The use of cinacalcet for the treatment of calciphylaxis in patients with chronic kidney disease: A comprehensive review

Calciphylaxis is a rare but life-threatening condition, most commonly affecting patients with stage 4 or 5 chronic kidney disease. No universally accepted therapy exists so far. In an attempt to avoid surgical intervention with parathyroidectomy, which is of questionable efficacy and carries several risks, a number of noninvasive treatments have been trialled with variable success. These treatments are aimed at modifying risk factors for calciphylaxis, in particular hypercalcaemia, hyperphosphataemia and hyperparathyroidism. The aim of this review was to summarise the available evidence to determine the potential role of cinacalcet in the treatment of calciphylaxis in patients with chronic kidney disease. Demographic, clinical and laboratory data were retrospectively collected from the available English and non-English literature. Overall, there was a very high response rate (partial or complete) of calciphylaxis lesions to both cinacalcet monotherapy and cinacalcet as part of a combination therapy (83.4% and 82.8%, respectively). When examining complete response to treatment specifically, combination therapy with cinacalcet proved more efficacious than monotherapy (62.1% versus 41.7%). There was also an associated rapid reduction of intact parathyroid hormone over a period of 2–33 months in both groups. While there are limitations as to how our data can be interpreted due to the heterogeneity of the methods and follow-up of the included case reports and case series, prompt and consistent therapy including cinacalcet may help improve the disease outcome. Additional research needs to be performed in this area, to further define the optimal use of cinacalcet for the treatment of calciphylaxis.     

双下肢钙化防御一例

患者,女,56岁。双小腿红斑、结节、溃疡伴疼痛3个月。病史、临床表现结合组织病理学诊断为钙化防御。患者经治疗疼痛症状略改善,皮损无明显好转,2个月后失访。     

CALCIPHYLAXIS IN A RENAL DIALYSIS PATIENT WITH SECONDARY HYPERPARATHYROIDISM

A fatal case of extensive skin ulceration and infarction with metastatic calcification in the cutis, subcutis, and vessels is presented in an Aboriginal woman with chronic renal failure and secondary hyperparathyroidism. Parathyroidectomy and debridement of skinulcers with grafting were performed, but the patient died of septicaemia. Heparin induced necrosis was considered in the differential diagnosis and excluded.     

Fulminant and relentless cutaneous necrosis with excruciating pain caused by calciphylaxis developing in a patient undergoing peritoneal dialysis

A 50-year-old Japanese female with chronic renal failure who had been on continuous ambulatory peritoneal dialysis developed fulminant systemic cutaneous necrosis that began as painful livedo reticularis-like skin lesions on her thighs. Because of disseminated vascular calcification within the muscular layer of her lower limbs, we eventually diagnosed her with calciphylaxis. The skin necrosis progressed rapidly, and she died of sepsis and pneumonia on the 53rd hospital day. In addition to her long-lasting severe hyperparathyroidism and extremely elevated serum phosphorus and calcium levels, mechanical, frictional stimulation inflicted on the local skin and administration of corticosteroids were suspected to have precipitated the calciphylaxis. Our lack of awareness of this disease in its early stages resulted in our missing the chance to do a parathyroidectomy that might have changed the course. It is important to know the clinical features of this rare disease in order to make a diagnosis as early as possible.     

Diffuse dermal angiomatosis associated with calciphylaxis in a patient with end‐stage renal disease

Diffuse dermal angiomatosis (DDA) represents a benign, acquired, reactive proliferation of vessels. DDA is clinically characterized by painful livedoid plaques with central ulceration, and the histopathologic hallmark is diffuse endothelial cell hyperplasia in the dermis. DDA has been rarely reported in association with calciphylaxis, a condition characterized by calcification of arterial walls with accompanying thrombosis and cutaneous necrosis. We present a case of a 72‐year‐old man with end‐stage renal disease on peritoneal dialysis who presented with painful lesions on his legs, and was found to have DDA in the setting of calciphylaxis. The possible pathogenesis linking DDA and calciphylaxis is discussed.     

Study of three complementary techniques for measuring cutaneous hydration in vivo in human subjects: NMR spectroscopy, transient thermal transfer and corneometry – application to xerotic skin and cosmetics

Background/aims: The aim of this study was to determine the capability and the analytical quality of three different in vivo, non‐invasive, quantitative methods for measuring skin hydration: two innovative methods that have been used for more than eight years – nuclear magnetic resonance spectroscopy (NMR‐S) and transient thermal transfer (TTT) – and the more widely used and conventional corneometry. Methods: The work presented evaluated the capability and precision, as well as cutaneous exploration depths, of the three methods. Experiments were carried out in vivo following the hydration, in kinetic terms, induced by topic application of reference moisturizing products. Spatio‐temporal efficacy of a lipolotion was also studied by the TTT method. Cases of xerotic skin were studied with TTT and corneometry. Results: The results obtained showed better repeatability and reproducibility with the TTT and NMR‐S methods than with corneometry. NMR‐S is one of the only direct hydration measurement methods. It measures skin hydration down to the outer dermis with high precision. It is indicated for products having an action down to the deep cutaneous layers. By changing thermal power parameters, the TTT method can determine hydration to the outer, middle or deep epidermal layers. It is, therefore, possible to track the penetration of products in various layers of the epidermis. The small size of the probe enables the hydration measurement of skin sites (lips, eyelids) that were not, up to now, measurable with the two other methods. Corneometric investigations are restricted to the surface of the horny layer; measurements are easy and rapid but influenced by the composition of products applied to the skin and their phases: aqueous, oily or ionic. The xerotic skin study highlights the importance of exploration in different layers of the epidermis, as dehydration concerns not only the upper layers of the epidermis but also the medial and deep layers. With the TTT method, it has been possible to highlight the penetration dynamics of a lipolotion with, initially, an increase in the hydration in the outer epidermis, followed 3 h later by a transfer from the outer to the middle epidermis. Conclusion: NMR‐S, TTT and corneometry represent three possible ways to assess skin hydration. Because they explore different cutaneous depths, they are more complementary than competitive. Transient thermal transfer, although a semi‐direct method, is a precise, informative, and innovative solution to evaluate skin hydration at different epidermal depths and sites.     

Quantitative research on skin pore widening using a stereoimage optical topometer and Sebutape®

BACKGROUND/AIMS: The treatment of skin pore widening is concerned with cosmetics sciences, but an objective and quantitative measurement method of the severity of skin pore widening has not been developed. In this study, bioengineering methods were applied to evaluate skin pore widening. The results from bioengineering measurements were compared with clinical visual assessment. METHODS: In order to quantify skin pore widening, three-dimensional data of skin pore were produced by a stereoimage optical topometer (SOT). The sizes of follicular infundibulum were measured quantitatively, with reserved sebum by Sebutape. 50 female volunteers were divided into two groups. Group A was tested by the cosmetics including active ingredient and group B by placebo. The constricting effect of skin pores by cosmetics was measured for immediate effect and long-term effect. RESULTS: In the immediate effect, there was no statistical difference between groups A and B in visual scoring. In SOT, the size of the skin pores of group A had changed after application of cosmetics but there were no changes in group B. In the long-term effect, there was no statistical difference between groups A and B in visual scoring. TA, TV, SA, and SV of skin pores of groups A and B were decreased in 3 and 6 months by SOT. In Sebutape measurement, there was decreased volume of reserved sebum in groups A and B. The result of the Sebutape study was similar to that of SOT. CONCLUSION: Evaluation of skin pore change by visual assessment is difficult, but bioengineering tools are more reliable and useful methods for the assessment of skin pore change.     

Urticarial rash,fever, and arthritis: A case of refractory Adult‐onset Still's disease with good response to tocilizumab

Adult‐onset Still's disease (AOSD) is a rare, systemic inflammatory disorder of not completely understood etiology. Aberrant activation of the innate immune system and overproduction of several pro‐inflammatory mediators are considered a critical component in disease pathogenesis. AOSD still poses a challenge due to the broad range of differential diagnoses and no specific biomarkers. Four cardinal symptoms are quotidian spiking fever, joint involvement, evanescent salmon pink‐rash rash, and leukocytosis with neutrophilia. We present a case of a 61‐year‐old female with a recurrent urticarial rash accompanied by attacks of high fever, tender joints, sore throat, enlarged liver, elevated inflammatory reactants, and hyperferritinemia. After an extensive workup, the patient fulfilled the criteria of AOSD. She was refractory to the glucocorticosteroids and disease‐modifying anti‐rheumatic drugs (DMARDs). Finally, after several unsuccessful attempts to achieve disease control with traditional DMAR's administration of Tocilizumab (TCZ), a humanized anti‐IL‐6 receptor antagonist resulted in substantial disease improvement. Since skin manifestations are a common feature of AOSD, it should be among differential diagnoses in patients with skin lesions and constitutional symptoms. Biologic agents represent a significant therapeutic advance in patients with AOSD refractory to conventional therapy.     

Application of the Food and Drug Administration (FDA) bioequivalent guidance of topical dermatological corticosteroid in yellow-skinned Japanese population: validation study using a chromameter

The American Food and Drug Administration (FDA) bioequivalent guidance of topical dermatological corticosteroids in 1995 (the Guidance) requires measurement of the skin blanching response with a chromameter for evaluation of cutaneously applied corticosteroid formulations. The Japanese government decided to apply the same guidelines in 2003, despite there having been no reported trial for the yellow-skinned races. The purpose of this study was to obtain basic data of corticosteroid-induced skin blanching response measured with a chromameter on yellow-skinned races. Four studies were performed according to the Japanese version of the Guidance for Industry using a chromameter on the forearms of healthy Japanese volunteers. This involved: (i) a validation study of proper duration of treatment exposure (dose duration); (ii) a comparison study of two dermatological corticosteroid products that represented different potency classes; (iii) inspection of reproducibility using right and left forearms; and (iv) study of seasonal difference. We showed that: (i) the same medication can give different values of ED(50) (the dose duration required to achieve 50% of the fitted areas under the effect curves [AUEC](max) value) under different dose durations; (ii) ED(50) do not always represent the potency of the corticosteroid; (iii) the results of AUEC at maximum duration were similar, but AUEC at an approximate ED(50) duration time varied widely; and (iv) the results of AUEC were different according to season. In conclusion the dose duration relationships, determination of the AUEC(max), and the ED(50) could be obtained on yellow-skinned races using the FDA method. However, negligible differences were found in our study regarding dose duration, reproducibility and seasonal change.