George N. Papaliodis

Stevens-Johnson syndrome and toxic epidermal necrolysis: A review of the literature

OBJECTIVE To perform a comprehensive review of Stevens-Johnson syndrome and toxic epidermal necrolysis. DATA SOURCES A MEDLINE search was performed for the years 1975 to 2003 using the keywords Stevens-Johnson syndrome and toxic epidermal necrolysis to identify relevant articles published in English in peer-reviewed journals. STUDY SELECTION All clinical studies that reported on 4 or more patients, review articles, and experimental studies that concerned disease mechanisms were selected and further analyzed. Clinical reports that included fewer than 4 patients were selected only if they were believed to carry a significant message about disease mechanism or therapy. RESULTS Stevens-Johnson syndrome and toxic epidermal necrolysis seem to be variants of the same disease with differing severities. A widely accepted consensus regarding diagnostic criteria and therapy does not exist at present. Despite the recent experimental studies, the pathogenic mechanisms of these diseases remain unknown. Although progress in survival through early hospitalization in specialized burn units has been made, the prevalence of life-long disability from the ocular morbidity of Stevens-Johnson syndrome and toxic epidermal necrolysis has remained unchanged for the past 35 years. Further progress depends on modification of the acute phase of the disease rather than continuation of supportive care. The available published evidence indicates that a principal problem in the pathogenesis is immunologic and that immunomodulatory intervention with short-term, high-dose intravenous steroids or intravenous immunoglobulin holds the most promise for effective change in survival and long-term morbidity. CONCLUSIONS The results of this review call for a widely accepted consensus on diagnostic criteria for Stevens-Johnson and toxic epidermal necrolysis and multicenter collaboration in experimental studies and clinical trials that investigate disease mechanisms and novel therapeutic interventions, respectively.

Treatment of ocular inflammatory disorders with daclizumab

PURPOSE To evaluate the efficacy and safety of daclizumab therapy for patients with various ophthalmologic inflammatory disorders (all having previously failed standard treatment methods). DESIGN Retrospective, nonrandomized case series. PARTICIPANTS Fourteen patients. METHODS Fourteen patients were treated with daclizumab after previously failing standard treatment methods. MAIN OUTCOME MEASURES Inflammation and visual acuity. RESULTS Twelve of 27 (44%) eyes and 5 of 14 (36%) patients had improvement in visual acuity; 9 of 27 (33%) eyes and 5 of 14 (36%) patients had no change in visual acuity; and 6 of 27 (22%) eyes and 4 of 14 (27%) patients had continued visual loss. Based on degree of inflammation, 16 of 27 eyes (59%) had improvement, 3 of 27 (11%) eyes had no change, and 8 of 27 (30%) eyes worsened. CONCLUSIONS Daclizumab is safe and, at least in some patients, appears to be an effective medication in the treatment of ocular inflammatory disorders.

Wegener's Granulomatosis: Clinical Manifestations, Differential Diagnosis, and Management of Ocular and Systemic Disease

Wegeners granulomatosis (WG) is a systemic inflammatory disease whose histopathologic features often include necrosis, granuloma formation, and vasculitis of small-to-medium-sized vessels. WG involves many interrelated pathogenic pathways that are genetic, cell-mediated, neutrophil-mediated, humoral, and environmental. WG most commonly involves the upper respiratory tract, lungs, and kidneys, but has been reported to affect almost any organ. Ophthalmologic involvement is an important cause of morbidity in WG patients, occurring in approximately one-half of patients. The presence of unexplained orbital inflammatory disease, scleritis, peripheral ulcerative keratitis, cicatricial conjunctivitis, nasolacrimal duct stenosis, retinal vascular occlusion, or infrequently uveitis should raise the question of possible WG. A thorough clinical examination, laboratory testing, radiologic imaging, and histologic examination are essential to diagnosing WG and excluding potential mimics. Previously a uniformly fatal disease, treatment with cytotoxic and immunosuppressive agents has greatly improved survival. Treatment-related morbidity is a serious limitation of conventional therapies, leading to numerous ongoing studies of alternative agents.

Ocular syphilis among HIV-infected patients: a systematic analysis of the literature

Background Ocular syphilis among HIV-infected patients continues to be a problem in the highly active antiretroviral therapy (HAART) era. However, outside of case reports or small case series, little is known about the clinical, laboratory, and treatment outcomes of these patients. Objective To examine the literature on HIV-infected patients and determine the results of treatment. Methods Systematic review of cases series and case reports among HIV-infected individuals with ocular syphilis. Reviews, languages other than English and pre-1980 reports were excluded. The effect of CD4 count and virological suppression on clinical manifestations and diagnostic laboratory values was evaluated. Results A total of 101 HIV-infected individuals in case series and case reports were identified. Ocular syphilis led to the HIV diagnosis in 52% of cases, including patients with CD4 count >200 cells/mm3. Posterior uveitis was significantly more common in individuals with CD4 count <200 cells/mm3 (p=0.002). Three patients with confirmed ocular syphilis had negative non-treponemal tests. Ninety-seven per cent of patients with visual impairment improved following intravenous penicillin or ceftriaxone. Conclusions Non-treponemal tests may be negative in HIV-infected patients with ocular syphilis. Ocular syphilis remains an important clinical manifestation that can lead to initial HIV diagnosis.

Elevated Levels of Interleukin 6 in the Vitreous Fluid of Patients with Pars Planitis and Posterior Uveitis: The Massachusetts Eye & Ear Experience and Review of Previous Studies

Introduction: Although the exact mechanisms that lead to uveitis are not entirely known, the role of cytokines in the pathogenesis of this disease has been shown to be important. Prior studies described the presence of an array of cytokines in the intraocular fluid of patients with uveitis. Review of these studies indicate that Interleukin-6 (IL-6) is present, and animal data suggest the important role of IL-6 in the regulation of ophthalmologic immune responses. Purpose: We investigated whether IL-6, TNF-alpha, IL-1 alpha, beta, IL-2 are present in the vitreous of patients with active intermediate and posterior uveitis. Methods: Vitreous specimens were collected from 23 eyes of patients with active intermediate and posterior uveitis who underwent diagnostic or therapeutic vitrectomies. TNF-alpha, IL-1 alpha and beta, IL-2 and IL-6 were measured by enzyme-linked immunosorbent assay. Eight vitreous fluid samples from eye bank eyes were used as control. Results: IL-6 was higher in the vitreous of patients with uveitis compared to control samples (p = 0.0119). No TNF-alpha, IL-2, IL1-alpha or beta was detected. The levels of IL-6 did not correlate with a specific clinical diagnosis, but patients with pars planitis and panuveitis had the highest levels (p = 0.58) Conclusions: IL-6 is elevated in the vitreous of patients with active intermediate and posterior uveitis.

The use of biologic agents in the treatment of ocular manifestations of Behcet's disease.

Behçet’s Disease (BD) is a multisystem inflammatory disorder of uncertain etiology with a variety of potential manifestations throughout the body, and its ocular complications are some of its most devastating. Treatment with immunosuppressive agents has improved outcomes, but many patients suffer from disease that responds poorly to conventional therapies. Because of this, therapy with a variety of biological response modifiers has been employed. The earliest was interferon-α, and a multitude of reports have described its benefits for the uveitis associated with Behçet’s Disease. Many patients enjoy durable remissions of their ocular inflammatory disease even after discontinuation of therapy, but side-effects are almost universal and some can be dangerous. Of the newer biological response modifiers, infliximab, a monoclonal antibody to TNF-α, has been most extensively studied. It is reported to be rapidly effective in many cases of Behçet’s Disease uveitis, though with conflicting data as to the ability to induce durable remission after cessation of treatment. Side-effects are relatively rare, but may be serious. Several reports have been published on the use of other biologic agents, including adalimumab (a humanized antibody to TNF-α), etanercept (a molecule that resembles the TNF-α receptor), and rituximab (an antibody to CD20 that depletes the body of CD20-positive B cells). Of the three of these, adalimumab has the most promising initial evidence, etanercept has very few positive reports in patients with BD uveitis (and is likely ineffective in uveitis in general), and rituximab is lacking data. Although randomized controlled trials are almost completely lacking, currently available evidence is promising that biologic agents can prove an invaluable addition to the armamentarium of the practitioner treating patients with BD uveitis.

Keratoprosthesis in Autoimmune Disease

Purpose: To describe the clinical features and course of 2 patients with autoimmune diseases and their experience with the Boston keratoprosthesis. To draw on general medical literature to try to better understand recurrent complications. Methods: Retrospective review of 2 patients treated with Boston keratoprostheses. The clinical histories, examinations, and other diagnostics were reviewed. A literature review was performed. Results: The first patient presented with end-stage ocular disease secondary to toxic epidermal necrolysis (TENS). The second patient presented with end-stage ocular disease secondary to mucous membrane pemphigoid (MMP). Both patients underwent treatment with the Boston keratoprosthesis. Both patients suffered numerous corneal melts requiring multiple repeat implantations. Conclusions: Patients with corneal blindness secondary to autoimmune disease often fare poorly with available surgical treatments. Study of existing literature on prosthetic device complications in autoimmune diseases may help uncover common mechanisms of tissue destruction to establish perioperative immunomodulatory regimens targeted to specific underlying diseases.

Ocular syphilis among HIV-infected individuals

We describe a human immunodeficiency virus (HIV)-infected individual with ocular manifestations of secondary syphilis. Twelve other cases of HIV-associated ocular syphilis are also presented. Six of 12 individuals had normal cerebrospinal fluid study results, and 3 patients required retreatment within 1.5 years. In patients with HIV infection, clinicians should be vigilant for ocular syphilis despite normal cerebrospinal fluid measures and for syphilis reinfection.

Treatment of seronegative spondyloarthropathy-associated uveitis with golimumab: retrospective case series.

not have a high resolution. The quality of the images was sufficient to visualize the iris abnormalities in the present cases, however. For cases in which more detailed images might be required, an infrared slit-lamp biomicroscope might prove more appropriate. The flexibility of the mobile camera allowed us to observe an infant and a small child, for whom slit-lamp microscopy and slit-lamp photography are more problematic. This system is also likely to prove beneficial for the observation of pupil shape before keratoplasty in bullous keratopathy patients with an unknown clinical history. Such observation may facilitate identification of a peaked pupil because of vitreous prolapse into the side port or the corneal or sclerocorneal tunnel. On the other hand, we found that although the shape of the pupil of patients with a scarred cornea was visible with the Meibopen camera, it was not as clear as that for individuals with an oedematous cornea (data not shown). Unlike the case of corneal oedema, the corneal opacity associated with a scarred cornea is not due to disorganization of collagen fibres but rather is the result either of abnormal collagen fibres secreted by fibroblasts or myofibroblasts, or of the loss of transparency of corneal stromal cells. The benefits of infrared observation are thus likely to be restricted to oedematous corneas. We have thus demonstrated the novel application of an infrared anterior segment camera to observation of the condition of the iris that is masked by the corneal opacity because of stromal oedema in patients with Peters’ anomaly. This non-invasive approach provides valuable clinical information and should prove applicable to other conditions characterized by corneal stromal oedema.

The Genetics of Adamantiades-Behcet's Disease

Adamanitiades-Behcets disease (ABD) is a relapsing systemic vasculitis that may involve the eyes, skin, and almost all other organ systems. Current research on the pathogenesis of ABD suggests a genetic basis for the disease, with certain MHC genes such as those coding for HLA-B51 being the most obvious candidates. Environmental factors such as infectious disease are thought to be responsible for triggering an immunological reaction and systemic features of the disease in genetically susceptible individuals. Identification of genes responsible for this susceptibility may lead to more definitive diagnostic tests and new approaches to the management of this potentially blinding condition.