Detection of Secondary Corneal Lactoferrin Amyloidosis Based on Histologic Biopsies Combined with Mass Spectrometry: A Case Report.

Amyloidosis is characterized by systemic or local deposition of amyloid fibrils outside organs and tissues. Amyloidosis is rarely seen on cornea. A 30-year-old woman patient had had trichiasis in both eyes for 8 years. Trichiasis was observed, which touched the cornea. Slit lamp microscopy showed white gelatinous droplet-like eminences and trichiasis in the lower cornea of the right eye. Optical coherence tomography showed that the lesion involved most of the cornea. Hematoxylin and eosin staining showed that most of the stroma stained red, with scattered inflammatory cells. High expression of lactoferrin was detected by mass spectrometry, and the case was diagnosed as secondary corneal lactoferrin amyloidosis in the right eye.

Scanning electron microscopy of panitumumab-induced eyelash and hair alterations - Pili canaliculi.

Panitumumab is a monoclonal antibody against the epidermal growth factor receptor used in metastatic colorectal cancer; in addition to tumor cells, it acts on epidermal keratinocytes and on the outer root sheath and presents skin toxicity in up to 90% of cases. A scanning electron microscope was used to examine the eyelashes and hairs of a 65-year-old patient with eyelash trichomegaly, curly hair, and paronychia undergoing treatment with panitumumab. Grooving in the hair shafts were identified, which were more evident in the eyelashes. Similar to oral epidermal growth factor inhibitors (erlotinib and gefitinib), panitumumab can cause acquired pili canaliculi.

Lymphedema distichiasis syndrome may be caused by FOXC2 promoter-enhancer dissociation and disruption of a topological associated domain.

Lymphedema distichiasis syndrome (LDS) is a rare autosomal dominant condition characterized by lower limb lymphedema, distichiasis, and variable additional features. LDS is usually caused by heterozygous sequence variants in the FOXC2 gene located at 16q24, but in one previous instance LDS has resulted from a balanced reciprocal translocation with a breakpoint at 16q24, 120 kb distal to the FOXC2 gene suggesting a position effect. Here, we describe a second family with LDS caused by a translocation involving 16q24. The family were ascertained after detection of a paternally inherited balanced reciprocal translocation t(16;22)(q24;q13.1) in a pregnancy complicated by severe fetal hydrops. There was a past history of multiple miscarriages in the father's family, and a personal and family history of lymphedema and distichiasis, consistent with the diagnosis of LDS. Using whole genome amplified DNA from single sperm of the male proband, bead array analysis demonstrated that the FOXC2 gene was intact and the chromosome 16 breakpoint mapped to the same region 120Kb distal to the FOXC2 gene. This case highlights the clinical consequences that can arise from a translocation of genomic material without dosage imbalance, and that it is increasingly feasible to predict and characterize possible effects with improved access to molecular techniques.

Prospective observational study of chemotherapy-induced alopecia after sequential FEC + taxane and the effects of age in breast cancer patients.

BACKGROUND: Chemotherapy-induced alopecia (CIA) is a common and quite distressing adverse effects of chemotherapy. There are few detailed observational studies of CIA or of the impact of age on CIA. We performed a prospective observational study to investigate the prevalence and degree of CIA, including CIA of eyebrows, eyelashes, and body, and we examined patient's recovery from CIA, focusing on age-depending effects. METHODS: We analyzed 68 female Japanese patients with breast cancer (median age 53 years, range 29-76 years) who received perioperative adjuvant chemotherapy with fluorouracil/epirubicin/cyclophosphamide (FEC) and taxane. A questionnaire was administered at the point of chemotherapy completion and 6 and 12 months after chemotherapy completion. RESULTS: CIA occurred in all patients, with severe hair loss irrespective of age. CIA occurred mainly in the scalp but also in the eyebrows, eyelashes, and body for most of the patients. There were significant associations between the patient's age and the onset of hair regrowth in the eyebrows, eyelashes, and body. The onset of eyebrows, eyelash, and body hair growth were significantly shorter in the premenopausal patients. Any hair changes (e.g., thinned diameter, softer texture, curlier structure) were reported by 85.3% of the patients. CONCLUSIONS: Severe CIA occurred in all 68 patients who received FEC and taxane chemotherapy. The present findings provide the first data demonstrating that age was not associated with the degree or incidence of hair loss, but age affected the recovery from CIA. These results contribute more accurate information provision and insights regarding the proper treatment of CIA.

[Genetic analysis and clinical phenotype of a family with lymphedema-distichiasis syndrome].

OBJECTIVE: To identify the genetic causes of a family with lymphedema-distichiasis syndrome (LDS). METHODS: The whole exome sequencing was performed in a aborted fetus as the proband, and a candidate gene was identified. Peripheral blood of 8 family members were collected. Genotypic-phenotypic analysis were carried out through PCR amplification and Sanger sequencing. RESULTS: The proband, and the mother, grandmother, uncle, granduncle of the proband all had distichiasis or varix of lower limb carried a FOXC2:c.595dupC frame shift mutation, and other subjects without any significant phenotypes did not present the mutation. CONCLUSIONS: The FOXC2:c.595dupC frame shift mutation is the genetic cause of this family, which can lead to autosomal dominantly LDS, presenting nuchal translucency thickening and hydrops fetal during pregnancy, and the prognosis is usually good.

[Demodex and ocular surface disease]. / Demodex et pathologies de la surface oculaire.

Demodex is a saprophytic mite of the ocular adnexa, which can in certain circumstances proliferate on the skin of the face and on the eyelid margins. It is involved in facial rosacea (especially in the papulopustular form) and in the development or aggravation of anterior and/or posterior blepharitis or even keratoconjunctivitis, often in association with cutaneous lesions ; the pathophysiology is often multifactorial. Symptoms are non-specific, but the presence of cylindrical sleeves on the eyelashes is very suggestive of infestation, and certain techniques of biomicroscopic examination or imaging, such as confocal microscopy in vivo, allow direct visualization of the parasite. Parasitological examination of the eyelashes can confirm the diagnosis and can be improved by good sampling technique. Eyelid hygiene and oil-based ointments are the cornerstone of treatment. New specific treatments, in particular topical treatments based on tea tree oil, ivermectin, as well as pulsed light therapy and micro-exfoliation of the eyelid margin, can help to reduce the parasitic load and improve symptoms.

Ocular Demodex: a systematic review of the clinical literature.

PURPOSE: There is increasing clinical and research interest in the potential contribution of Demodex to ocular surface disease. The aim of this systematic review was to summarise and synthesise current clinical evidence relating to the aetiology, diagnosis and treatment of ocular Demodex. RECENT FINDINGS: A comprehensive literature search was performed in OVID Medline, OVID Embase, and clinical trial registries, for studies published between 1990 and August 2019, examining Demodex on the ocular surface. The review included primary clinical research studies and systematic reviews of primary clinical research studies, where Demodex was considered in the context of the ocular surface and/or adnexa. Studies were categorised using the National Health and Medical Research Council evidence hierarchy. Risk of bias assessment was performed using validated tools for studies categorised as providing Level I or II evidence. A total of 87 studies were eligible for inclusion, including two systematic reviews. Most studies (60%) were observational, describing the prevalence of ocular Demodex in different clinical populations. There was a high degree of variability in the epidemiological data derived from cross-sectional aetiology studies. There was mostly consistent evidence to support an association between ocular Demodex and chronic blepharitis. Seven diagnostic test-accuracy studies were identified, which considered a range of techniques, including slit lamp examination for cylindrical eyelash collarettes and/or eyelash manipulation techniques, light microscopic evaluation of epilated eyelashes and in vivo confocal microscopy. There is currently no accepted gold-standard diagnostic method for ocular Demodex. For intervention studies, there was one systematic review, 11 published randomised trials, six trial registry entries, and nine case series. Despite a number of recent trials, the appropriate treatment regimen for ocular Demodex (including the optimal criteria and timing of an intervention) is not clearly established. CONCLUSIONS: This comprehensive narrative synthesis has captured the landscape of clinical evidence relating to the prevalence, aetiology, diagnosis and treatment of ocular Demodex. There remain opportunities to enhance understanding of its role in ocular surface disease, best diagnostic approaches and optimal treatment protocols.

FOXC2 Disease Mutations Identified in Lymphedema Distichiasis Patients Impair Transcriptional Activity and Cell Proliferation.

FOXC2 is a member of the human forkhead-box gene family and encodes a regulatory transcription factor. Mutations in FOXC2 have been associated with lymphedema distichiasis (LD), an autosomal dominant disorder that primarily affects the limbs. Most patients also show extra eyelashes, a condition known as distichiasis. We previously reported genetic and clinical findings in six unrelated families with LD. Half the patients showed missense mutations, two carried frameshift mutations and a stop mutation was identified in a last patient. Here we analyzed the subcellular localization and transactivation activity of the mutant proteins, showing that all but one (p.Y109*) localized to the nucleus. A significant reduction of transactivation activity was observed in four mutants (p.L80F, p.H199Pfs*264, p.I213Tfs*18, p.Y109*) compared with wild type FOXC2 protein, while only a partial loss of function was associated with p.V228M. The mutant p.I213V showed a very slight increase of transactivation activity. Finally, immunofluorescence analysis revealed that some mutants were sequestered into nuclear aggregates and caused a reduction of cell viability. This study offers new insights into the effect of FOXC2 mutations on protein function and shows the involvement of aberrant aggregation of FOXC2 proteins in cell death.

Genetic analysis and clinical phenotype of a family with lymphedema-distichiasis syndrome / 浙江大学学报·医学版

OBJECTIVE@#To identify the genetic causes of a family with lymphedema-distichiasis syndrome (LDS).@*METHODS@#The whole exome sequencing was performed in a aborted fetus as the proband, and a candidate gene was identified. Peripheral blood of 8 family members were collected. Genotypic-phenotypic analysis were carried out through PCR amplification and Sanger sequencing.@*RESULTS@#The proband, and the mother, grandmother, uncle, granduncle of the proband all had distichiasis or varix of lower limb carried a @*CONCLUSIONS@#The

Bilateral upper and lower eyelid margin swelling and madarosis due to lymphoma.

Over a 2-year period, swellings of all 4 eyelid margins developed in a 32-year-old woman and was accompanied by complete loss of eyelashes. An inflammatory dermatologic condition was considered the most likely cause. A full-thickness right lower eyelid biopsy revealed a multinodular lymphoid tumor at the eyelid margin which immunophenotypically and genetically was diagnosed as an extranodal marginal zone lymphoma. The mode of presentation of the disease was considered to be most unusual, as was its B cell lineage, since the majority of primary cutaneous lymphomas are of T-cell origin. Systemic workup demonstrated bilateral involvement of the external auditory canals.

The association of keratoconus with blepharitis.

BACKGROUND: Identifying potentially treatable risk factors for the progression of keratoconus is of great importance. The purpose of this study was to determine the association between blepharitis and keratoconus. METHODS: In this prospective, comparative, observational study, 50 keratoconus participants from the central district of the Clalit Health Services Health Maintenance Organization in Israel underwent comprehensive eye examination. Seventy-two healthy medical personnel of similar ages were randomly chosen as a control group. The signs and symptoms of blepharitis in each participant were assessed. A thorough survey of the eyelids (scales and foam on the eyelashes, missing eyelashes and expression of meibomian gland contents) was performed. All participants were required to complete two questionnaires: the Ocular Surface Disease Index questionnaire and a questionnaire regarding symptoms, signs and risk factors for blepharitis. RESULTS: Blepharitis was more common in keratoconus participants than in the control group (24 per cent versus 2.8 per cent, p < 0.001). A higher proportion of keratoconus participants reported rubbing their eyes more than once a day (36 per cent versus 11.1 per cent, p = 0.002) as well as red and tired eyes (12 per cent versus zero per cent, p = 0.009). On external eye examination, signs of blepharitis and meibomian gland dysfunction were found more frequently in the keratoconus group (p < 0.05). CONCLUSIONS: Signs and symptoms of blepharitis occur more often in keratoconus participants than in healthy individuals. Blepharitis-related inflammation and associated eye rubbing may contribute to disease progression.

[Vitiligo occurring on dermal melanocytosis (nevus of Ota) in a dark-skinned patient]. / Vitiligo dévéloppé sur une mélanocytose dermique (nævus de Ota) chez une patiente à peau foncée.

BACKGROUND: Nevus of Ota is a rare disease most frequently found in Asians. It presents clinically as a bluish gray hyperpigmentation of one side of the face. Transformation into melanoma and glaucoma are the main risks. The appearance of vitiligo lesions with poliosis within a nevus of Ota is exceptional. PATIENTS AND METHODS: A 22-year-old female patient with a nevus of Ota consulted for depigmentation of the eyelashes. Physical examination revealed hyperpigmentation in the right orbitofrontal part of her face, achromic macules and eyelash poliosis. A diagnosis was made of vitiligo developing on a nevus of Ota. Ophthalmologic examination showed hyperpigmentation of the sclera. Regular dermatologic and ophthalmologic follow-up was instituted. DISCUSSION: Vitiligo is a condition characterized by the development of depigmented lesions secondary to chronic degradation of the melanocytes of the epidermis and the follicles. Its occurrence on congenital nevus and melanoma has already been reported. However, its appearance in dermal melanocytosis is very rare. Since the first observation of this association in 1979, only 4 other cases have been reported. The pathogenic mechanisms of this association are still poorly understood. Histopathological examination generally shows a loss of epidermal melanocytes, especially in the basal layer, while dermal melanocytes remain unaffected. In this context, vitiligo developed on dermal melanosis appears to result from the difference between the properties of normal (epidermal) melanocytes and ectopic (dermal) melanocytes. CONCLUSION: Association of vitiligo with nevus of Ota is rare. Herein, we report a new case in a dark-skinned subject.