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.

[Primary hyperoxaluria: case report and therapeutic perspectives].

Primary hyperoxaluria (PH) is a rare genetic disorder with autosomal recessive transmission, characterized by high endogenous production and markedly excessive urinary excretion of oxalate (Ox). It causes the accumulation of calcium oxide crystals in organs and tissues including bones, heart, arteries, skin and kidneys, where it may cause oxalo-calcic nephrolithiasis, nephrocalcinosis and chronic renal failure. Some forms are secondary to enteric diseases, drugs or dietetic substances, while three primitive forms, caused by various enzymatic defects, are currently known: PH1, PH2 and PH3. An early diagnosis, with the aid of biochemical and genetic investigations, helps prevent complications and establish a therapeutic strategy that often includes liver and liver-kidney transplantation, improving the prognosis of these patients. In this work we describe the clinical case of a patient with PH1 undergoing extracorporeal hemodialysis treatment and we report the latest research results that could change the life of patients with PH.

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.

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.

Uremic frost: a harbinger of impending renal failure.

Uremic frost is a striking cutaneous finding seen in patients with severe kidney disease. Familiarity with this condition can be a life-saving signal to initiate urgent dialysis. Uremic frost generally occurs at blood urea nitrogen levels of approximately 200 mg/dl, although it may arise with less severe uremia. Recently confirmed urea transporters in the skin may play a role in the development of uremic frost. Alternatively, damage to the cutaneous microvasculature and pilosebaceous units, as seen in chronic kidney disease, could account for the high levels of urea deposited outside the skin. The treatment of uremic frost is largely aimed at correcting the underlying cause of uremia and the other life-threatening conditions associated with renal failure.

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.

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.

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.

Localized primary cutaneous nodular amyloidosis: case report.

Amyloidosis results from deposition of fibrous and insoluble amyloid protein in extracellular spaces of organs and tissues. Amyloid deposition can be localized or systemic and either primary or secondary. We report a case of localized primary cutaneous nodular amyloidosis manifested by papular-nodular, reddish-brown lesions affecting the nasal area, without evidence of systemic involvement. Immunohistochemistry showed the presence of immunoglobulin kappa light chain.

An unusual presentation of macular amyloidosis.

Macular amyloidosis is a form of cutaneous amyloidosis characterized by dusky-brown lesions usually located on the upper back between the shoulder blades. This report describes the case of a 45 year-old female presenting with hyperpigmented macules and lace-like, non-pruritic erythema in the sacral and cervical region as well as on both arms and legs. Histology revealed amyloid deposits in the papillary dermis which exhibited apple-green birefringence after Congo red staining. There were no systemic findings. This is a case of macular amyloidosis with an unusual presentation. The literature on the subject is also reviewed.

Diffuse plane xanthomatosis associated with monoclonal gammopathy.

Diffuse plane normolipemic xanthomatosis (DPNX) is a rare, non-inherited disease that is often associated with systemic diseases, mainly malignant hematological (especially multiple myeloma) or lymph proliferative disorders. The DPNX can precede the appearance of such conditions by several years, so careful follow-up and periodic laboratory examinations are recommended even for patients that seemed to have no underlying disease. We describe a case associated with monoclonal gammopathy. This case shows that dermatological lesions can be the first manifestation of important hematological diseases and so physicians should be familiarized with this entity.

Amiloidose localizada cutânea primária nodular: relato de caso / Localized primary cutaneous nodular amyloidosis: case report

A amiloidose resulta da deposição de proteína amiloide fibrosa e insolúvel em espaços extracelulares de órgãos e tecidos. O depósito da substância amiloide pode ser localizado ou sistêmico e pode ser de natureza primária ou secundária. Relataremos um caso de amiloidose localizada cutânea primária nodular, manifesta por lesões pápulo-nodulares, eritêmato-acastanhadas, acometendo a região nasal, sem evidência de acometimento sistêmico. O estudo imunoistoquímico demonstrou presença de imunoglobulinas de cadeia leve kappa.

Amyloidosis results from deposition of fibrous and insoluble amyloid protein in extracellular spaces of organs and tissues. Amyloid deposition can be localized or systemic and either primary or secondary. We report a case of localized primary cutaneous nodular amyloidosis manifested by papular-nodular, reddish-brown lesions affecting the nasal area, without evidence of systemic involvement. Immunohistochemistry showed the presence of immunoglobulin kappa light chain.