Extranodal Rosai-Dorfman disease manifesting as Sjögren's syndrome combined with panuveitis and hypertrophic pachymeningitis: a case report and review of literature.

Rosai-Dorfman disease (RDD) is a rare non-Langerhans cell histiocytosis characterized by massive lymphadenopathy and systemic extranodal lesions. We present the case of a 28-year-old woman who presented with recurrent blurred vision in her right eye for 3 months. She developed blindness and atrophy in her left eye a decade prior to presentation. She subsequently developed headache, fever, and impaired mental status. Cranial magnetic resonance imaging indicated hypertrophic pachymeningitis (HP), and 18F-fluoro-2-deoxy-2-d-glucose (FDG) positron emission tomography/computed tomography revealed significant FDG uptake in the left dura mater. Autoimmune testing revealed elevated anti-nuclear, anti-SS-A, and anti-SS-B antibody levels. Incisional biopsy of the atrophic eyeball revealed RDD with marked polyclonal plasmacytosis. The patient was diagnosed with RDD accompanied by multisystem involvement, including Sjögren's syndrome (SS), panuveitis, and HP. Treatment with methylprednisolone for several weeks resulted in significant improvement. This is the first reported case of RDD presenting with SS in combination with panuveitis and HP. Although RDD is rarely diagnosed in young patients, interdisciplinary collaboration is essential to prevent a delayed diagnosis.

Diagnostic Challenges in PD-1 Inhibitor Induced Panuveitis in a Teenage Girl with Chest Soft Tissue Sarcoma - A Case Report.

PURPOSE: To report a case of programmed cell death receptor-1 (PD-1) inhibitor induced panuveitis. METHOD: Observational case report of a 13-year-old Chinese girl presented as panuveitis. The clinical course, imaging performance, laboratory examination, differential diagnosis, treatment and prognosis were described. RESULT: Patient presented with bilateral anterior granulomatous uveitis, vitritis, papillitis, and various creamy yellow nodular lesions in the mid-peripheral fundus. She had a history of biopsy proven alveolar soft tissue sarcoma on the chest wall and pulmonary metastasis, and a PD-1 inhibitor (sintilimab) was intravenously administered. Blood tests, magnetic resonance imaging of the cranium and the orbit, aqueous humor assay of inflammatory cytokines and microbial DNA were performed to distinguish infectious and non-infectious uveitis, choroidal metastases, and intravenous injection-related endophthalmitis. The oncologist evaluated that the sarcoma was stable and terminated sintilimab dosage. After sintilimab withdrawal, the blurred vision improved. Then, the patient received oral corticosteroids, resulted in resolution of the panuveitis. A diagnosis of PD-1 inhibitor induced panuveitis was made. CONCLUSION: For patients taking PD-1 inhibitors, the major diagnostic challenge is to identify whether the cause of the uveitis is due to the antitumor treatment or not. It is suggested to be screened by eye care specialist and timely referral to uveitis specialist with any suspicion of intraocular inflammation for these patients.

Unusual Presentation of Skin Tattoo-Associated Panuveitis.

AIM: We report a case of a young male who developed bilateral panuveitis after extensive tattooing. DESIGN: Case report. METHODS: A 22-year-old male with a history of inflamed tattoos presented with pain in both eyes and blurred vision in the left eye. Clinical examination showed ciliary congestion, flare, vitreous cells in both eyes, and posterior synechiae in the left eye. Optic nerve was swollen in both eyes. OCT scans demonstrated subretinal blood, associated with neurosensory macular detachment in the left eye. The skin tattoo biopsy showed a granulomatous inflammation without evidence of sarcoidosis. Long-term corticosteroid therapy allowed a regression of clinical signs and symptoms with full recovery. CONCLUSION: TAttoo Granulomas with Uveitis (TAGU) is a syndrome with numerous clinical presentations. In our case, optic nerve head oedema and subretinal hemorrhage at the posterior pole were the presentation signs. Ophthalmologists should always consider TAGU as a diagnosis in patients with a history of inflamed tattoos.

Non-biologic, steroid-sparing therapies for non-infectious intermediate, posterior, and panuveitis in adults.

BACKGROUND: Non-infectious intermediate, posterior, and panuveitis (NIIPPU) represent a heterogenous collection of autoimmune and inflammatory disorders isolated to or concentrated in the posterior structures of the eye. Because NIIPPU is typically a chronic condition, people with NIIPPU frequently require treatment with steroid-sparing immunosuppressive therapy. Methotrexate, mycophenolate, cyclosporine, azathioprine, and tacrolimus are non-biologic, disease-modifying antirheumatic drugs (DMARDs) which have been used to treat people with NIIPPU. OBJECTIVES: To compare the effectiveness and safety of selected DMARDs (methotrexate, mycophenolate mofetil, tacrolimus, cyclosporine, and azathioprine) in the treatment of NIIPPU in adults. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register), MEDLINE, Embase, the Latin American and Caribbean Health Sciences database, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform, most recently on 16 April 2021. SELECTION CRITERIA: We included randomized controlled trials (RCTs) comparing selected DMARDs (methotrexate, mycophenolate, tacrolimus, cyclosporine, and azathioprine) with placebo, standard of care (topical steroids, with or without oral steroids), or with each other. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included 11 RCTs with a total of 601 participants in this review. DMARDs versus control Two studies compared an experimental DMARD (cyclosporine A or enteric-coated mycophenolate [EC-MPS]) plus oral steroid with steroid monotherapy. We did not pool these results into a meta-analysis because the dose of cyclosporine used was much higher than that used in current clinical practice. The evidence is very uncertain about whether EC-MPS plus low-dose oral steroid results in a higher proportion of participants achieving control of inflammation over steroid monotherapy (risk ratio [RR] 2.81, 95% confidence interval [CI] 1.10 to 7.17; 1 study, 41 participants; very low-certainty evidence). The change in best-corrected visual acuity (BCVA) was reported separately for right and left eyes. The evidence for improvement (lower logarithm of the minimum angle of resolution (logMAR) indicates better vision) between the groups is very uncertain (mean difference [MD] -0.03 and -0.10, 95% CI -0.96 to 0.90 and -0.27 to 0.07 for right and left, respectively; 1 study, 82 eyes; very low-certainty evidence). No data were available for the following outcomes: proportion of participants achieving a 2-line improvement in visual acuity, with confirmed macular edema, or achieving steroid-sparing control. The evidence for the proportion of participants requiring cessation of medication in the DMARD versus control group is very uncertain (RR 2.61, 95% CI 0.11 to 60.51; 1 study, 41 participants; very low-certainty evidence). Methotrexate versus mycophenolate We were able to combine two studies into a meta-analysis comparing methotrexate versus mycophenolate mofetil. Methotrexate probably results in a slight increase in the proportion of participants achieving control of inflammation, including steroid-sparing control, compared to mycophenolate at six months (RR 1.23, 95% CI 1.01 to 1.50; 2 studies, 261 participants; moderate-certainty evidence). Change in BCVA was reported per eye and the treatments likely result in little to no difference in change in vision (MD 0.01 logMAR higher [worse] for methotrexate versus mycophenolate; 2 studies, 490 eyes; moderate-certainty evidence). No data were available for the proportion of participants achieving a 2-line improvement in visual acuity. The evidence is very uncertain regarding the proportion of participants with confirmed macular edema between methotrexate versus mycophenolate (RR 0.49, 95% CI 0.19 to 1.30; 2 studies, 35 eyes; very low-certainty). Methotrexate versus mycophenolate may result in little to no difference in the proportion of participants requiring cessation of medication (RR 0.99, 95% CI 0.43 to 2.27; 2 studies, 296 participants; low-certainty evidence). Steroids with or without azathioprine versus cyclosporine A Four studies compared steroids with or without azathioprine (oral steroids, intravenous [IV] steroids, or azathioprine) to cyclosporine A. We excluded two studies from the meta-analysis because the participants were treated with 8 mg to 15 mg/kg/day of cyclosporine A, a significantly higher dose than is utilized today because of concerns for nephrotoxicity. The remaining two studies were conducted in all Vogt-Koyanagi-Harada disease (VKH) populations and compared cyclosporine A to azathioprine or IV pulse-dose steroids. The evidence is very uncertain for whether the steroids with or without azathioprine or cyclosporine A influenced the proportion of participants achieving control of inflammation (RR 0.84, 95% CI 0.70 to 1.02; 2 studies, 112 participants; very low-certainty evidence), achieving steroid-sparing control (RR 0.64, 95% CI 0.33 to 1.25; 1 study, 21 participants; very low-certainty evidence), or requiring cessation of medication (RR 0.85, 95% 0.21 to 3.45; 2 studies, 91 participants; very low-certainty evidence). The evidence is uncertain for improvement in BCVA (MD 0.04 logMAR lower [better] with the steroids with or without azathioprine versus cyclosporine A; 2 studies, 91 eyes; very low-certainty evidence). There were no data available (with current cyclosporine A dosing) for the proportion of participants achieving a 2-line improvement in visual acuity or with confirmed macular edema. Studies not included in synthesis We were unable to include three studies in any of the comparisons (in addition to the aforementioned studies excluded based on historic doses of cyclosporine A). One was a dose-response study comparing cyclosporine A to cyclosporine G, a formulation which was never licensed and is not clinically available. We excluded another study from meta-analysis because it compared cyclosporine A and tacrolimus, considered to be of the same class (calcineurin inhibitors). We were unable to combine the third study, which examined tacrolimus monotherapy versus tacrolimus plus oral steroid, with any group. AUTHORS' CONCLUSIONS: There is a paucity of data regarding which DMARD is most effective or safe in NIIPPU. Studies in general were small, heterogenous in terms of their design and outcome measures, and often did not compare different classes of DMARD with each other. Methotrexate is probably slightly more efficacious than mycophenolate in achieving control of inflammation, including steroid-sparing control (moderate-certainty evidence), although there was insufficient evidence to prefer one medication over the other in the VKH subgroup (very low-certainty evidence). Methotrexate may result in little to no difference in safety outcomes compared to mycophenolate.

Cooperation with rheumatologists on intensive systemic treatment for psoriatic arthritis-related panuveitis with retinal vasculitis: a case report.

BACKGROUND: Patients with psoriatic arthritis (PsA) may develop uveitis, a potentially serious ocular complication. PsA-related uveitis may result in significant morbidity and even vision loss if underdiagnosed or under-treated. We presented a case with long-standing recurrent uveitis and retinal vasculitis successfully managed by fortified systemic immunomodulators for systemic PsA. CASE PRESENTATION: A 47-year-old woman was referred under the impression of acute anterior uveitis in her right eye in recent one month. Ocular examinations showed panuveitis in both eyes with intense vitreous opacity in her right eye. Fundus fluorescence angiography revealed retinal vasculitis in both eyes. Systemic surveys excluded the possibility of infection but showed an elevated inflammation marker. With intensive immunosuppressive treatment, inflammation resolved and the vision improved. CONCLUSION: Our case highlights not only the importance of intensified systemic therapy in treating PsA-related uveitis but the importance of multidisciplinary collaboration. Recurrent uveitis may be an indicator of disease activity prior to other inflammatory markers.

Extranodal natural killer/T-cell lymphoma presenting as hypopyon panuveitis: a case report.

BACKGROUND: Extranodal natural killer/T-cell lymphoma (ENKTL), nasal type, generally affects the orbit by direct extension. It can even rarely present as severe intraocular inflammation mimicking endophthalmitis. Delayed diagnosis and treatment are frequently reported. CASE PRESENTATION: A 43-year-old woman presented with 2-month blurred vision in her left eye. Ocular examination revealed hypopyon panuveitis. She was initially diagnosed with endogenous endophthalmitis, which proved irresponsive to antimicrobial therapy. High-dose prednisolone was given afterward, but this failed to stop the development and continuous progression of ocular inflammation. The diagnosis of ENKTL was finally confirmed from the pathological findings of oral ulcers and cervical lymph nodes and chemotherapy was prescribed. After the first cycle of chemotherapy, the patient's ocular inflammation subsided. Unfortunately, her left eye became phthisis with progressive visual loss within 9 months following the diagnosis. CONCLUSIONS: The diagnosis of intraocular ENKTL is frequently delayed, which can lead to severe problems for treatment as the disease is aggressive with a poor prognosis. It can be found not only in elderly patients but also in a middle-aged individual. In patients with ocular inflammation, a thorough systemic evaluation and histopathological examination of the associated systemic findings is extremely helpful and may reveal the cause of the ocular inflammation, including revealing possible ENKTL.

BILATERAL SEROUS RETINAL DETACHMENT AND UVEITIS ASSOCIATED WITH PEMBROLIZUMAB TREATMENT IN METASTATIC MELANOMA.

PURPOSE: To describe the pathological features, treatment, and resolution of pembrolizumab-associated retinal detachment. METHODS: A case report with a brief review of the literature and details of patient presentation, physical examination, systemic workup, fluorescein angiography, and indocyanine angiography. RESULTS: A 25-year-old white woman was diagnosed with unresectable metastatic melanoma of the skin with a BRAF V600E mutation. The patient was treated with pembrolizumab injections every 3 weeks, upon which quick remission was seen of the metastases. After five injections, visual acuity of the patient deteriorated to 20/32 in the right eye. Ocular examination revealed bilateral panuveitis, papillitis, and serous retinal detachments. Treatment consisted of an oral prednisone taper schedule, topical prednisolone drops, and cessation of the pembrolizumab therapy, after which complete resolution of the subretinal fluid was seen. CONCLUSION: Pembrolizumab therapy may cause the development of panuveitis, papillitis, and serous retinal detachment, symptoms which are able to be controlled with lengthy steroid therapy.

Granulomatous panuveitis associated with Hodgkin lymphoma: A case report with review of the literature.

BACKGROUND: Intraocular lymphoma (IOL) is an uncommon ophthalmic malignancy and poses a diagnostic challenge. Uveitis associated with systemic lymphoma (USL) has been predominantly attributed to non-Hodgkin lymphoma (NHL) and rarely reported with Hodgkin lymphoma (HL) in the literature. METHODS: Case report with review of the literature. RESULTS: A 25-year-old healthy male presented with bilateral granulomatous panuveitis including vasculitis and discrete chorioretinal yellowish-white lesions. Macular optical coherence tomography (OCT) of both eyes revealed a disruption of ellipsoid and interdigitation zones over the areas of subretinal lesions as well as a small sub-retinal pigment epithelium (RPE) deposit in one eye. Thorough uveitis workup revealed clavicular, axillary and cervical lymphadenopathy, and biopsy of lymph nodes confirmed the diagnosis of nodular lymphocyte-predominant (NLP) HL. Six months later and after receiving chemotherapy, all symptoms and most of clinical signs resolved. CONCLUSIONS: Clinical features of USL do not differ between HL and NHL. However, the age of presentation may be much younger in HL. Ocular manifestations can precede systemic HL diagnosis, as shown in our patient. Therefore, USL should be part of the differential diagnosis of panuveitis. Paraneoplastic inflammation is thought be the cause of uveitis associated with HL. The sub-RPE deposit and disruption of ellipsoid and interdigitation zones on OCT have not been documented before as a manifestation of uveitis secondary to HL. In addition, the NLP subtype of HL was reported in only 1 case with uveitis in the literature.

Ponatinib Inducing a Panuveitis with Choroidal Effusions and Neurosensory Retinal Detachment in a Patient with Chronic Myeloid Leukaemia.

CASE SUMMARY: We present the case of a 50 year old male patient being treated for chronic myeloid leukemia by the tyrosine kinase inhibitor, Ponatinib. After 3 months of treatment, he developed a sight-threatening granulomatous panuveitis in both eyes, with choroidal effusions and neurosensory retinal detachments. Except for a positive interferon-gamma release assay suggesting previous Tuberculosis exposure, all uveitis investigations were normal. Discontinuation of the suspected causative drug led to resolution of signs and a consequent improvement in visual acuity. CONCLUSION: Ponatinib use may be associated with with a uveitic phenotype that is reminiscent of Harada's disease. We compare and contrast this rare ocular phenomenon with Vogt-Koyanagi-Harada syndrome and discuss a possible immunological basis.

Long-term Management of Panuveitis and Choroidal Mass Associated with Rosai Dorfman Disease with Pegylated Interferon.

PURPOSE: To present a patient with Rosai-Dorfman Disease (RDD), a histiocytic proliferative disorder typified by lymphadenopathy with rare ocular manifestations, who developed panuveitis that responded to pegylated interferon. METHODS: Descriptive case report of a patient with RDD with multi-organ involvement including ocular manifestations including bilateral panuveitis with choroidal masses. RESULTS: A 54-year-old African American woman with known systemic RDD of the breast, lung, and gastrointestinal tract presented with panuveitis with choroidal masses in both eyes. Her systemic and ocular disease initially responded well to oral and topical steroid therapy. Later, however, her systemic disease progressed with multiple muscular and bony lesions. Systemic therapy was switched to pegylated interferon, a cytokine with antiviral, antitumor and immunomodulatory activity. After 14 months of therapy with pegylated interferon, the patient's systemic and ocular disease stabilized. CONCLUSION: Rosai-Dorfman disease may be complicated by panuveitis and choroidal masses that may respond to pegylated interferon with stabilization of systemic and ocular manifestations. A multi-disciplinary approach is essential given the unique diagnostic and management challenges of RDD.

Use of fluocinolone acetonide intravitreal implant to manage chronic panuveitis for long-term inflammatory control without interfering with systemic immunity.

We report 2 patients with chronic panuveitis who were treated with fluocinolone acetonide intravitreal implant (Yutiq, EyePoint Pharmaceuticals Inc, Watertown, MA) intended to control ocular inflammation long term without interfering with systemic immunity. The first case was a man in his 50s referred for ocular complaints in the setting of ongoing immunotherapy for the treatment of metastatic melanoma. He was diagnosed with bilateral drug-induced panuveitis. Treatment objectives were outlined as reduction of inflammation, prevention of uveitis recurrence, and continuation of systemic immunomodulatory therapy in order to maintain malignancy remission; the patient was treated with fluocinolone acetonide intravitreal implant bilaterally and at 18 months' follow-up had 20/20 bilateral visual acuity and no inflammation. In case 2, a woman in her 70s, presented with a 2-month history of worsening floaters and blurry vision. She was phakic, with bilateral nuclear sclerotic cataracts, 1+ vitreous cells and 2+ haze, diffuse vasculitis, and central leakage around the optic nerve and posterior pole. She was diagnosed with bilateral idiopathic panuveitis with retinal vasculitis. The patient continued to do well at 1 year following intravitreal implantation with fluocinolone acetonide.

Interferon-induced sarcoidosis with uveitis as the initial symptom: a case report and review of the literature.

BACKGROUND: In recent years, numerous studies have reported the development or exacerbation of sarcoidosis due to interferon therapy. However, ocular lesions rarely present as initial symptoms. Herein, we describe a rare case of interferon-α-induced sarcoidosis with uveitis as the initial symptom, and present a review of the relevant literature. CASE PRESENTATION: This case involved a 62-year-old-Japanese woman with a history of a combination treatment of pegylated interferon-α-2a, ribavirin, and simeprevir, after which she developed granulomatous panuveitis. She was subsequently diagnosed with sarcoidosis following histological examination of skin biopsy specimens. In addition to reporting this case, we performed a literature review of 27 cases (24 case reports) of histopathologically diagnosed interferon-α-induced sarcoidosis published between January 2009 and November 2018. CONCLUSIONS: Among the reviewed cases, 23 (85.1%) cases developed skin lesions and 19 (70.1%) had lung lesions. Only three cases (11.1%) had accompanying eye lesions. Interferon-α therapy was discontinued in 16 cases (52.9%), and the majority exhibited improvement after systemic corticosteroid treatment. There are few reported cases of interferon-α-induced sarcoidosis with uveitis as the initial symptom. However, if uveitis develops during or after interferon-α treatment, it might represent an initial symptom of interferon-α-induced sarcoidosis, as observed in the present case.

Panuveitis Presumed Secondary to Ibrutinib Therapy.

Although a small number of cases of secondary uveitis have been documented in the setting of ibrutinib therapy, panuveitis has not previously been described with this medication. The authors describe a presumed case of panuveitis in a patient on ibrutinib for chronic lymphocytic leukemia. The purpose of this report is to document a case of asymmetric, bilateral panuveitis in the setting of ibrutinib use. Panuveitis may develop in the setting of ibrutinib use, and local steroid therapy can be successfully used for treatment without cessation of systemic cancer therapy. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:160-164.].

Outcome of Intravitreal Dexamethasone Implant Use in Uveitic Eyes Undergoing Pars Plana Vitrectomy Surgery.

Purpose: To report the outcomes in eyes with noninfectious uveitis receiving dexamethasone implant at the time of pars plana vitrectomy (PPV).Methods: Retrospective analysis of visual acuity (VA), intraocular pressure (IOP), vitreous haze score (VHS), and central subfield thickness (CST) at baseline and follow-up visits.Results: Fourteen eyes received dexamethasone implant at the time of PPV. The CST was improved from 469 ± 182 µm at baseline to 320 ± 60 at 6 months (p = .0112) and 295 ± 46 at 12 months (p = .0728). Vitritis only recurred in 2 eyes at 6 months (18.2%) and 1 eye at 12 months (14.3%). The probability of VA improvement of ≥0.3 logMAR was 57% at 6 months and 66% at 12 months. Therapy for IOP rise was initiated in 6 eyes (42.9%).Conclusions: Local delivery of dexamethasone implant with PPV is a feasible method to counteract postoperative inflammation and macular thickening.

Panuveitis in patient on ipilimumab/nivolumab combination for small-cell lung cancer treated with an intravitreal dexamethasone implant.

BACKGROUND: Immunotherapy with checkpoint inhibitors has demonstrated durable responses and remarkable antitumor effects in a variety of cancers. Although these agents are generally well-tolerated, patients can experience immune-related adverse events (irAEs) that require prompt recognition by healthcare providers. Immune-related ocular toxicities are rare, but serious adverse events have been reported with the use of checkpoint inhibitors.Case presentation: Here, we describe a rare case of panuveitis during Nivolumab and Ipilimumab combination treatment in a patient being treated for recurrent Small Cell Lung Cancer (SCLC). The patient was managed with an injection of Ozurdex (Allergan, Madison, NJ), a dexamethasone intravitreal implant. The patient had a resolution of inflammation and an improvement in her vision and was able to resume nivolumab monotherapy without recurrence of the panuveitis. CONCLUSION: This case highlights the importance of early recognition of ocular irAEs by ocular oncologists and the successful approach to treatment of immunotherapy-induced panuveitis in order to avoid permanent cessation of therapy.

Panuveitis in Sweet syndrome.

Ocular manifestations of Sweet syndrome, or acute febrile neutrophilic dermatosis, are usually limited to the anterior segment. We report the case of a patient with bilateral panuveitis and retinal vasculitis associated with Sweet syndrome. A 45-year-old Asian female with an undiagnosed febrile illness with rash presented with bilateral panuveitis with haemorrhagic occlusive retinal vasculitis. Skin biopsy confirmed Sweet Syndrome. Intraocular inflammation resolved with a combination of topical and systemic corticosteroids as well as intravenous cyclophosphamide, with resulting permanent severe right visual impairment. Although an uncommon condition, Sweet syndrome should be considered in any febrile patient with skin lesions and uveitis.