Biallelic splicing variants in the nucleolar 60S assembly factor RBM28 cause the ribosomopathy ANE syndrome.

Alopecia, neurologic defects, and endocrinopathy (ANE) syndrome is a rare ribosomopathy known to be caused by a p.(Leu351Pro) variant in the essential, conserved, nucleolar large ribosomal subunit (60S) assembly factor RBM28. We report the second family of ANE syndrome to date and a female pediatric ANE syndrome patient. The patient presented with alopecia, craniofacial malformations, hypoplastic pituitary, and hair and skin abnormalities. Unlike the previously reported patients with the p.(Leu351Pro) RBM28 variant, this ANE syndrome patient possesses biallelic precursor messenger RNA (pre-mRNA) splicing variants at the 5' splice sites of exon 5 (ΔE5) and exon 8 (ΔE8) of RBM28 (NM_018077.2:c.[541+1_541+2delinsA]; [946G > T]). In silico analyses and minigene splicing experiments in cells indicate that each splice variant specifically causes skipping of its respective mutant exon. Because the ΔE5 variant results in an in-frame 31 amino acid deletion (p.(Asp150_Lys180del)) in RBM28 while the ΔE8 variant leads to a premature stop codon in exon 9, we predicted that the ΔE5 variant would produce partially functional RBM28 but the ΔE8 variant would not produce functional protein. Using a yeast model, we demonstrate that the ΔE5 variant does indeed lead to reduced overall growth and large subunit ribosomal RNA (rRNA) production and pre-rRNA processing. In contrast, the ΔE8 variant is comparably null, implying that the partially functional ΔE5 RBM28 protein enables survival but precludes correct development. This discovery further defines the underlying molecular pathology of ANE syndrome to include genetic variants that cause aberrant splicing in RBM28 pre-mRNA and highlights the centrality of nucleolar processes in human genetic disease.

Successful treatment with ustekinumab in CARD14-associated papulosquamous eruption in a Brazilian child.

CARD14-associated papulosquamous eruption (CAPE) was proposed in 2018 to describe the clinical features of psoriasis and pityriasis rubra pilaris with CARD 14 mutations. We report a 5-month-old female infant who developed CAPE-associated erythroderma. Although she did not respond to conventional therapies, she responded well to ustekinumab treatment at the age of 4 years.

"Angular" plasma cell cheilitis.

Plasma cell cheilitis is an extremely rare disease, characterized by erythematous-violaceous, ulcerated and asymptomatic plaques, which evolve slowly. The histological characteristics include dermal infiltrate composed of mature plasmocytes. We report a case of Plasma cell angular cheilitis in a 58-year-old male, localized in the lateral oral commissure.

Selenium compounds prevent amyloid ß-peptide neurotoxicity in rat primary hippocampal neurons.

Neuropathological hallmarks of Alzheimer's disease (AD) include amyloid plaque formation, neurofibrillary tangles, neuronal and synaptic loss. This study aims to identify the neuroprotective effects of the selenium compounds on the neurotoxicity of amyloid ß(1-42) in primary cultures of murine hippocampal neurons. Samples were subjected to immunocytochemistry and western blotting techniques to determine the role of treatments on neuronal viability and synaptic protein SNAP-25. We observed a reduced cell viability amyloid ß-peptide (1-42)-induced. When cells were co-treated with amyloid ß-peptide (1-42) and selenium compounds, we verified a strong increase in relative cell viability and in the level of synaptic marker synaptosomal-associated protein SNAP-25 induced by selenium compounds.

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.

Transmission electron microscopy of pili annulati.

BACKGROUND: Little is known about the ultrastructure of pili annulati. OBJECTIVES: To examine with transmission electron microscopy affected hairs of a family, whose diagnosis had been confirmed in five individuals with scanning electron microscopy, which showed surface undulations with "curtain-like" folding of the hair cuticula and to compare the findings with normal control. METHODS: Hairs of two affected patients and one control were embedded in resin and cut lengthwise to produce ultra-thin sections. RESULTS: The normal hair showed a parallel arrangement of dark lines associated with less electron-dense wide bands. Small cavities could be observed, mostly in the dark lines, affected hairs had a large number of cavities, associated or not with the insertion of melanosomes and loss of parallelism of the dark lines. Higher magnification showed a significant loss of this parallelism, resembling "wood grooves". Widened dark lines were observed in some areas. STUDY LIMITATIONS: Only a few hairs were examined. CONCLUSIONS: The present results suggest that the microcanaliculi of the hair surface, easily found with scanning electron microscopy, may be secondary not only to the cavities seen in the sections but also to the disorder of proteins that form this region, demonstrated by the changes of the cortex dark lines.

McCune-Albright syndrome - A case report with transmission electron microscopy.

McCune - Albright syndrome is a genetic disease with cutaneous mosaicism caused by post-zygotic activating mutations in GNAS locus, it has a triad of fibrous bone dysplasia, café-au-lait macules and precocious puberty. We examined a 22-year-old female patient with café au lait spot in right side of the abdomen, with a chessboard - like distribution, extending to right thigh with geographical contours, she has also an ovarian cyst, scoliosis and truncal obesity. Biopsies were taken from the hyperpigmented area and processed for light microscopy and for transmission electron microscopy. Light microscopy showed increased melanin pigment with HE staining. Immunohistochemistry with melanocytic markers (HMB-45 and Melan-A) revealed a normal number of melanocytes. Transmission electron microscopy demonstrated normal epidermal structures, such as desmosomes, cytokeratin filaments and hemidesmosomes. With high magnifications an irregular melanossomal contour was seen, with some indentations in their outline.

Scanning Electron Microscopy of the Inner and Outer Aspects of Tiger Tail Hairs.

Background: Tiger tail hairs, Morse hairs or pili annulati is a nonsyndromic hair shaft disorder, characterized by alternating light and dark bands along the hair shaft. Methods: The outer surface and the inner structure of longitudinally cut tiger tail hairs were examined with scanning electron microscopy. Results: Hair specimens of five affected individuals showed small surface undulations with "curtain-like" folding of the hair cuticula (microcanaliculi). In the inner surface cord-like linear structures with serpiginous, tortuous traject were seen, associated with some cavities. Conclusions: These findings suggest that this condition is due to some deficient protein synthesis/arrangement, not only due to cavities in the hair cortex. The term Tiger tail hair is a descriptive clinical term of little scientific rigor. This disorder has been reported mainly as pili annulati; however, rings are not observed. In analogy to pili canaliculi, in which well-formed grooving is observed in the hair surface, we suggest the term pili microcanaliculi to describe this condition, based in the ultrastructural findings.

Ultrastructural aspects of the skin in lipoid proteinosis (Urbach-Wiethe disease).

Lipoid proteinosis is a rare autosomal recessive disease, characterized by hyaline deposits of PAS-positive material in tissues due to mutations in the ECM1 gene. This study evaluated the ultrastructure of the skin of a 6-year-old child affected by this condition. The light microscopy identified PAS-positive hyaline deposits, which were more intense in the papillary dermis. Scanning electron microscopy of the dermis showed a compact papillary dermis and fibrillar deposits in the middle dermis. Transmission electron microscopy clearly showed the deposition of fibrillar material in the dermis, forming clusters adherent to elastic fibers, between the collagen bundles and the collagen fibers, and also filling up the cytoplasm of dermal fibroblasts.

Ecthyma-like phaeohyphomycosis caused by Cladosporium cladosporioides.

A case of cutaneous phaeohyphomycosis caused by Cladosporium cladosporioides in a 50-year-old housewife is described. The clinical presentation was an ecthyma-like crusted lesion on the back of her left hand. Scanning electron microscopy of the culture showed the conidiophores and the limoniform or ellipsoidal conidia, with a slightly verrucous surface. The lesion was removed surgically, with no relapses after 6-month follow up.

Scanning Electron Microscopy of Subclinical Gefitinib-Induced Hair Changes.

Oral inhibitors of epidermal growth factor receptor may have a wide range of cutaneous manifestations. Hair manifestations are observed in 10%-20% of the patients. At the ultrastructural level erlotinib-induced hair changes were already described as acquired pili torti et canaliculi. We examined a 78-year-old female patient, with lung carcinoma, taking gefitinib for 15 months. The treatment has no side effects with good tolerance and tumor response. Although the patient had not observed any change on the hairs under the therapy, some specimens were obtained to be examined in natura with scanning electron microscopy. Under low magnification incipient grooving was observed on the hair surface, tortions or angulations of the hair shaft were not found. With higher magnifications the surface grooving was even more evident. Our findings show that gefitinib may cause subclinical hair changes, similar to those described at the ultrastructural level with erlotinib.

Light and electron microscopy of eruptive collagenoma.

Connective tissue nevi may be multiple or solitary, sporadic or familial. Eruptive collagenoma is a variant of the acquired collagenomas characterized by multiple sclerotic papules with an acute onset. A 13-year-old girl reported that in the past year, small asymptomatic lesions began to appear in her skin, 30 lesions were seen in the trunk, 5 in the cervical region and 1 in the face. Light microscopy with hematoxylin and eosin staining showed sparse collagen fibers, with Weigert staining diminished elastic tissue was observed. Scanning electron microscopy of the dermis showed individualized collagen fibers forming waved compact masses and not bundles. Transmission electron microscopy also showed sparse and loose collagen fibers with different diameters in cross sections.

Scanning Electron Microscopy of Erlotinib-induced Hair Changes: Pili Torti et Canaliculi.

The cutaneous toxicity of the epidermal growth factor receptor inhibitors, such as erlotinib, is associated with a wide range of manifestations, such as papulopustular eruptions, xerosis, paronychia, and changes in the growth pattern of hair and nails. Hair manifestations are seen in 10%-20% of the patients. A female patient taking erlotinib for lung cancer for 8 months noticed that her scalp hair became rough on palpation and that her eyelashes were elongated. Some scalp hairs were cut and proximal and distal portions were examined in natura with scanning electron microscopy. Torsions and important grooving were seen in the proximal portions, but not in distal hair portions. Erlotinib-induced hair changes are pili torti et canaliculi.

Elastic tissue damage in cephalic acquired cutis laxa.

Cutis laxa is a rare condition characterized by diminished elastic tissue. We report the histological changes from a 22-year-old male patient, who presented since 4 years hanging and inelastic facial skin, giving him an older appearance. The palpebral, preauricular and submandibular skin obtained after a facelift were examined. Conventional light microscopy with hematoxylin-eosin staining showed perivascular lymphocytic infiltrates and crossed-over collagen fibers. With Weigert staining, a lessening of elastic fibers with fragmentation, shortening and clumping was seen. The oxytalanic fibers in the papillary dermis were also affected, ranging from absence or reduction to flattening with clumping of the fibers, giving an irregular contour to the basal membrane zone. These findings were more intense in the palpebral skin. Transmission electronic microscopy showed reduction of the elastic fibers, a granular degeneration of the elastic tissue was found and collagen fibers were normal. Similar to light microscopy, at the ultrastructural level, the basal membrane has an irregular contour.

Scar sarcoidosis with a 50-year interval between an accident and onset of lesions.

Cutaneous sarcoidosis has been reported to develop in scars. We report an unusual case of sarcoidal granuloma formation in scars that had been present for 50 years.

Localized cutaneous leishmaniasis of the plantar region: a 40-year outcome.

We report the case of a 78-year-old male Brazilian farmer, who presented with an extensive ulcer on the right foot that had an erythematous and raised border. This ulcer involved most of the right plantar region and had persisted for more than 40 years. Satellite erythematous papules and tumor-like growths were also seen on the right ankle. Extracutaneous involvement was not found. Light microscopy showed epithelial hyperplasia and diffuse histiocyte infiltration with intense plasmocytosis. Cultures for fungi and Leishmania were negative. The polymerase chain reaction with specific primers for Leishmania was performed using DNA extracted from the lesions; it showed an amplification of 120 pB. The patient had an excellent response after two 20-day cycles of intra-venous N-methylglucamine antimonate (15 mg/Kg/day). Leishmaniasis should be highly considered in the differential diagnosis of chronic ulcers in endemic areas.

Prevalence and associated factors with sunscreen use in Southern Brazil: A population-based study.

BACKGROUND: Sunscreen use is important for the prevention of skin cancer, but population-based information about its prevalence and associated factors are scarce in Brazil. OBJECTIVE: We sought to evaluate the prevalence and associated factors with sunscreen use among Brazilian adults. METHODS: We conducted a cross-sectional population-based study with a representative sample of adults aged 20 years or older living in the urban area of the city of Pelotas, Southern Brazil. We evaluated sunscreen use at the beach, at work, and during outdoor sports, for at least 20 minutes between 10 am and 4 Pm, from December 2004 to March 2005. The outcome measure was dichotomized in individuals who never used sunscreen, and those who used sunscreen, regardless of frequency. RESULTS: Prevalence of sunscreen use at the beach, work, and outdoor sports was 60.8% (95% confidence interval 55.6-66.0), 13.7% (95% confidence interval 10.7-16.6%), and 30.2% (95% confidence interval 24.1-36.3), respectively. At work, the median number of days of exposure was 70 days, whereas at the beach it was 10, and for sports it was 16. Women, whites, those with higher educational achievement, and those with higher income were more likely to use sunscreen. LIMITATIONS: No data on adequacy of sunscreen use were gathered. CONCLUSION: Our data show that the individuals most exposed to sunlight are those who use sunscreen the least. Interventions targeting this group are required, because this is also the population with the lowest socioeconomic level.

Cutaneous metastasis of pheochromocytoma in multiple endocrine neoplasia IIB.

Pheochromocytoma is a rare tumor originating from neuroectodermic cells. Only 10% of these tumors are malignant. There are many familial forms of this tumor, including multiple endocrine neoplasia type II, Von Hippel-Lindau syndrome, and neurofibromatosis type I. Skin manifestations of pheochromocytoma are rare, and cutaneous metastasis in patients with multiple endocrine neoplasia IIB has never been described. The case of a patient with multiple endocrine neoplasia IIB who presented malignant pheochromocytoma with multiple cutaneous metastasis is described.

The many faces of phytophotodermatitis.

Phytophotodermatitis is a common cutaneous phototoxic reaction produced by contact with a variety of plant substances, followed by sunlight exposure. Phytophotodermatits can simulate child abuse, impetigo, superficial lymphangitis, and larva migrans. The most frequent presentation is hyperpigmentation of the dorsum of the hands, but there are other less common findings such as blisters or lesions mimicking solar lentigines and melasma.

Pitted keratolysis.

Pitted keratolysis is a skin disorder that affects the stratum corneum of the plantar surface and is caused by Gram-positive bacteria. A 30-year-old male presented with small punched-out lesions on the plantar surface. A superficial shaving was carried out for scanning electron microscopy. Hypokeratosis was noted on the plantar skin and in the acrosyringium, where the normal elimination of corneocytes was not seen. At higher magnification (x 3,500) bacteria were easily found on the surface and the described transversal bacterial septation was observed.