An unusual presentation of thymoma: dysgeusia, ulcerative colitis, keratoconjunctivitis sicca, autoimmune retinopathy and myasthenia gravis

A 41-year-old female presented with dysgeusia, dry eyes, nyctalopia with progressive visual field constriction (due to autoimmune retinopathy) and gastrointestinal symptoms (due to ulcerative colitis). She was subsequently admitted to intensive care with a myasthenic crisis, and CT of the thorax demonstrated a thymoma.Following thymectomy and adjuvant radiotherapy, she has remained in complete remission from her ulcerative colitis and myasthenia gravis, her retinopathy has stabilised and there has been no thymoma recurrence over a 10-year postoperative period. There was a brief relapse of her dysgeusia (causing weight loss) and dry eye symptoms 3 years after her surgery, which resolved 8 months later. While the association of thymomas with paraneoplastic syndromes (PNS) is well established, it is unusual to present with multiple PNS, and some of these have only been documented in sparse case reports to date. Thymectomy played a crucial role in improvement and stabilisation of her PNS.

Systemic Treatment of Immune-Mediated Keratoconjunctivitis Sicca with Allogeneic Stem Cells Improves the Schirmer Tear Test Score in a Canine Spontaneous Model of Disease

Keratoconjunctivitis sicca (KCS) is characterized by ocular discomfort, conjunctival hyperaemia, and corneal scarring, causing reduced aqueous tear production that can be measured using the standard Schirmer tear test (STT). Canine adipose tissue-derived MSCs (cATMSCs) have been proposed as treatment due to their anti-inflammatory effect, by releasing cytokines and immunomodulatory soluble factors. Purpose: The aim of this study was to evaluate the effect of the systemic administration of cATMSCs on tear production in dogs with immune-mediated KCS, compared to classical Cyclosporine A (CsA) treatment. Methods: Twenty-eight client-owned dogs with spontaneous KCS were allocated in the experimental group (n = 14, treated with systemic cATMSCs or control group (n = 14, treated with CsA). SST values increased significantly at days 15 (p = 0.002), 45 (p = 0.042) and 180 (p = 0.005) with no observed side-effects in the experimental group. Eyes with an initial STT value of 11–14 mm/min maintained significant improvement at day 180, needing only artificial tears as treatment. Eyes with an initial STT value <11 mm/min needed cyclosporin treatment at day 45, so follow-up was stopped. Control animals treated with CsA did not improve their STT at day 180. Results and Conclusions: Systemic allogeneic cATMSCs application appeared to be a feasible and effective therapy with positive outcome in dogs with initial STT between 11–14 mm/min, with a significant improvement in tear production. The STT increment was maintained for at least 180 days, without needing additional medication, thus suggesting it could constitute an alternative therapy to classical immunosuppressive treatments.

Genes of Congenital Dermatologic Disorders in Dogs—A Review

This article presents an overview of up-to-date identified genes responsible for congenital canine skin diseases of dogs and the characteristics of these diseases. Congenital skin diseases constitute a specific group of dermatologic disorders that plays an important role in breeding of purebred dogs. They include primary seborrhoea, ichthyosis, hereditary nasal parakeratosis, dermatomyositis, colour dilution alopecia, skin mucinosis, dermoid sinus, lethal acrodermatitis, acral mutilation syndrome, keratoconjunctivitis sicca, ichthyosiform dermatosis, bullous epidermolysis, exfoliative dermal lupus erythematosus, congenital footpad hyperkeratosis and sebaceous adenitis. In the majority of cases, their occurrence is linked to particular breeds. In more than half of these diseases a specific defective gene variant responsible for the disease has been identified. Genetic tests for identification of the relevant defective genes serve as an important tool in the diagnostics of diseases in veterinary practice and in breeding of purebred dogs.

Oral mucosa transplantation may improve tear film osmolarity in dogs with keratoconjunctivitis sicca - a preliminary study

ABSTRACT The objective of this study was to evaluate the use of cyclosporine 1% alone or associated with oral mucosa transplantation (OMT) in dogs with dry keratoconjunctivitis (KCS). Schirmer Tear Test (STT-1) and Tear Film Osmolarity (TFO) were measured in both eyes of 30 adult dogs (before and 45 days after treatment. The animals were divided into three groups (10 dogs for group): control (normal dogs), group I (GI, treated with 1% cyclosporine alone), and group II (GII, treated with 1% cyclosporine and OMT). All STT-1 and TFO values were subjected to the Shapiro-Wilk normality test, and all were normally distributed. STT-1 and TFO values before and after treatment were subjected to the T-Student Test. The STT‐1 and TFO values of the right eye were subjected to Repeated Measures ANOVA followed by a Tukey Test for comparison between groups I and II. Means with a value of p≤0.05 were considered significant. There was a decreased osmolarity in both groups after treatment. Mean osmolarity in GII (322.60±16.56 mOsm/L) was significantly lower than GI (336.40±5.66 mOsm/L). The OMT associated with cyclosporine 1% improved the osmolarity of the tear film in dogs with KCS with a seeming synergism between the clinical and surgical treatments.

Ophthalmic disorders in a referral population of seven breeds of brachycephalic dogs: 970 cases (2008–2017)

OBJECTIVE To evaluate the frequency of ophthalmic disorders in 7 brachycephalic dog breeds referred to an academic veterinary ophthalmology service. ANIMALS 970 client-owned dogs of 7 brachycephalic breeds that were evaluated by the ophthalmology service in a veterinary teaching hospital from January 2008 through December 2017. PROCEDURES Medical records of 7 brachycephalic breeds (ie, Boston Terriers, English Bulldogs, French Bulldogs, Lhasa Apsos, Pekingese, Pugs, and Shih Tzus) were reviewed to collect data regarding patient signalment, ophthalmic diagnoses, affected eyes, and number and dates of visits. RESULTS Median age at the first examination was 7 years (range, 23 days to 22 years). The number of dogs seen for a first examination increased with age. Corneal ulcers, keratoconjunctivitis sicca, corneal pigmentation, immature cataracts, and uveitis were each diagnosed in ≥ 100 dogs and represented 40.4% (1,161/2,873) of all diagnoses. On the basis of anatomic location, 66.3% (1,905/2,873) of all disorders were located in either the cornea (1,014/2,873 [35.2%]) or adnexa (891/2,873 [31%]). There was a significant difference in breed proportion in the study population; of the 7 breeds studied, Shih Tzus (34.3% [333/970]), Pugs (20.8% [202/970]), and Boston Terriers (16.6% [161/970]) were the most prevalent breeds. The frequency of some diseases within the referral population was associated with breed. CONCLUSIONS AND CLINICAL RELEVANCE Findings suggested that the most prevalent disorders for the brachycephalic breeds in this ophthalmic referral population were corneal ulcers, keratoconjunctivitis sicca, corneal pigmentation, immature cataracts, and uveitis. Although all dogs shared brachycephalic features, the frequency of specific ophthalmic diseases varied between breeds.

Natural and iatrogenic ocular manifestations of rheumatoid arthritis: a systematic review

Purpose To provide an overview of the ocular features of rheumatoid arthritis (RA) and of the ophthalmic adverse drug reactions (ADRs) that may be associated with the administration of antirheumatic drugs. Methods A systematic literature search was performed using the PubMed, MEDLINE, and EMBASE databases. In addition, a cohort of 489 RA patients who attended the Authors’ departments were examined. Results Keratoconjunctivitis sicca, episcleritis, scleritis, peripheral ulcerative keratitis (PUK), and anterior uveitis were diagnosed in 29%, 6%, 5%, 2%, and 10%, respectively, of the mentioned cohort. Ocular ADRs to non-steroidal anti-inflammatory drugs are rarely reported and include subconjunctival hemorrhages and hemorrhagic retinopathy. In patients taking indomethacin, whorl-like corneal deposits and pigmentary retinopathy have been observed. Glucocorticoids are frequently responsible for posterior subcapsular cataracts and open-angle glaucoma. Methotrexate, the prototype of disease-modifying antirheumatic drugs (DMARDs), has been associated with the onset of ischemic optic neuropathy, retinal cotton-wool spots, and orbital non-Hodgkin’s lymphoma. Mild cystoid macular edema and punctate keratitis in patients treated with leflunomide have been occasionally reported. The most frequently occurring ADR of hydroxychloroquine is vortex keratopathy, which may progress to “bull’s eye” maculopathy. Patients taking tofacitinib, a synthetic DMARD, more frequently suffer herpes zoster virus (HZV) reactivation, including ophthalmic HZ. Tumor necrosis factor inhibitors have been associated with the paradoxical onset or recurrence of uveitis or sarcoidosis, as well as optic neuritis, demyelinating optic neuropathy, chiasmopathy, and oculomotor palsy. Recurrent episodes of PUK, multiple cotton-wool spots, and retinal hemorrhages have occasionally been reported in patients given tocilizumab, that may also be associated with HZV reactivation, possibly involving the eye. Finally, rituximab, an anti-CD20 monoclonal antibody, has rarely been associated with necrotizing scleritis, macular edema, and visual impairment. Conclusion The level of evidence for most of the drug reactions described herein is restricted to the “likely” or “possible” rather than to the “certain” category. However, the lack of biomarkers indicative of the potential risk of ocular ADRs hinders their prevention and emphasizes the need for an accurate risk vs. benefit assessment of these therapies for each patient.

Increased Indoleamine 2,3-Dioxygenase Levels at the Onset of Sjögren’s Syndrome in SATB1-Conditional Knockout Mice

Sjögren’s syndrome (SS) is a chronic autoimmune disease characterized by dysfunction of salivary and lacrimal glands, resulting in xerostomia (dry mouth) and keratoconjunctivitis sicca (dry eyes). Autoantibodies, such as anti-SSA and anti-SSB antibodies, are hallmarks and important diagnostic factors for SS. In our previous study, we demonstrated that SS-like xerostomia was observed in SATB1 conditional knockout (SATB1cKO) mice, in which the floxed SATB1 gene was specifically deleted in hematopoietic cells as early as 4 weeks of age. In these mice, autoantibodies were not detected until 8 weeks of age in SATB1cKO mice, although exocrine gland function reached its lowest at this age. Therefore, other markers may be necessary for the diagnosis of SS in the early phase. Here, we found that mRNA expression of the interferonγ (IFN-γ) gene and the IFN-responsive indoleamine 2,3-dioxygenase (IDO) gene is upregulated in the salivary glands of SATB1cKO mice after 3 and 4 weeks of age, respectively. We detected l-kynurenine (l-KYN), an intermediate of l-tryptophan (l-Trp) metabolism mediated by IDO, in the serum of SATB1cKO mice after 4 weeks of age. In addition, the upregulation of IDO expression was significantly suppressed by the administration of IFN-γ neutralizing antibodies in SATB1cKO mice. These results suggest that the induction of IFN-dependent IDO expression is an initial event that occurs immediately after the onset of SS in SATB1cKO mice. These results also imply that serum l-KYN could be used as a marker for SS diagnosis in the early phases of the disease before autoantibodies are detectable.

Transplantation of limbal derived MSCs grown on contact lenses in dogs with dry eye syndrome - can stem cells help?

Keratoconjunctivitis Sicca (KCS), also known as “dry eye syndrome”, is a common ocular disease in dogs, caused by inflammation of the lacrimal gland, resulting in decreased tear production. Efforts are being made to develop alternative therapies in order to prevent lifelong use of drugs for patients with KCS. Mesenchymal stem cells (MSCs) are known to be effective in the treatment of many immune-mediated diseases in human and animal models due to their immunoregulatory properties. The aim of this study was to transplant limbal mesenchymal stem cells (LMSCs) to the ocular surface on contact lenses and to evaluate the therapeutic effects of the LMSCs by clinical examination findings. The animals were randomly divided into study and control groups. The LMSC group (n = 10) received LMSCs (at least 2×106 cells) cultured on contact lenses. The conventional treatment group (n = 10) received artificial tears, topical 0.05% Cs A, and antibiotic eye drops, 3 times a day for 4 weeks. The Schirmer test, tear break-up time, impression cytology, Rose Bengal staining, and tear osmolarity were measured in all patients. The findings of the pre-treatment, two weeks and four weeks after the treatment, were evaluated statistically. In both groups, significant improvement was present compared to the pre-treatment findings. However, there was no significant difference between the groups. KCS treatment using LMSCs produced on contact lenses is promising, with its ease of application, non-immunogenic properties and single dose administration.