Severe Hair Loss of the Scalp due to a Hair Dye Containing Para phenylenediamine

We report the case of a 41-year-old female showing severe hair loss approximately 90% after the use of a hair dye. These symptoms developed six days after the use of a hair dye containing PPD. A patch test showed a (++) reaction at 48 h to 1% PPD in petrolatum, whereas all metals and white petrolatum were negative. She was therefore diagnosed with contact dermatitis due to PPD, resulting in hair loss. The skin lesions gradually improved after starting treatment with the systemic corticosteroids. The possibility that allergic contact dermatitis from hair dyes may be responsible for telogen effluvium should always be considered in a patient with increased hair loss

高齢で発症した重症筋無力症は重症化しやすい

Objective: The continuous increase in the number of patients presenting with late-onset myasthenia gravis (LOMG) underscores the need for a better understanding of the clinical course and the establishment of an optimal therapeutic strategy. We aimed to clarify factors associated with clinical outcomes in LOMG. Methods: We retrospectively reviewed the clinical profiles of 40 patients with early-onset MG (EOMG) (onset age: 49 years or younger), 30 patients with non-elderly LOMG (onset age: 50–64 years), and 28 patients with elderly LOMG(onset age: 65 years or older) and compared the subgroups according to onset age and thymus status. The evaluated parameters were MGFA classification before treatment, MG-ADL score, complicating diseases, antibody titer, treatment, and MGFA post-intervention status. Results: Elderly LOMG patients showed transition to generalized symptoms at a higher frequency and underwent thymectomyless frequently than EOMG and non-elderly LOMG patients (p < 0.001). The frequencies of crisis and plasmapheresis were significantly lower in thymectomized LOMG patients without thymoma than in thymectomized LOMG patients with thymoma or non-thymectomized LOMG patients (p < 0.01, P < 0.05, respectively). However, the outcome was not significantly different. All of the thymectomized LOMG patients without thymoma presenting with hyperplasia or thymic cyst had a favorable clinical course. Conclusions: Our study showed that elderly LOMG patients are more prone to severity, suggesting that they require aggressive immunomodulatory therapy

Corneal Fibroblasts as Sentinel Cells and Local Immune Modulators in Infectious Keratitis

The cornea serves as a barrier to protect the eye against external insults including microbial pathogens and antigens. Bacterial infection of the cornea often results in corneal melting and scarring that can lead to severe visual impairment. Not only live bacteria but also their components such as lipopolysaccharide (LPS) of Gram-negative bacteria contribute to the development of inflammation and subsequent corneal damage in infectious keratitis. We describe the important role played by corneal stromal fibroblasts (activated keratocytes) as sentinel cells, immune modulators, and effector cells in infectious keratitis. Corneal fibroblasts sense bacterial infection through Toll-like receptor (TLR)–mediated detection of a complex of LPS with soluble cluster of differentiation 14 (CD14) and LPS binding protein present in tear fluid. The cells then initiate innate immune responses including the expression of chemokines and adhesion molecules that promote the recruitment of inflammatory cells necessary for elimination of the infecting bacteria. Infiltrated neutrophils are activated by corneal stromal collagen and release mediators that stimulate the production of pro–matrix metalloproteinases by corneal fibroblasts. Elastase produced by Pseudomonas aeruginosa (P. aeruginosa) activates these released metalloproteinases, resulting in the degradation of stromal collagen. The modulation of corneal fibroblast activation and of the interaction of these cells with inflammatory cells and bacteria is thus important to minimize corneal scarring during treatment of infectious keratitis. Pharmacological agents that are able to restrain such activities of corneal fibroblasts without allowing bacterial growth represent a potential novel treatment option for prevention of excessive scarring and tissue destruction in the cornea

Aqueous-Deficient Dry Eye Exacerbates Signs and Symptoms of Allergic Conjunctivitis in Mice

Dry eye disease (DED) and allergic conjunctivitis affect a large number of patients, and many patients usually have both symptoms. We investigated the interactions between DED and allergic conjunctivitis in mice. Four experimental groups were compared: control, DED, allergy, and allergy with DED. DED was induced by removing the extraorbital lacrimal glands of the mice. Allergic conjunctivitis was induced by intraperitoneal administration of ovalbumin and antigen eye drops. The early phase reaction of the allergy was evaluated using the clinical score, scratching behavior, and vascular permeability in the conjunctiva. Epithelial barrier function was assessed by an LC-biotin assay. Tear fluid volume and corneal fluorescein staining decreased in the DED and allergy with DED groups. LC-biotin penetrated the entire epithelium of both the cornea and conjunctiva in DED mice. The clinical score of the early phase reaction was higher in allergy-induced mice than in non-allergy mice. Edema of the eyelid and conjunctiva were aggravated in mice with DED. The number of scratching episodes and leakage of Evans blue into the conjunctiva were higher in allergy-induced DED mice than in control mice. The presence of aqueous-deficient dry eye caused ocular surface epithelial damage and exacerbated allergic signs and symptoms

Depletion of Thymus-Derived CD4+CD25+ T Cells Abrogates the Suppressive Effects of α-galactosylceramide Treatment on Experimental Allergic Conjunctivitis

Background: We showed previously that α-galactosylceramide (α-GalCer) treatment elevated splenic CD4+ CD25+Foxp3+ T-cell numbers and suppressed the development of experimental allergic conjunctivitis (EC). Here, we investigated whether CD4+CD25+Foxp3+ T cells mediate the suppressive effects of α-GalCer treatment on EC. Methods: To deplete CD4+CD25+Foxp3+ T cells, neonatal mice were thymectomized and intraperitoneally injected with anti-CD25 Ab. At 6 weeks of age, these mice were immunized with ragweed (RW) in aluminum hydroxide. Ten days later, the mice were challenged with RW in eye drops and 24 hours later, the conjunctivas and spleens were harvested for histological and flow cytometric analyses, respectively. α-GalCer or vehicle was injected 2 hours prior to RW challenge. In addition, α-GalCer was injected into thymus-intact EC-developing mice that had not been treated with anti-CD25 Ab. Results: α-GalCer treatment significantly suppressed EC in the thymus-intact mice that had not been treated with anti-CD25 Ab. In contrast, α-GalCer treatment of thymectomized and anti-CD25 Ab-treated mice did not affect the severity of EC or splenic CD4+CD25+Foxp3+ T-cell numbers. However, α-GalCer treatment did significantly increase splenic CD4+CD25+Foxp3+ T-cell numbers in thymectomized mice that had not received anti-CD25 Ab. Conclusions: α-GalCer treatment during the effector phase of EC increased CD4+CD25+Foxp3+ T-cell numbers, which in turn suppressed the development of EC

Efficacy of oral immunotherapy with a rice-based edible vaccine containing hypoallergenic Japanese cedar pollen allergens for treatment of established allergic conjunctivitis in mice

Background: We have previously shown that prophylactic oral administration of transgenic rice seeds expressing hypoallergenic modified antigens suppressed the development of allergic conjunctivitis induced by Japanese cedar pollen. We have now investigated the efficacy of oral immunotherapy with such transgenic rice for established allergic conjunctivitis in mice. Methods: BALB/c mice were sensitized with two intraperitoneal injections of Japanese cedar pollen in alum, challenged with pollen in eyedrops, and then fed for 16 days with transgenic rice seeds expressing modified Japanese cedar pollen allergens Cry j 1 and Cry j 2 or with nontransgenic rice seeds as a control. They were then challenged twice with pollen in eyedrops, with clinical signs being evaluated at 15 min after the first challenge and the eyes, blood, spleen, and lymph nodes being isolated at 24 h after the second challenge. Results: The number of eosinophils in the conjunctiva and the clinical score for conjunctivitis were both significantly lower in mice fed the transgenic rice than in those fed nontransgenic rice. Oral vaccination with transgenic rice seeds also resulted in a significant increase in the production of IFN-γ by splenocytes, whereas it had no effect on the number of CD4+CD25+Foxp3+ regulatory T cells in the spleen or submandibular or mesenteric lymph nodes. Conclusions: Oral administration of transgenic rice seeds expressing hypoallergenic allergens ameliorated allergic conjunctivitis in the established setting. Such a rice-based edible vaccine is potentially both safe and effective for oral immunotherapy in individuals with allergic conjunctivitis

Role of Damage-Associated Molecular Patterns (DAMPs/Alarmins) in Severe Ocular Allergic Diseases

Severe ocular allergic diseases, such as atopic keratoconjunctivitis and vernal keratoconjunctivitis, cause severe allergic inflammation in the conjunctiva and corneal epithelial damage, resulting in visual disturbances. The involvement of damage (danger)-associated molecular patterns (DAMPs/alarmins) in the pathogenesis of these diseases has been recognized. Alarmins released from damaged corneal epithelial cells or eosinophils play a critical role in the induction of corneal lesions, vicious loop of corneal injury, and exacerbation of conjunctival allergic inflammation. Alarmins in the conjunctiva also play an essential role in the development of both allergic inflammation, based on the acquired immune system, and type 2 inflammation by innate immune responses in the ocular surface. Therefore, alarmins may be a potentially important therapeutic target in severe refractory ocular allergic diseases