Contact allergens responsible for eyelid dermatitis in adults.

Allergic contact dermatitis has been established as the most frequent cause of eyelid dermatitis, but it is often misdiagnosed. The purpose of this study was to evaluate the characteristics of patients with eyelid dermatitis who were referred for patch testing. The patients were divided into three subgroups in this retrospective study: patients with only eyelid involvement, patients with involvement of eyelids and other areas, and patients without eyelid involvement. Data was collected on diagnoses, medical history, personal care products and make-up use, occupational dermatitis, and positive allergens. An independent t-test, one-way ANOVA, and chi-squared test were used to analyze the data. A total of 427 patients who referred for patch tests were included in the study. Of these, 139 patients had eyelid dermatitis. Allergic contact dermatitis (ACD) was the most common diagnosis in all three groups referred for patch tests. Use of shaving cream and hair conditioner was significantly higher in patients with only eyelid involvement and nickel sulfate was the most common allergen among them. Patch testing is the gold standard tool in the evaluation of eyelid contact dermatitis, and it is a necessity in the treatment of eyelid dermatitis, for the accurate identification of responsible allergens.

Neutrophils cause obstruction of eyelid sebaceous glands in inflammatory eye disease in mice.

Meibomian glands (MGs) are sebaceous glands of the eyelid margin that secrete lipids needed to avert tear evaporation and to help maintain ocular surface homeostasis. Obstruction of MGs or other forms of MG dysfunction can promote chronic diseases of the ocular surface. Although chronic eyelid inflammation, such as allergic eye disease, is an associated risk factor for obstructive MG dysfunction, it is not clear whether inflammatory processes contribute to the pathophysiology of MG obstruction. We show that polymorphonuclear neutrophils (PMNs) promoted MG obstruction in a chronic inflammatory model of allergic eye disease in mice. Analysis of leukocytes in tears of patients with MG dysfunction showed an increase in PMN numbers compared to healthy subjects. Moreover, PMN numbers in tears positively correlated with clinical severity of MG dysfunction. Our findings point to a role for PMNs in the pathogenesis and progression of MG dysfunction.

Immunopathology and histopathology of conjunctival biopsies in patients with presumed idiopathic punctal stenosis.

BACKGROUND/AIMS: Numerous processes have been implicated as causes of punctal stenosis. Recent studies have highlighted inflammation in punctoplasty specimens in patients with punctal stenosis. Conjunctival biopsy has been suggested as a means to determine underlying aetiologies, although little is known regarding what conjunctival pathologies are associated with punctal stenosis. Our objective is to examine the pathological and immunological findings in conjunctival biopsy specimens in patients with presumed idiopathic punctal stenosis. METHODS: A retrospective chart review was performed at a single institution over a 5 year period of patients with presumed idiopathic punctal stenosis who underwent conjunctival biopsy for histopathological and/or direct immunofluorescence (DIF) examination. Patients with known aetiologies of punctal stenosis were excluded. RESULTS: 23 patients met inclusion criteria. Conjunctival biopsies (n=36) from all 23 patients underwent histological examination. 35 specimens (97.2%) showed lymphocytic infiltrates. Two patients (8.7%) had findings suggestive of sarcoidosis. Conjunctival biopsies from 18 of the 23 patients were also evaluated by DIF. Nine patients (50.0%) had fibrinogen characteristics suggestive of lichen planus. There were no complications related to the conjunctival biopsy procedures. CONCLUSIONS: Conjunctiva appears to be an excellent proxy in evaluating patients with presumed idiopathic punctal stenosis. The biopsy is safe and provides ample tissue. Clinically, abnormal tissue should be targeted, if available. 11 of the 23 patients in this study demonstrated findings consistent with underlying immunological disorders, suggesting that conjunctival biopsy may play a role in identifying underlying aetiologies of punctal stenosis. Knowledge of these underlying conditions impacted treatments for several patients.

Molluscum contagiosum of the eyelid: case report in a man receiving methotrexate and literature review of molluscum contagiosum in patients who are immunosuppressed secondary to methotrexate or HIV infection.

BACKGROUND: Molluscum contagiosum is a benign viral infection of the skin. Lesions typically present as dome-shaped, flesh-colored, umbilicated papules that range in size from 1 to 5 millimeters in diameter. They are usually asymptomatic, but can become tender or pruritic. Children and immunocompromised adults, including individuals being treated with immunosuppressive drugs, are most susceptible to infection. Single or multiple lesions most commonly appear on the extremities, face, genitals, and trunk. However, albeit rarely, molluscum contagiosum may also develop at other sites, including the eyelids. PURPOSE: We describe the clinical and pathologic findings of a man who developed molluscum contagiosum of the eyelid while receiving methotrexate. We also review the characteristics of other patients with molluscum contagiosum acquired either during treatment with methotrexate or associated with human immunodeficiency virus (HIV) infection and summarize the unusual sites of presentation for the viral lesions in these individuals. MATERIALS AND METHODS: The features of a man receiving methotrexate who developed molluscum contagiosum of the eyelid are presented. Using PubMed, the following terms were searched and relevant citations assessed: adalimumab, contagiosum, Enbrel, etanercept, Humira, infliximab, methotrexate, molluscum, Remicade, TNF alpha, and tumor necrosis factor alpha. In addition, the literature on methotrexate treatment and molluscum contagiosum is reviewed. RESULTS:  Several small papules were observed on the eyelid of a 24-year-old man who had been receiving methotrexate and adalimumab (Humira) for the treatment of Crohn disease. The lesions were removed by shave biopsy. Microscopic examination revealed epidermal hyperplasia composed of keratinocytes filled with large eosinophilic intracytoplasmic inclusions. Based on correlation of the clinical presentation and histopathologic findings, a diagnosis of molluscum contagiosum was established. The patient applied mupirocin 2% ointment to the biopsy sites, which subsequently healed without complication or recurrence. CONCLUSION: Molluscum contagiosum is a benign viral papular eruption that frequently affects children and immunocompromised adults. Patients treated with immunosuppressive agents, such as methotrexate, have a heightened risk of developing molluscum contagiosum lesions. It remains to be determined whether adjunct therapy with a tumor necrosis factor alpha inhibitor increasesthe risk of this viral infection. Diagnosis can usually be established by clinical presentation, although a biopsy is sometimesrequired to exclude other conditions. Molluscum contagiosum is generally self-limiting and often resolves spontaneously within18 months. However, topical (cantharidin) or locally destructive (curettage, cryotherapy, and/or laser) therapy may be indic tedfor patients who are concerned about persistent lesions and for children who are particularly susceptible to autoinoculation.

Immunologic Mediators in Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are a spectrum of T-cell mediated immune disorders. While the contributory mechanisms leading to the apoptosis of epidermal cells in SJS/TEN remain unproven, the keratinocyte apoptosis seen in SJS/TEN is thought to occur through the T-cell mediated Fas-Fas ligand (FasL), perforin/granzyme B, and other immune mediators. Most recently, emphasis has been placed on the granulysin pathway as being the primary mediator of apoptosis and widespread epidermal necrosis in SJS/TEN. This article aims to review the proposed mechanisms by which these pathways work and the immunomodulatory therapies that have been developed in an attempt to target them.

Eyelid edema as a predictive factor for sensitization to Pru p 7 in peach allergy.

The clinical and laboratory factors related to Pru p 7 sensitization in peach allergy, compared with those associated with sensitization to Pru p 1, which is related to pollen-food allergy syndrome (PFAS), have still not been clarified. The aim of the present study was to identify the clinical and laboratory features associated with sensitization to Pru p 7. Fifty patients (male : female, 14:36; mean age, 31.8 years) with peach allergy were enrolled in this study. Specific immunoglobulin E (sIgE) against the purified nPru p 7 was measured by enzyme-linked immunoassay, whereas using ImmunoCAP, sIgE levels against peach, rPru p 1, rPru p 3 and rPru p 4 were measured. Correlations between the clinical characteristics of peach allergy and sensitization to the allergens were statistically analyzed. In 50 patients with peach allergy, 13 and 33 patients were sensitized with nPru p 7 and rPru p 1, respectively. Laryngeal tightness, conjunctival injection, facial edema, eyelid edema and urticaria were significantly associated with Pru p 7 sensitization. In contrast, oropharyngeal symptoms were strongly related to Pru p 1 sensitization but were significantly less common in the Pru p 7-positive group. Co-sensitization to the representative pollens related to PFAS, such as alder pollens, was significantly related to Pru p 1 sensitization, but not Pru p 7 sensitization. Along with the absence of co-sensitization to pollens related to PFAS, facial edema and especially eyelid edema after the ingestion of peaches could be a predictive factor for sensitization to Pru p 7.

Adult Onset Asthma and Periocular Xanthogranuloma (AAPOX), a Rare Entity With a Strong Link to IgG4-Related Disease: An Observational Case Report Study.

Adult onset asthma and periocular xanthogranuloma (AAPOX) is a rare non-Langerhans histiocytosis characterized histopathologically by a periocular infiltration of foamy histiocytes and Touton giant cells. Benign hyperplasia with plasma cell infiltration is classically described in eyelids or lymph nodes of AAPOX patients. It is also a characteristic feature of IgG4-related disease (IgG4-RD), a new entity defined by an IgG4-bearing plasma cell infiltration of organs.To determine if AAPOX syndrome shares clinical, biological, and histopathological characteristics with IgG4-RD, we used the comprehensive clinical diagnostic criteria for IgG4-RD in a retrospective case series of three consecutive patients with histologically-proven AAPOX. Patients who were diagnosed with AAPOX at a French academic referral center for orbital inflammation between November 1996 and March 2013 were enrolled. Biopsies from ocular adnexa or other organs were systematically reexamined. For each patient, clinical and serological data, radiologic findings, and treatment were retrospectively analyzed.Two AAPOX patients fulfilled all of the diagnostic criteria for a definite IgG4-RD. One patient who lacked the serological criteria fulfilled the criteria of a probable IgG4-RD.These 3 cases of AAPOX patients fulfilled the IgG4-RD comprehensive clinical diagnostic criteria. To our knowledge, this is the first observational case report study to clearly show a strong relationship between IgG4-RD and AAPOX syndrome.

Inflammatory pseudotumor of eyelid: a probable IgG4-related sclerosing disease clinically mimicking eyelid pilomatrixoma.

BACKGROUND: Ocular adnexal IgG4-related sclerosing disease (IgG4-SD) has been categorized as a novel disease entity. It is characterized by stromal sclerosis and an infiltration of mass-forming lymphoplasmic cells containing many IgG4-positive plasma cells. Although ocular adnexal tissue involvement has been increasingly reported, a focal nodular sub-brow mass is not typical in an IgG4-SD presentation. We report a rare case of probable ocular adnexal IgG4-SD that clinically mimicked eyelid pilomatrixoma. CASE PRESENTATION: A 42-year-old woman presented with a nodular mass in her left sub-brow area. The initial clinical impression of her lesion was eyelid pilomatrixoma. However, the final pathologic diagnosis was IgG4-SD, but extranodal marginal zone B-cell lymphoma could not be excluded. The patient underwent testing to determine tumor malignancy and systemic IgG4-SD involvement. Laboratory testing showed normal IgG and IgG4 serum levels and imaging revealed no remarkable findings. Oral prednisolone was administered and slowly tapered to manage the possible remnant lesion and to prevent disease recurrence. Two years after initiating therapy, there was no evidence of relapse. The patient is under close surveillance for signs of recurrence, systemic involvement, and potential malignant transformation. CONCLUSIONS: We found an unusual case of probable ocular adnexal IgG4-SD, which presented as a unilateral restricted mass involving the sub-brow area. Although the mass was surgically removed, systemic steroid treatment and long-term surveillance were initiated due to the possibility of recurrence, the potential association with systemic disease, and the potential development of extranodal mucosa-associated lymphoid tissue (MALT) lymphoma.

Ocular adnexal IgG4-related disease: clinical features, outcome, and factors associated with response to systemic steroids.

PURPOSE: The aim of this study was to investigate clinical characteristics, outcome, and factors associated with response to systemic administration of steroids in patients with ocular adnexal immunoglobulin G4 (IgG4)-related disease. METHODS: This was a retrospective evaluation of 11 patients with histopathologically verified ocular adnexal IgG4-related diseases at a medical center in Taiwan between January 2006 and December 2012. Clinical features and outcome, including serial change of serum IgG4 and clinical factors related to response to steroids systemically were evaluated. RESULTS: Seven men and four women, mean age 54.5 years and mean follow-up of 33.5 months, were evaluated. Elevated serum IgG4 levels (>135 mg/dl) were observed in ten patients (91%). Lacrimal gland involvement was noted in eight (72.7%), followed by orbit, extraocular muscles, and eyelids. Seven patients (63.6%) had bilateral ocular lesions and eight (72.7%) had extraorbital involvement. Eight of ten patients who underwent systemic steroid treatment responded well in the early phase. Recurrence developed in five patients (45%), requiring repeat steroid therapy and adjunctive treatment. Median serum levels of IgG4 reduced from 540 to 101 mg/dl in ten patients after systemic corticosteroid administration. Patients with lower serum IgG4 and IgG4:IgG ratio at diagnosis were associated with poor response (p = 0.037). CONCLUSIONS: Ocular adnexal IgG4-related disease predominantly involved the lacrimal glands bilaterally and was usually associated with high serum IgG4 levels and multiple organ involvement. Most patients responded well to steroid therapy, which was accompanied by a marked decrease in serum IgG4.

Melkersson-Rosenthal syndrome with isolated unilateral eyelid edema: an immunopathologic study.

Lymphedema is caused by defective drainage of the lymphatic system. In Melkersson-Rosenthal syndrome, involvement is predominantly of the lumens with blockage of lymphatic channels by histiocytic-epithelioid cell clusters accompanied by dermal granulomas and lymphocytes. It is a localized, painless, nonitching, and nonpitting form of lymphedema. Besides the eyelids, the disease can cause lip edema, facial palsy, and/or fissured tongue. It is rare and has received little attention in the ophthalmic literature, either in its complete triadic form, or more frequently, in its monosymptomatic forms. Pathogenesis is not well understood, and there is no effective therapy. The authors describe a case of Melkesson-Rosenthal syndrome in a 45-year-old Hispanic man with isolated unilateral upper eyelid edema. Histopathological and immunohistochemical evaluations of an eyelid biopsy specimen revealed intravascular and extravascular clusters of histiocytic-epithelioid cells that were CD68/163-positive. Variable numbers of mostly T-lymphocytes were found in the epidermis, dermis, and orbicularis muscle and by virtue of the associated granulomas established the diagnosis of Melkersson-Rosenthal syndrome. CD4 helper and CD8 suppressor T-lymphocytes were equally represented. CD20 B-lymphocytes were exceedingly sparse. Conspicuous CD1a-positive Langerhans' cells were present in the epidermis, sometimes formed subepithelial loose aggregates and were also incorporated in the granulomas. The differential diagnosis includes the far more common condition of acne rosacea. Management of Melkersson-Rosenthal syndrome, and of angioedema in general, is reviewed.