Clonal cutaneous and neurosyphilis: A pitfall in pseudolymphoma diagnosis.

Syphilis is a sexually transmitted infectious disease caused by the bacterium Treponema pallidum and can cause a wide variety of cutaneous manifestations, most commonly, a papulosquamous eruption of the trunk and extremities. Treatment with penicillin is curative. We report a case of a 69-year-old man who presented with recent onset of blurry vision and a nonpainful, nonpruritic eruption of pink-to-violaceous dermal nodules on his upper trunk and upper extremities. Biopsies of two separate locations revealed a dense superficial and deep perivascular atypical lymphocytic infiltrate with admixed plasma cells, histiocytes, and eosinophils. Some scattered cells expressed CD30, PD1, BCL-6, and ICOS. T-cell receptor (TCR)-rearrangement showed an identical TCR-gamma clone between both biopsy specimens. The patient was subsequently seen by ophthalmology and diagnosed with acute anterior uveitis. Rapid plasma reagin was reactive and cerebrospinal fluid studies showed findings consistent with a diagnosis of neurosyphilis. A T. pallidum immunostain of the skin biopsies was performed upon re-review, and was diffusely positive for spirochetes at the dermal-epidermal junction and within injured vessels. The patient was treated with penicillin G with near-resolution of his skin lesions. This case highlights the unusual ability of syphilis to mimic a T-cell lymphoma with matching clones across two different biopsy sites.

Chronic Unilateral Uveitis as a Manifestation of Leprosy: A Case Report and Literature Review.

Purpose: To describe a case of leprosy presenting chronic anterior uveitis associated with other systemic lesions.Methods: Case report and systematic literature review.Results: We describe the case of a 65-year-old patient presenting clinical features of chronic uveitis and poor response to topical and intravitreal steroid treatment. Upon ocular examination, diffuse iris atrophy and macular edema were observed and laboratory tests for autoimmune and infectious diseases were within normal range. Physical examination revealed the presence of skin lesions on trunk and extremities, which were biopsied and identified as positive for leprosy.Conclusion: The case reported herein presented atypical characteristics of uveitis due to the involvement of the posterior segment of the eye. Leprosy diagnosis could be a challenge, a systematic approach is mandatory to achieve adequate treatment.

Collaborative Ocular Tuberculosis Study Consensus Guidelines on the Management of Tubercular Uveitis-Report 2: Guidelines for Initiating Antitubercular Therapy in Anterior Uveitis, Intermediate Uveitis, Panuveitis, and Retinal Vasculitis.

TOPIC: The Collaborative Ocular Tuberculosis Study (COTS), supported by the International Ocular Inflammation Society, International Uveitis Study Group, and Foster Ocular Immunological Society, set up an international, expert-led consensus project to develop evidence- and experience-based guidelines for the management of tubercular uveitis (TBU). CLINICAL RELEVANCE: The absence of international agreement on the use of antitubercular therapy (ATT) in patients with TBU contributes to a significant heterogeneity in the approach to the management of this condition. METHODS: Consensus statements for the initiation of ATT in TBU were generated using a 2-step modified Delphi technique. In Delphi step 1, a smart web-based survey based on background evidence from published literature was prepared to collect the opinion of 81 international experts on the use of ATT in different clinical scenarios. The survey included 324 questions related to tubercular anterior uveitis (TAU), tubercular intermediate uveitis (TIU), tubercular panuveitis (TPU), and tubercular retinal vasculitis (TRV) administered by the experts, after which the COTS group met in November 2019 for a systematic and critical discussion of the statements in accordance with the second round of the modified Delphi process. RESULTS: Forty-four consensus statements on the initiation of ATT in TAU, TIU, TPU, and TRV were obtained, based on ocular phenotypes suggestive of TBU and corroborative evidence of tuberculosis, provided by several combinations of immunologic and radiologic test results. Experts agreed on initiating ATT in recurrent TAU, TIU, TPU, and active TRV depending on the TB endemicity. In the presence of positive results for any 1 of the immunologic tests along with radiologic features suggestive of past evidence of tuberculosis infection. In patients with a first episode of TAU, consensus to initiate ATT was reached only if both immunologic and radiologic test results were positive. DISCUSSION: The COTS consensus guidelines were generated based on the evidence from published literature, specialists' opinions, and logic construction to address the initiation of ATT in TBU. The guidelines also should inform public policy by adding specific types of TBU to the list of conditions that should be treated as tuberculosis.

Earlier use of systemic immunosuppression is associated with fewer ophthalmic surgeries in paediatric non-infectious uveitis.

BACKGROUND/AIMS: There is a paucity of large trials investigating the effect of management strategies for paediatric non-infectious uveitis on complications requiring surgery. The purpose of our study is to investigate whether earlier initiation of systemic immunosuppression in paediatric non-infectious uveitis is associated with fewer ophthalmic surgeries. METHODS: A retrospective review was conducted on 48 children with non-infectious uveitis assessed in 1998-2013. Patients were divided into uveitis diagnosed before December 2008 (group 1) and after January 2009 (group 2). Duration from uveitis onset to methotrexate initiation (U-MTX) and biological addition (U-Biologic) were reviewed. Follow-up visits with topical corticosteroids >3 times daily and active uveitis (≥1+ cells) during 3.5 years were documented. The main outcome measure was the need for ≥1 ophthalmic surgery at 3.5 years. RESULTS: In group 1, 69.5% of patients required ≥1 ophthalmic surgery at 3.5 years versus 26.9% in group 2 (p=0.005). U-MTX was 28.9±11.8 weeks and 14.2±10.0 weeks for groups 1 and 2 (p=0.028). U-Biologic was 134.6±46.0 weeks and 82.3±43.3 weeks for groups 1 and 2 (p=0.0016). Corticosteroid use >3 times daily was 85.9±52.7 weeks and 14.6±11.1 weeks for groups 1 and 2. Multivariate regression showed methotrexate initiation within 6 months of uveitis onset lowered the likelihood of needing ophthalmic surgery at 3.5 years (OR=6.2, 95% CI 1.2 to 33.4; p=0.033). Univariate regression demonstrated biological addition within 18 months of uveitis onset reduced the likelihood of requiring ophthalmic surgery (OR 12.57, 95% CI 1.28 to 123.48; p=0.030). CONCLUSION: Earlier control of uveitis by addition of immunosuppressive therapy reduced the need for ophthalmic surgery.

Case Report: Bilateral Granulomatous Anterior Uveitis in HIV-patient with Disseminated Talaromycosis (penicilliosis) Marneffei Infection.

We report on a 22-years-old Thai male patient with congenital HIV infection. Due to his non-adherence to antiretroviral treatment he developed disseminated Talaromyces marneffei infection and was treated with intravenous amphotericin B. Despite this treatment, he presented with bilateral granulomatous anterior uveitis. Uveitis improved only after intracameral injection of amphotericin B.

Recent Developments in HLA B27 Anterior Uveitis.

There has been steady progress in understanding the pathogenesis, clinical features, and effective treatment of acute anterior uveitis (AU) over the past 5 years. Large gene wide association studies have confirmed that AU is a polygenic disease, with overlaps with the seronegative arthropathies and inflammatory bowel diseases, associations that have been repeatedly confirmed in clinical studies. The role of the microbiome in AU has received increased research attention, with recent evidence indicating that human leukocyte antigen B27 (HLA B27) may influence the composition of the gut microbiome in experimental animals. Extensive clinical investigations have confirmed the typical features of acute AU (AAU) and its response to topical, regional and systemic immunosuppressive treatment. Increased understanding of the role of cytokines has resulted in studies confirming the value of anti-cytokine therapy [anti-tumor necrosis factor (anti-TNF) and interleukin 6 (IL-6) therapy] in severe and recurrent cases of AAU, particularly in subjects with an associated spondyloarthopathy (SpA) and in juvenile idiopathic arthritis (JIA)-associated AAU.

Supposed endogenous endophthalmitis caused by Serratia marcescens in a cat.

An 8-year-old male neutered domestic shorthair cat was presented for evaluation of acute respiratory distress. Respiratory auscultation revealed a diffuse and symmetric increase in bronchovesicular sounds. Thoracic radiographs showed a diffuse unstructured interstitial pulmonary pattern with multifocal alveolar foci. Despite an aggressive treatment with supportive care, including oxygenotherapy and systemic antibiotics, progressive respiratory distress increased. Three days after the presentation, acute anterior uveitis was noticed on left eye. Ophthalmic examination and ocular ultrasonography revealed unilateral panuveitis with ocular hypertension. The right eye examination was unremarkable. Cytological examination of aqueous humor revealed a suppurative inflammation. Serratia marcescens was identified from aqueous humor culture. Primary pulmonary infection was suspected but was not confirmed as owners declined bronchoalveolar lavage. Active uveitis resolved and cat's pulmonary status improved after appropriate systemic antibacterial therapy. Vision loss was permanent due to secondary mature cataract. To the best of authors' knowledge, this is the first report of endogenous bacterial endophthalmitis secondary to S. marcescens infection in a cat.

Ophthalmologic findings associated with Rhodococcus equi bronchopneumonia in foals.

OBJECTIVE: To describe ocular findings associated with Rhodococcus equi bronchopneumonia in foals, and to determine whether severity of the ocular lesions is related with outcome. ANIMALS STUDIED: Foals diagnosed with R equi infection at the VTH-UAB from January 2002 to December 2017. PROCEDURE: Rhodococcus equi infection was diagnosed by means of clinical signs, radiographic/ultrasonographic findings, and/or positive culture. In all the foals, a complete ophthalmic examination by a boarded ophthalmologist was performed and ocular signs were recorded and graded (0-4). RESULTS: Thirty-nine foals were included in the study, from which 12 showed signs of bilateral anterior uveitis (30.8%). Among these, three foals were classified as mildly uveitis-affected (MUA:7.7%) and nine as severely uveitis-affected (SUA:23.1%). Five SUA foals showed green aqueous flare (5/9;55.5%). Despite the systemic treatment, 9/39 sick foals died (23.1%), the fatality rate being different between groups: SUA (4/9;44.4%), MUA (0/3; 0%) and nonuveitis-affected foals (5/27;18.5%). Among SUA foals, only one with green aqueous flare died (1/5;20%). CONCLUSION: Bilateral anterior uveitis is highly prevalent in foals with R equi pneumonia (30.8%). The severity of anterior uveitis might be considered a nonsurvival prognostic factor and, until proven otherwise, green aqueous flare could be taken as a strongly suggestive ocular sign of the disease. Findings of this study remark the clinical relevance of performing a complete ophthalmic examination in sick foals, in order to help in the diagnosis and prognosis of uveal diseases, as well as to guaranteeing visual soundness.

The microbiome and HLA-B27-associated acute anterior uveitis.

Acute anterior uveitis (AAU) and the spondyloarthritis (SpA) subtypes ankylosing spondylitis, reactive arthritis and psoriatic arthritis are among the inflammatory diseases affected by the biology of the intestinal microbiome. In this Review, the relationship between AAU, SpA and the microbiome is discussed, with a focus on the major SpA risk gene HLA-B*27 and how it is associated with both intestinal tolerance and the loss of ocular immune privilege that can accompany AAU. We provide four potential mechanisms to account for how dysbiosis, barrier function and immune response contribute to the development of ocular inflammation and the pathogenesis of AAU. Finally, potential therapeutic avenues to target the microbiota for the clinical management of AAU and SpA are outlined.

Raised intracranial pressure with bilateral anterior uveitis.

We report the rare case of a 5-year-old boy with an infective cause of papilloedema and bilateral uveitis secondary to Mycoplasma pneumoniae The patient presented with generalised headache and malaise. MRI showed signs of raised intracranial pressure and lumbar puncture opening pressure was 43 cmH2O.Lumbar puncture did not reveal any infective organisms. Blood tests showed raised inflammatory markers. The patient was started on prednisolone, acetazolamide and intravenous cefotaxime. Following an improvement, the patient was discharged.However, the patient re-presented 2 weeks later with bilateral anterior uveitis. With the combination of papilloedema and bilateral uveitis, M. pneumoniae infection was suspected. Tests confirmed recent mycoplasma infection. Topical dexamethasone and oral azithromycin were given and symptoms improved.Vision remained normal throughout. At 1-year follow-up, the patient remains well. The authors would like to highlight a rare infectious cause of papilloedema in young children.

Ocular manifestations of rickettsia in children: common but frequently overlooked.

We review two cases of ocular manifestations of Rickettsia conorii infection in children. A girl who presented unilateral visual loss with focal retinitis and macular oedema and a boy with unilateral central scotoma and bilateral anterior uveitis. Progressive functional and anatomic recovery was observed after oral antibiotics and steroids were initiated.

Immune stromal keratitis: a rare ocular presentation of tuberculosis.

An 11-year-old female patient presented with diminution of vision in both the eyes for the last 4 days. She had redness, watering and photophobia for the past 11 days. Slit lamp examination revealed multiple disc-shaped corneal stromal infiltrates with an overlying epithelial defect and hypopyon in both the eyes. A provisional diagnosis of infective keratitis was made. The patient was started on empirical antimicrobial therapy. However, no improvement was noted over the next 72 hours. Microbiological examination of the corneal scraping from both the eyes was negative. Considering the above, provisional diagnosis was changed to immune stromal keratouveitis and the patient was started on topical steroids. Further evaluation revealed a positive Mantoux test (30×20 mm) and contrast enhanced CT chest showing pulmonary nodules, suggestive of tuberculosis. The patient was subsequently started on antitubercular treatment. The infiltrates along with the ulcer and anterior uveitis responded dramatically to the revised treatment and resolved completely within 7 days of therapy.

Gut Microbiota Composition and Fecal Metabolic Phenotype in Patients With Acute Anterior Uveitis.

Purpose: To investigate gut microbiota composition and fecal metabolic phenotype in patients with acute anterior uveitis. Methods: Fecal DNA was extracted from 78 fecal samples (38 acute anterior uveitis (AAU) patients and 40 family members of patients or sex- and age-matched healthy controls) and then sequenced by high-throughput 16S rDNA analysis. Gas chromatographic mass spectrometry (GC-MS) based metabolomics was performed on 60 fecal samples (30 AAU patients and 30 healthy controls). Results: A significant difference was observed in beta diversity between AAU patients and healthy controls. Eight genera including Roseburia were reduced in AAU patients, and Veillonella was increased in AAU patients as compared with healthy controls. Significance was however lost after false discovery rate (FDR) correction. The expression of seven fecal metabolites including 6-deoxy-D-glucose 1, linoleic acid, N-Acetyl-beta-D-mannosamine 3, shikimic acid, azelaic acid, isomaltose 1 and palmitoleic acid was increased in AAU patients. Linoleic acid showed a significant correlation with Roseburia and Veillonella according to Spearman correlation analysis. Conclusions: Our results did not reveal a difference in gut microbiota composition, but did show that the fecal metabolic phenotype in AAU patients was significantly different from healthy controls.

Clinical Profile of Patients with Tubercular Subretinal Abscess in a Tertiary Eye Care Center in Southern India.

PURPOSE: To retrospectively analyze clinical features, laboratory investigations, treatment and visual outcomes in patients with tubercular subretinal abscess. METHODS: A total of 12 eyes of 12 patients receiving a diagnosis of subretinal abscess, between 2004 and 2014, were included for this retrospective study. RESULTS: The mean age of the presentation was 29.75 ± 16.72 years (range: 14-62 years) and seven (58.3%) were male. The most common anterior segment presentation was anterior uveitis (75%). The mean BCVA at presentation was 1.62 (in logMAR). A tuberculin skin test was positive in seven patients (58.3%) and five patients had a history of pulmonary tuberculosis. Polymerase chain reaction for the Mycobacterium tuberculosis genome was positive in 6 of 11 eyes from aqueous aspirate (54%) and 4 of 7 eyes from vitreous aspirates (57.14%). All patients were started on systemic steroids and an anti-tubercular regimen. The mean duration of follow-up was 134.28 days. The mean BCVA at final presentation was 1.19 (in logMAR). Chorioretinal scar was the most common finding after resolution. CONCLUSIONS: Subretinal abscess is a rare manifestation of ocular tuberculosis. A high degree of suspicion and timely management of the condition can prevent loss of vision.

Acute Mycoplasma pneumoniae infection presenting with unilateral anterior uveitis and perineuritis.

We report a case of confirmed Mycoplasma pneumoniae infection in the setting of unilateral anterior uveitis and perineuritis without coexisting systemic manifestations. We hypothesize a causal association between acute M. pneumoniae infection and this patient's ocular presentation. Delay in identification of M. pneumoniae infection in this case prompted treatment with systemic and topical steroids for presumed autoimmune etiology. The rapid resolution of symptoms without concurrent antibiotic treatment suggests a possible postinfectious autoimmune component that may be responsive to steroid treatment.

Nongranulomatous Uveitis as the First Manifestation of Syphilis.

PURPOSE: The incidence of syphilis appears to be increasing in recent years. Although any structure of the eye can be involved in syphilis, isolated unilateral anterior uveitis as an initial sign of the disease is rare. We report a case of ocular syphilis presenting as a mild unilateral, nongranulomatous, anterior uveitis in an otherwise asymptomatic patient. CASE REPORT: A 64-year-old white male patient presented with a 3-day history of mildly reduced vision, photophobia, and pain in his left eye. The patient denied prior occurrences, and no contributing ocular or medical history was elicited. Entering corrected distance acuities were 20/25+ in the right eye and 20/20- in the left eye. Slit lamp examination of the left eye revealed a moderate circumlimbal flush, numerous fine keratic precipitates, and mild-to-moderate white blood cells in the anterior chamber. The patient was diagnosed as having acute, idiopathic, nongranulomatous, anterior uveitis, and topical steroid/cycloplegic treatment was initiated. Despite an initially positive, although somewhat sluggish response to treatment, the patient's uveitis suddenly worsened on day 44, exhibiting increased anterior chamber cells, several mutton-fat keratic precipitates, and elevated intraocular pressure. Systemic diagnostic workup led to the diagnosis of neurosyphilis, and the patient subsequently admitted to high-risk sexual behaviors. Treatment with intravenous aqueous penicillin-G 24 million units per day for 14 days led to complete resolution of uveitis. The case was reported to the local health department within 24 h of syphilis diagnosis. CONCLUSIONS: Syphilis, although an uncommon cause of ocular inflammation, is a highly contagious, but curable disease. Given its potentially devastating neurologic consequences, syphilis should be considered in all patients presenting with uveitis. A high index of clinical suspicion and a detailed sexual history are crucial for the accurate and timely diagnosis of ocular syphilis.

Does the Microbiome Cause B27-related Acute Anterior Uveitis?

The microbiome is strongly implicated in a broad spectrum of immune-mediated diseases. Data support the concept that HLA molecules shape the microbiome. We provide hypotheses to reconcile how HLA-B27 might affect the microbiome and in turn predispose to acute anterior uveitis. These theories include bacterial translocation, antigenic mimicry, and dysbiosis leading to alterations in regulatory and effector T-cell subsets. Received 31 October 2015; revised 7 January 2016; accepted 8 January 2016; published online 22 March 2016.

Levofloxacin and Tobramycin for Severe Bacterial Keratouveitis.

PURPOSE: To report on clinical features and outcome of severe bacterial keratouveitis. METHODS: Twenty patients with severe bacterial keratouveitis treated with topical tobramycin and levofloxacin and oral levofloxacin were included. Main outcome measures were ulcers location, bacterial isolates, risk factors, visual prognosis. RESULTS: Centrally located ulcer/abscess was present in 65% of patients. Contact lens (CL) wear was the most common risk factor (70%). Bacterial isolates were observed in 58% of patients, none resistant to tobramycin and levofloxacin. Pseudomonas aeruginosa was found in 47% of positive cases and in 64% of CL wearers. After therapy, the mean visual acuity improved significantly (p < 0.0001), particularly in contact lens wearers (p = 0.04) and in patients younger than 60 years old (p < 0.001). CONCLUSIONS: Pseudomonas aeruginosa is the most frequent cause of bacterial keratouveitis and CL wear the most common risk factor. Topical tobramycin and levofloxacin and oral levofloxacin are effective in the treatment of bacterial keratouveitis.

The Rate of Helicobacter pylori Seropositivity in a Group of Korean Patients with HLA-B27-Associated Acute Anterior Uveitis.

PURPOSE: To investigate an association between Helicobacter pylori seropositivity and HLA-B27-positive acute anterior uveitis (AAU) in Korean patients. METHODS: Retrospective analysis was performed with data from 106 patients previously diagnosed with AAU without clinical evidence of spondyloarthropathy. Serum immunoglobulin G antibodies to H. pylori were measured by enzyme-linked immunosorbent assay, and HLA typing was performed using polymerase chain reaction of DNA amplification. We included 72 non-uveitis patients and 35 age- and sex-matched healthy controls in the study. RESULTS: Of the 106 patients with AAU, 41 (38.7%) were HLA-B27-positive, and 45 (42.5%) were seropositive for H. pylori. Patients with HLA-B27-positive AAU had a significantly lower prevalence of H. pylori seropositivity compared to those with HLA-B27-negative AAU and healthy controls (24.4% vs. 53.8%, p = 0.003; 24.4% vs. 57.1%, p = 0.004, respectively). In the non-uveitis group, however, HLA-B27-positive patients exhibited similar H. pylori seropositivity prevalence to HLA-B27-negative patients and healthy controls (45.5% vs. 55.7%, p = 0.529; 45.5% vs. 57.1%, p = 0.497, respectively). In multivariate analysis, a low prevalence of H. pylori seropositivity was significantly associated with HLA-B27-positive AAU (odds ratio = 0.340, 95% confidence interval 0.135-0.855, p = 0.022). CONCLUSIONS: Our results suggest an inverse association between H. pylori seropositivity and HLA-B27-positive AAU. Further investigation of this association is needed, given the low prevalence of H. pylori seropositivity observed in patients with HLA-B27-positive AAU.

Granulomatous uveitis and reactive arthritis as manifestations of post-streptococcal syndrome.

To report a case of bilateral granulomatous post-streptococcal syndrome uveitis in association with reactive arthritis as manifestation of post-streptococcal syndrome. To our knowledge, this could represent the first reported case in the literature. A 9-year-old girl, with no past ocular history, presented with a 5-day history of bilateral blurred vision, red eyes, photophobia and walking difficulties because of a right ankle pain. Ophthalmic examination disclosed a visual acuity limited to hand motion, mutton-fat keratic precipitates, anterior chamber cells and posterior synechiae in both eyes. Ocular pressure was normal. Physical examination showed a fever (38 °C), inflammatory ankle arthritis and scarlet fever (streptococcal lesion). Anti-streptococcal lysine O titer was 419 µ/ml. The patient was treated with topical steroids, cycloplegics, high-dose oral steroids and preventive course of penicillin with total improvement and no recurrence. Post-streptococcal syndrome should be considered in the etiology of acute bilateral granulomatous uveitis in children, and anti-streptococcal lysine O titer should be considered in serodiagnostic testing.