to the conjunctivae, the eyelids, or both. PV did not affect the visual acuity of any of the patients. Suprabasal acantholysis was observed on routine histologic examination of the conjunctiva and skin of the eyelid. Direct immunofluorescence of perilesional eyelid skin demonstrated deposition of IgG on epithelial cell surface. Mean duration of follow up was 48.9 months (range, 4-100 months). Recurrence of ocular disease occurred in 3 patients; recurrence at nonocular mucosae occurred in 4 patients. No sequelae were observed during detailed follow-up. Ocular pemphigus improved with systemic therapy. The mean remission period was 32 months (range, 0-92 months).

Ocular involvement in PV is rare. Involvement is limited to the conjunctiva, the eyelids, or both. PV does not appear to affect visual acuity. Patients have full recovery without sequelae.

A woman aged 57 years had conjunctivitis of the right eye since February 2003. It had started with a pinhead-sized blister at the margin of the upper eyelid and was progressive in nature. Intense redness of the right eye, lacrimation, and severe pain confined to the right forehead were the major complaints. She had been under medical care ever since, without any tangible outcome. Its refractory nature impelled the ophthalmologist to seek dermatologic consultation, for apparently the diagnosis seemed to have eluded the consultant. Accordingly, she reported on March 2, 2004 for the opinion of severe incessant itching, profuse lacrimation, and pain that was confined only to the right eye and forehead. The very fact that she had reported with continuous rubbing of the right eye re-enforced the suspicion of the episode being an exclusive expression of pemphigus vulgaris of the eye that probably was the reason for ineffectiveness of the drugs given thus far to her. Examination of the right eye was marked by intense inflammation of the palpebral and bulbar conjunctiva, apparent in the form of severe redness (Figure 1). The conjunctiva was studded with several scattered minute erosions. Corneal opacity and cataract were its accompaniment, whereas the left eye was normal. Mucous membrane of the oral cavity was thoroughly scanned for blister and/or erosions but was normal. The rest of the skin surface was also unaffected. Nikolsky's sign was elicited by asking the patient to rub the eye. In fact, this was responsible for periodic recurrence of the episode. Tzanck test was performed by preparing, fixing, and Giemsa staining the smear from one of the erosions over the conjunctiva. The stained slides were examined under oil-immersion, which revealed plentiful acantholytic cells characterized by large nucleus containing nucleoli and occupying almost the entire eosinophilic cytoplasm and basophilic cell wall. The two biopsies from the conjunctiva were also taken with the help of a 3-mm punch. One of the biopsies was subjected to serial sections. The sections were stained with hematoxylin and eosin stain and examined by light microscopy. The presence of split/cleavage in the epidermis (intraepidermal) above the basal (suprabasal) was cardinal. The cleavage was filled with acantholytic cells of characteristic morphology (vide supra) (Figure 2). The other biopsy was subjected to direct immunofluorescence and was found complementary to the preceding microscopic pathology. Routine investigations comprising total and differential leukocyte count, liver and kidney function tests, chest skiagram, and electrocardiogram were normal. The preceding findings were fairly conducive to form the diagnosis of erosive conjunctivitis emanating from pemphigus vulgaris. Accordingly, pulse therapy (intermittent high-dose) containing 100 mg dexamethasone in 5% glucose daily by slow IV infusion on 3 consecutive days, along with 500 mg of cyclophosphamide on Day 1 only followed by continuous low-dose 50 mg cyclophosphamide, was administered. The patient has since recovered completely and is now under surveillance.