Background  Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes syndrome is a rare multisystem paraneoplastic condition associated with plasma cell dyscrasia. Methods  From our institution's dysproteinemia database, 107 patients met criteria for polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes syndrome between January 1, 2000, and October 1, 2009. Medical records were reviewed for documented syndrome features at diagnosis. We assessed prevalence of skin findings and associations between dermatologic and other characteristic disease findings. Results  Of the 107 patients, 96 (90%) had a recognized cutaneous manifestation. Hyperpigmentation and hemangioma were most common (47%), followed by hypertrichosis (38%). Vascular skin changes - acrocyanosis (34%), Raynaud phenomenon (20%), hyperemia/erythema (20%), flushing (16%), or rubor (11%) - occurred in 62%; white nails, sclerodermoid changes, and clubbing occurred in 30%, 26%, and 6%, respectively. Mean number of skin findings per patient was 2.9 (median, 3.0; range, 0-7). Presence of cutaneous manifestation was associated with abnormal pulmonary function tests (P < 0.001); immunoglobulin G gammopathy was associated with hyperpigmentation and hypertrichosis. No other significant associations were seen. Conclusions  The high prevalence of skin findings (90%) shows the value of dermatologic evaluation in diagnosis of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes syndrome. Our data indicate new associations between skin findings and other disease characteristics.

To systematically review the literature evaluating efficacy and adverse events of propranolol treatment for infantile hemangiomas, we searched the MEDLINE and Cochrane databases for all studies examining the response of infantile hemangiomas (IHs) to propranolol published between June 12, 2008, and June 15, 2012. Forty-one studies with 1,264 patients were included; 74% of patients were female and approximately 30% had received other treatments before propranolol. Propranolol was initiated at a mean age of 6.6 months at a mean dose of 2.1 mg/kg/day and for a mean treatment duration of 6.4 months. The response rate for patients with IHs treated with propranolol was 98% (range 82%-100%), with response rate defined as any improvement with propranolol. Treatment response rates were comparable for studies evaluating IHs at specific sites, such as periorbital IHs. Studies that followed patients after treatment completion reported IH rebound growth in 17% of patients. There were 371 adverse events reported in 1,189 patients. The most common adverse events were changes in sleep (n = 136) and acrocyanosis (n = 61). Serious adverse events were rare, with reports of symptomatic hypotension in five patients, hypoglycemia in four, and symptomatic bradycardia in one. This systematic review of 1,264 patients treated with propranolol for IHs showed a high rate of efficacy and a low rate of serious adverse events.

Primary chilblains are an idiopathic cold-induced vasculopathy affecting the soft tissues of the hands and feet. Secondary chilblains occur in different forms of vasculitis and chronic autoimmune connective tissue disorders. Idiopathic chilblains are rarely reported in children and may generate significant anxiety to doctors and patients. We describe a cluster of idiopathic chilblains encountered over the winter of 2010 in Perth, Western Australia.This is a retrospective review of patients identified from a prospectively compiled database of all new cases seen in our department. Data on history, examination, investigations, prescribed treatments and outcomes were collected.Thirty-two patients with isolated idiopathic chilblains were included, including 20 females and 12 males with a median age at onset of 13.5 years. Lesions were papular with signs of peripheral vasoconstriction causing acrocyanosis, and uncomfortable due to pain and/or pruritis in most. Thickening of the small joints was common where lesions involved these areas. Ulceration of lesions also occurred in some. One patient required hospitalisation for secondary bacterial infection. Most received some form of treatment including non-steroidal anti-inflammatory drugs, prednisolone or nifedipine. Most patients improved spontaneously with warmer weather or responded to cold protection advice. All had resolved completely by late spring (November).Our cluster of chilblains was associated with an unusually cold winter in Perth 2010. It is the largest series reported in the literature, suggesting that chilblains may be more common than previously thought. Chilblains are almost always benign in nature and patients are systemically well and usually need no further investigation and only symptomatic treatment. Prompt recognition can avoid excessive investigation and anxiety, allowing appropriate simple advice and treatment.

Eating disorders, which include anorexia nervosa, bulimia nervosa, and eating disorder not otherwise specified, are psychiatric disorders with physical complications. Several factors may contribute to the onset of anorexia nervosa and bulimia nervosa, including a familial predisposition to these disorders as well as individual personality characteristics. Dissatisfaction with body shape and an overwhelming desire to be thin are considered as risk factors for the development of eating disorders. Skin signs are the expression of the medical consequences of starvation, vomiting, abuse of drugs, such as laxatives and diuretics, and psychiatric morbidity. They include xerosis, lanugolike body hair, telogen effluvium, carotenoderma, acne, hyperpigmentation, seborrheic dermatitis, acrocyanosis, perniosis, petechiae, livedo reticularis, interdigital intertrigo, paronychia, acquired striae distensae, and acral coldness. The most characteristic cutaneous sign of vomiting is Russell sign (knuckle calluses). Symptoms due to laxative or diuretic abuse include adverse reactions to drugs. Symptoms due to psychiatric morbidity (artefacta) include the consequences of self-induced trauma. The role of the dermatologist in the management of eating disorders is to make an early diagnosis of the "hidden" signs of eating disorders in patients who tend to minimize or deny their disorder.

Oxalosis is a disease caused by the deposition of calcium oxalate in extrarenal tissues, most commonly bone, myocardium, retina, blood vessels, and skin, causing the clinical manifestations of the disease. Involvement of the blood vessels of the skin can give rise to livedo reticularis, acrocyanosis, ulcers, and gangrene. We present the case of a 60-year-old woman with a history of recurrent renal lithiasis that had led to terminal renal failure requiring hemodialysis and, subsequently, peritoneal dialysis. The patient developed tender red-violaceous skin discoloration of sudden onset, consistent with livedo reticularis; the lesions progressed to form ulcers. Skin biopsy revealed oxalate vasculopathy. In this article we describe the characteristics of this rare disorder, its differentiation from calciphylaxis, and the therapeutic options.

A 4-month-old male infant was brought to the emergency department because of striking petechial skin lesions and acrocyanosis. Routine hematology revealed leukocytosis and thrombocytosis and the infant was admitted for further investigations. Laboratory findings showed no evidence of infection, and a bone marrow aspirate demonstrated a normal number of immature cells of all lineages. Coagulation and routine biochemistry analyses were within the normal range. Three months later, the infant developed signs and symptoms of encephalopathy with episodes of hypotonia and an altered state of consciousness. A brain magnetic resonance imaging suggested the possibility of an inborn error of metabolism. The urinary organic acid and acylcarnitine profile indicated ethylmalonic encephalopathy. Mutation analysis of the ethylmalonic encephalopathy 1 (ETHE1) gene confirmed the diagnosis of ethylmalonic encephalopathy at the molecular level.

Ethylmalonic encephalopathy (EE) is a rare autosomal recessive disorder caused by mutations in the ETHE1 gene and characterized by chronic diarrhea, encephalopathy, relapsing petechiae and acrocyanosis. Nephrotic syndrome has been described in an infant with EE but the renal histology findings were not described in previous reports. We report a Palestinian girl with EE who presented with chronic diarrhea, encephalopathy, petechial rash and acrocyanosis. Subsequently, she developed progressive deterioration of renal function caused by rapidly progressive glomerulonephritis resulting in death within few days. This is, to our knowledge, the first reported occurrence of rapidly progressive glomerulonephritis in a child with ethylmalonic encephalopathy. Its presence is a serious complication associated with poor prognosis and may be explained by the diffuse vascular damage.

ABSTRACT:

A sixty year old male presented with dark urine, symptomatic anaemia and peripheral gangrene following cold exposure. Investigations revealed that he had haemolysis and serological evidence of recent Epstein Barr virus infection. Although acrocyanosis is commonly associated with cold agglutinin disease, gangrene is a rare complication. Management of secondary cold agglutinin disease is mainly supportive.

Ethylmalonic encephalopathy (EE) is a rare autosomal recessive disorder characterized by early onset encephalopathy, chronic diarrhoea, petechiae, orthostatic acrocyanosis and defective cytochrome c oxidase (COX) in muscle and brain. High levels of lactic, ethylmalonic and methylsuccinic acids are detected in body fluids. EE is caused by mutations in ETHE1, a mitochondrial sulphur dioxygenase. By studying a suitable mouse model, we found that loss of ETHE1 leads to accumulation of sulphide, which is a poison for COX and other enzymatic activities thus accounting for the main features of EE. We report here the first autopsy case of a child with a genetically confirmed diagnosis of EE, and compare the histological, histochemical and immunohistochemical findings with those of the constitutive Ethe1 (-/-) mice. In addition to COX depleted cells, widespread endothelial lesions of arterioles and capillaries of the brain and gastrointestinal tract were the pathologic hallmarks in both organisms. Our findings of diffuse vascular damage of target critical organs are in keeping with the hypothesis that the pathologic effects of ETHE1 deficiency may stem from high levels of circulating hydrogen sulphide rather than the inability of specific organs to detoxify its endogenous production.

CREST syndrome is part of the heterogeneous scleroderma group of autoimmune diseases that cause thickening, hardening and tightening of the connective tissue in different parts of the body, and it may lead to complex disorders. CREST syndrome is characterized by the coexistence of calcinosis, Raynaud's phenomenon, esophageal hypomotility, sclerodactily and telangectasia. A 72-year-old caucasian woman is referred to the S. Gerardo Hospital of Monza, with a chief complaint of oral pain and difficulties in deglutition and eating, associated with denture instability and difficulties to fit it. She had been previously diagnosed with Raynaud's phenomenon, and afterwards with CREST syndrome. Extra-oral examination underlined taut, thickened and rigid skin, pallid-red irregular maculae all over the face, telangiectasias and acrocyanosis. Intra-oral examination showed no alteration of the mucosa, but we can observe tongue rigidity and some speckled red alternating with white spots on the hard palate and in the vestibule. We undermitted the patient the dental treatment of Sjogren's syndrome. The management of the Sjogren's syndrome is symptomatic and empirical, and involves the use of saliva secretion stimulators, salivary substitutes and coadjuvants. Dental treatment and prophylaxis are important to prevent the consequences of xerostomia, such as rampant caries, based on the administration of topical fluoride in toothpastes and rinses, and supplemented by fluoride gels and varnishes. Instruction and reinforcement of oral hygiene, along with frequent dental assessment and management by the dentist are essential measures to preserve the oral health of those affected with CREST syndrome in progression to SS, complicated with Sjogren's syndrome.