Calciphylaxis: how specific are the pathological features: avoiding false-positives and false-negatives.

Calciphylaxis is considered a critical inflammatory dermatosis with potentially devastating clinical consequences. Skin biopsies are expedited for evaluation and are often considered as a gold standard for diagnostic confirmation and exclusion of other conditions. The key histopathological features include a combination of vascular and extra-vascular calcifications, intravascular microthrombi, and changes related to resulting ischemia. The pathological diagnosis of calciphylaxis is not always a straightforward process as it can be influenced by a number of factors. The specificity of pathological diagnosis of calciphylaxis has been questioned and a systematic approach with multidisciplinary collaboration is required to avoid potential errors.

Topical sodium thiosulfate for calcinosis cutis associated with autoimmune connective tissue diseases: the Mayo Clinic experience, 2012-2017.

In this case series, we retrospectively identified all patients treated with topical sodium thiosulfate (TST) for calcinosis cutis (CC) associated with underlying autoimmune connective tissue diseases at Mayo Clinic (Rochester, MN, USA) during the period 1 January 2012 to 27 June 2017. Of 28 patients identified (mean age 57.0 years; 96% female), 19 (68%) had clinical improvement of their CC with TST, 7 (25%) had no response and 2 (7%) had unknown response. There were adverse events in three patients: two had skin irritation and the third, who had a zinc allergy, experienced pain with application. Overall, our findings support those of previous case reports that TST appears to be a relatively well-tolerated adjuvant treatment for CC, although future studies with a control group are warranted to assess the true efficacy of TST for the indication of CC.

Perianal purpuric plaques revealing an amyloid light-chain amyloidosis: case report and review of the literature.

Systemic immunoglobulin light chain amyloidosis is the most common and severe type of amyloidosis. There is an abnormal fibrillary protein deposition in tissues that leads to progressive and irreversible organ dysfunction. The most commonly affected organs are kidney and heart. Although rare, cutaneous manifestations may be the first clinical sign of the disease and usually present as hemorrhagic lesions, such as purpura, petechiae, and ecchymosis. We present a 71-year-old man that presented to our department because of exuberant purpuric plaques in the anogenital area as the first manifestation of an amyloid light-chain (AL) amyloidosis. The multi-organ involvement in addition to rapid clinical deterioration precipitated the patient's death four months later.

[The cutaneous porphyrias]. / Porphyries cutanées.

The porphyrias are a group of metabolic disorders resulting from an innate abnormality in haem biosynthesis, and the clinical settings of which vary according to the genetic enzyme abnormality in question. These are genetic disorders with autosomal dominant or recessive inheritance of varying penetrance, and whose clinical expression differs according to the preferential location of haem precursors. Different classifications have been proposed according to genetic inheritance, the enzyme anomaly at issue, and clinical expression. The clinical classification distinguishes between acute porphyria (acute intermittent porphyria, porphyria variegata, hereditary coproporphyria), bullous cutaneous porphyrias (porphyria cutanea tarda, porphyria variegata and hereditary coproporphyria), painful photosensitive acute cutaneous porphyrias (erythropoietic protoporphyria and X-linked dominant protoporphyria), and rare recessive porphyrias (congenital erythropoietic porphyria, Doss porphyria, hepatoerythropoietic porphyria and harderoporphyria). Treatment depends on the clinical expression of the disorder.

The Clinical Spectrum of Multiple Endocrine Neoplasia Type 2A with Cutaneous Lichen Amyloidosis in Ethnic Han Chinese.

This study systematically reviewed previous literatures and analyzed the genotype-phenotype relationship between the multiple endocrine neoplasia type 2A (MEN 2A)-cutaneous lichen amyloidosis (CLA) and RET/OSMR/IL31RA mutations. RET/OSMR/IL31RA screening was performed on 8 RET-carriers from 3 independent Chinese MEN 2A families. Besides, 51 MEN 2A-CLA patients in 116 RET carriers from literatures were clustered and analyzed. Our results indicated that almost all MEN 2A-CLA patients exhibited CLA which was located in the scapular region and carried RET mutation at codon 634. Meanwhile, we firstly described MEN 2A-CLA here in Chinese Han patient with RET p.C634F mutation.

Metastatic calcinosis cutis in a patient with Hodgkin's lymphoma.

Calcinosis cutis results from the deposition of insoluble calcium salts in the skin and subcutaneous tissue. Herein, we report a case of extensive metastatic calcinosis cutis in an 18-year-old woman with stage IV Hodgkin lymphoma with skeletal involvement. With combination therapy including radiation directed at her lymphoma and diltiazem, her lesions improved dramatically. This case demonstrates the previously unreported association between calcinosis cutis and Hodgkin lymphoma.

Calciphylaxis with evidence of hypercoagulability successfully treated with unfractionated heparin: a multidisciplinary approach.

Calciphylaxis is characterized by abnormal calcification of vessels and skin; however, its aetiology and pathogenesis remain unclear. Entities frequently associated with calciphylaxis are end-stage renal disease, diabetes mellitus, hypercalcaemia, hyperphosphataemia, elevated calcium-phosphate product, hyperparathyroidism and possible hypercoagulable states. Skin lesions may remain quiescent or may develop suddenly and progress rapidly. They are more common on the legs. Treatment of calciphylaxis is very challenging and requires interdisciplinary management. We present a case that highlights the difficulty of treating calciphylaxis. A multidisciplinary approach was vital for the proper treatment of our patient. This case also demonstrates the importance of searching for underlying hypercoagulable states, especially in recalcitrant cases. In cases of calciphylaxis with vessel occlusion from microthrombi, heparin therapy would be a logical next step. The effect of anticoagulation may be rapid and impressive.

The important role of epidermal triacylglycerol metabolism for maintenance of the skin permeability barrier function.

Survival in a terrestrial, dry environment necessitates a permeability barrier for regulated permeation of water and electrolytes in the cornified layer of the skin (the stratum corneum) to minimize desiccation of the body. This barrier is formed during cornification and involves a cross-linking of corneocyte proteins as well as an extensive remodeling of lipids. The cleavage of precursor lipids from lamellar bodies by various hydrolytic enzymes generates ceramides, cholesterol, and non-esterified fatty acids for the extracellular lipid lamellae in the stratum corneum. However, the important role of epidermal triacylglycerol (TAG) metabolism during formation of a functional permeability barrier in the skin was only recently discovered. Humans with mutations in the ABHD5/CGI-58 (α/ß hydrolase domain containing protein 5, also known as comparative gene identification-58, CGI-58) gene suffer from a defect in TAG catabolism that causes neutral lipid storage disease with ichthyosis. In addition, mice with deficiencies in genes involved in TAG catabolism (Abhd5/Cgi-58 knock-out mice) or TAG synthesis (acyl-CoA:diacylglycerol acyltransferase-2, Dgat2 knock-out mice) also develop severe skin permeability barrier dysfunctions and die soon after birth due to increased dehydration. As a result of these defects in epidermal TAG metabolism, humans and mice lack ω-(O)-acylceramides, which leads to malformation of the cornified lipid envelope of the skin. In healthy skin, this epidermal structure provides an interface for the linkage of lamellar membranes with corneocyte proteins to maintain permeability barrier homeostasis. This review focuses on recent advances in the understanding of biochemical mechanisms involved in epidermal neutral lipid metabolism and the generation of a functional skin permeability barrier. This article is part of a Special Issue entitled The Important Role of Lipids in the Epidermis and their Role in the Formation and Maintenance of the Cutaneous Barrier. Guest Editors: Kenneth R. Feingold and Peter Elias.

Dietary linoleic acid requirements in the presence of α-linolenic acid are lower than the historical 2 % of energy intake value, study in rats.

Previous studies on rats and human subjects have established that the linoleic acid (LA) requirement is 2 % of the total energy intake (en%), but is obtained in the absence of α-linolenic acid (ALA) and consequently appear to be overestimated. This raises questions since a recent study including ALA has suggested to divide the historical value by four. However, this recent study has remained inconclusive because the animals used were not totally LA-deficient animals. For the first time, the present study was especially designed using physiological and biochemical markers and performed in two steps: (1) to achieve a specific n-6 fatty acid deficiency model using growing male rats fed either a 0 en% from LA/0 en% from ALA (0LA/0ALA), 0LA/0·5ALA or 2LA/0·5ALA diet, born from female rats fed a 0LA/0·5ALA diet; and (2) to refine the required level of LA in the presence of ALA using rats fed either a 0LA/0ALA, 0·5LA/0·5ALA, 1LA/0·5ALA, 1·5LA/0·5ALA diet, born from female rats fed a 0LA/0·5ALA diet. The first step shows that the best LA deficiency model was obtained using rats fed the 0LA/0ALA diet, born from female rats fed the 0LA/0·5ALA diet. The second step demonstrates that in growing rats, LA deficiency was corrected with an intake of 1-1·5 en% from LA and 0·5 en% from ALA. These data suggest that the requirements in humans should be revisited, considering the presence of ALA to set up the recommendation for LA.

Familial hypercholesterolaemia with tuberous and tendinous xanthomas: case report and mutation analysis.

Xanthomas are important clinical manifestations of disordered lipid metabolism, which are mostly found in patients with familial hypercholesterolaemia (FH), an inherited disorder that is predominantly caused by mutations in the low-density lipoprotein receptor gene (LDLR). Tuberous and tendinous xanthomas with wide distribution and large size are rare; however, they may indicate the severity of FH, and tend to be found in homozygous FH. In this study, we investigated the clinical and genetic aspects of a young patient with FH presenting with multiple large masses in various locations. The lesions on the elbows and buttocks were locally excised and subsequently confirmed by biopsy to be xanthomas. Genetic analysis further confirmed that the patient was compound heterozygous for two mutations in both alleles of the LDLR gene. This rare case of compound heterozygous FH presenting with multiple large and widely distributed xanthomas provides a better understanding of FH and xanthomas.

Update on pediatric photosensitivity disorders.

PURPOSE OF REVIEW: Although rare in the pediatric population, photosensitive dermatoses may begin prior to adulthood. The causes of photosensitivity are diverse, ranging from primary, immunologically mediated disorders of photosensitivity to inherited genetic or metabolic disorders. This review will highlight the key features of these disorders to familiarize the pediatric practitioner with their symptoms and any associated extracutaneous clinical or laboratory findings that may accompany them. RECENT FINDINGS: New developments in the field of pediatric photosensitivity have been scant over recent years. While mechanisms of photosensitivity and genetic underpinnings associated with various conditions such as xeroderma pigmentosum continue to be uncovered, the literature on disorders of photosensitivity has been otherwise without many recent significant advances. SUMMARY: Although the differential diagnosis of pediatric photosensitivity disorders is broad, it is often possible to establish the diagnosis by following an algorithmic approach. Once the correct diagnosis is rendered, this will guide any further workup that needs to be performed as well as specific management strategies.

Characteristic dermoscopic features of primary cutaneous amyloidosis: a study of 35 cases.

BACKGROUND: Primary cutaneous amyloidosis (PCA) is a relatively common skin disorder among Asians and South Americans. It is usually diagnosed clinically. However, for cases with atypical presentations, the diagnosis can be a challenge and skin biopsy may be necessary. Dermoscopy has been proved to be a valuable, noninvasive tool in the diagnosis of cutaneous pigmented diseases. Most lesions of PCA show hyperpigmentation and the major histopathological abnormalities of PCA occur in the epidermis and dermal papillae. Dermoscopy might be a powerful tool to provide valuable information for the diagnosis of PCA. OBJECTIVES: We aimed to find characteristic dermoscopic features of PCA. MATERIALS AND METHODS: Cases with typical clinical presentations of PCA, either macular or lichen subtypes, were included in this study. All were evaluated using a hand-held, polarized and nonpolarized dermoscope. RESULTS: A total of 35 patients with clinically diagnosed PCA were enrolled. Eighteen patients had lesions consistent with macular amyloidosis and 17 with lichen amyloidosus. We found two major dermoscopic patterns characteristic of PCA. The most common dermoscopic finding of PCA was a central hub, which could be either white or brown, surrounded by various configurations of pigmentation. For cases of lichen amyloidosus with prominent hyperkeratosis, the central hub was replaced by a scar-like morphology. CONCLUSIONS: This is the first study to report the characteristic dermoscopic features of PCA. We demonstrate that the use of a dermoscope may assist in achieving an accurate diagnosis of PCA.

Assessment of the influence of HLA class I and class II loci on the prevalence of keloid disease in Jamaican Afro-Caribbeans.

Keloid disease (KD) is a common abnormal cutaneous fibrotic disorder of unknown aetiopathogenesis. KD is reported to have a strong genetic component as it is often familial and has a high incidence in certain ethnicities, in particular those of Afro-Caribbean origin. Genetic risk factors combined with aberrant lesional inflammatory responses point to the human leukocyte antigen (HLA) system as a viable target for investigating disease aetiology. Sequence specific primer polymerase chain reaction with allele sequencing was used to determine HLA-DQA1 and DQB1 allele frequencies (AF) for 165 KD patients and 119 healthy controls of black Jamaican Afro-Caribbean origin. HLA class I alleles A*01, A*03, A*25, B*07 and Cw*08:02, previously identified as KD associated in a different ethnicity, were also analysed. Allele sequencing confirmed typing accuracy but no statistically significant differences in AF were identified between KD patients and controls. Furthermore, KD subgroups including patient gender, family history and multiple- or single-site scarring did not show significant allele-disease associations.

Association of primary cutaneous amyloidosis with atopic dermatitis: a nationwide population-based study in Taiwan.

BACKGROUND: Primary cutaneous amyloidosis (PCA) is a pruritic skin disorder most commonly seen in Southeast Asia and South America. Association of PCA with atopic dermatitis (AD) has been reported in the literature. However, no large-scale epidemiological study of PCA and its associations with other diseases has been conducted so far. OBJECTIVES: We aimed to provide overall demographic data and comorbidities of patients with PCA based on a nationwide database in Taiwan. METHODS: Cases of PCA were collected from records of National Health Insurance claims from 2000 to 2007. We analysed patients' gender, age when the diagnosis was first made, and the overall 8-year prevalence. We also investigated comorbidities. RESULTS: The overall 8-year prevalence of PCA was 7·87 per 10,000 persons. Although there was no significant gender difference in the prevalence of PCA, men and women showed a different peak age (men, 71-80 years; women, 41-50 years) and a different age distribution at diagnosis. The mean age at diagnosis of PCA was significantly younger for women than for men. Men sought medical assistance for PCA more frequently than women. There was a higher disease activity from May to September than during other months. PCA was strongly associated with AD (odds ratio 7·18). Patients with PCA had a higher comorbidity of hyperlipidaemia and diabetes mellitus. CONCLUSIONS: This is the first nationwide population-based epidemiological study of PCA. We demonstrate that PCA can be associated with other disorders, especially AD.

The molecular skin pathology of familial primary localized cutaneous amyloidosis.

Familial primary localized cutaneous amyloidosis (FPLCA) is an autosomal dominant disorder associated with chronic itching and skin lichenification. In lesional skin, there are apoptotic basal keratinocytes and deposits of amyloid material on degenerate keratin filaments in the upper dermis. The genetic basis of FPLCA involves mutations in the OSMR and IL31RA genes but the disease pathophysiology is not fully understood. In this study, we identified new pathogenic heterozygous missense mutations in the OSMR gene (p.Val631Leu and p.Asp647Tyr) in two Dutch FPLCA families. We then compared gene expression profiles between FPLCA lesional skin (n = 4) and site-matched control skin (n = 6). There was twofold or greater upregulation of 34 genes and downregulation of 43 genes. Most changes in gene expression (verified by quantitative RT-PCR) reflected alterations in epidermal differentiation and proliferation consistent with lichenification, but we also noted a reduction in several interfollicular keratinocyte stem cell markers in FPLCA skin. Differences in gene expression were also noted for proteins involved in apoptosis and nerve conduction. Collectively, this study expands the molecular basis of FPLCA and provides new insight into the skin pathology of this condition.