Small vessel disease in primary familial brain calcification with novel truncating PDGFB variants.

INTRODUCTION: Primary familial brain calcification (PFBC) is a neurodegenerative disease characterised by bilateral calcification in the brain, especially in the basal ganglia, leading to neurological and neuropsychiatric manifestations. White matter hyperintensities (WMH) have been described in patients with PFBC and pathogenic variants in the gene for platelet-derived growth factor beta polypeptide (PDGFB), suggesting a manifest cerebrovascular process. We present below the cases of two PFBC families with PDGFB variants and stroke or transient ischaemic attack (TIA) episodes. We examine the possible correlation between PFBC and vascular events as stroke/TIA, and evaluate whether signs for vascular disease in this condition are systemic or limited to the cerebral vessels. MATERIAL AND METHODS: Two Swedish families with novel truncating PDGFB variants, p.Gln140* and p.Arg191*, are described clinically and radiologically. Subcutaneous capillary vessels in affected and unaffected family members were examined by light and electron microscopy. RESULTS: All mutation carriers showed WMH and bilateral brain calcifications. The clinical presentations differed, with movement disorder symptoms dominating in family A, and psychiatric symptoms in family B. However, affected members of both families had stroke, TIA, and/or asymptomatic intracerebral ischaemic lesions. Only one of the patients had classical vascular risk factors. Skin microvasculature was normal. CONCLUSIONS: Patients with these PDGFB variants develop microvascular changes in the brain, but not the skin. PDGFB-related small vessel disease can manifest radiologically as cerebral haemorrhage or ischaemia, and may explain TIA or stroke in patients without other vascular risk factors.

Visual perception, cognition, and error in dermatologic diagnosis: Key cognitive principles.

Dermatologic diagnosis relies on vision primarily and auditory and verbal input secondarily. Accurate dermatologic diagnosis is predicated on seeing and perceiving a skin finding, categorizing and naming the finding correctly, and comparing the visual data and data obtained from the totality of the clinical encounter (ie, from other sensory modalities) with one's working mental database of dermatologic diagnoses. The baseline assumption-which is false-is that a dermatologist is an expert at each of the aforementioned steps and transitions sequentially between them seamlessly in an error-free fashion. Each of these steps has inherent challenges, and the transitions between steps can also be problematic. In part 1 of this 2-part report, we describe the pitfalls associated with visual recognition. In part 2, we discuss cognitive heuristics as they relate to the dermatologic diagnostic process and prevention of diagnostic error.

A 65-Year-Old Female from Connecticut with Orf Infection.

The virus, which causes orf and induces acute pustular skin lesions in sheep and goats, is transmissible to humans yet is rarely observed in North America. We present a case of a 65-year-old female farmer from Connecticut who contracted orf from her sheep. The clinical and histopathologic features, important to arrive at the correct diagnosis of this uncommon yet important infection, are described. We also discuss the benign nature of this condition and emphasize that treatment is not required.

Skin manifestations of endocrine and neuroendocrine tumors.

The skin signs of benign and malignant endocrine and neuroendocrine tumors are manifold and early identification of these dermatologic features is crucial in initiating timely diagnosis and management. This article reviews the salient cutaneous features of these tumors that arise in the classic endocrine glands, lung and gastrointestinal tract either as individual neoplasms or as part of a syndrome.

Hypertrophic lupus erythematosus: the diagnostic utility of CD123 staining.

CD123-positive plasmacytoid dendrocytes are prominent in the infiltrate of discoid lupus erythematosus (LE). We hypothesized that these cells would also be present in hypertrophic LE and would aid in the histopathologic distinction from squamous cell carcinoma (SCC) and hypertrophic actinic keratosis (AK). Five cases of hypertrophic LE and 10 cases each of SCC and hypertrophic AK were stained with CD123. A heavy band of CD123-positive cells was present at the epidermal-dermal junction in all cases of hypertrophic LE, and only single or rare scattered clusters of CD123-positive cells were seen in SCC and actinic keratoses. The pattern of CD123 staining can be a useful feature to distinguish hypertrophic LE from SCC and hypertrophic AK.

Nephrogenic systemic fibrosis.

Nephrogenic systemic fibrosis, initially called nephrogenic fibrosing dermopathy, has been strongly linked to exposure to gadolinium-based contrast media used in magnetic resonance imaging in patients with renal insufficiency. This review discusses recent advances in our understanding of the pathophysiology and clinical approach to patients with chronic kidney disease who require diagnostic imaging with gadolinium-based contrast media.

Akhenaten and the strange physiques of Egypt's 18th dynasty.

Akhenaten was one of Egypt's most controversial pharaohs, in part because of his strange appearance in images produced after he had declared Aten, the Sun-disc, his one-and-only god. Whether these were symbolic representations or realistic ones that indicate a deforming genetic disorder is the subject of continuing debate. The authors present evidence that the bizarre physical features portrayed in these images are not only realistic but were shared by many members of Egypt's 18th Dynasty. The features are best explained by either 2 different familial disorders-the aromatase excess syndrome and the sagittal craniosynostosis syndrome-or a variant of the Antley-Bixler syndrome caused by a novel mutation in one of the genes controlling the P450 enzymes, which regulate steroidogenesis and cranial bone formation.

A randomized, double-blind, placebo-controlled trial of photopheresis in systemic sclerosis.

BACKGROUND: Systemic sclerosis is a multisystemic connective tissue disease with marked involvement of the skin and joints for which few effective evidence based therapies are available. To further investigate the efficacy of extracorporeal photochemotherapy on early aggressive cutaneous disease, a randomized, double-blind, placebo-controlled trial was performed. OBJECTIVE: Our aim was to evaluate the efficacy of photopheresis in the treatment of patients with systemic sclerosis (scleroderma). METHODS: This randomized, double-blind, placebo-controlled clinical trial was conducted at 16 investigational sites in the United States, Canada, and Europe. Sixty-four patients with typical clinical and histologic findings of scleroderma, of less than 2 years' duration, were studied. Patients did not receive any other concomitant treatment for scleroderma. Patients were randomized to receive either active or sham photopheresis treatment on two consecutive days monthly for 12 months. Severity of skin (skin scores assessed in 22 body regions) and joint involvement (60 joints examined for contractures) were assessed on a monthly basis. RESULTS: A statistically significant improvement in skin scores as compared with baseline was observed at 6 months (P = .0024) and 12 months (P = .008) among those who received active photopheresis, but not among those who received sham photopheresis. Comparison of skin scores between the two study arms did not achieve statistical significance because of the small sample size of the study arms. Joint involvement was also significantly improved after 6 months (P = .002) and 12 months (P = .001) of active photopheresis when compared with baseline. LIMITATIONS: The study lacks sufficient statistical power to reveal a significant difference in skin and joint manifestations between the active and sham photopheresis arms. CONCLUSION: Photopheresis induced significant improvement of skin and joint involvement in patients with scleroderma of recent onset; however, any effect when compared with sham treatment and a possible placebo effect may be modest.

Epidermolysis bullosa acquisita and multiple myeloma.

The coexistence in the same patient of epidermolysis bullosa acquisita (a rare, autoimmune, acquired mucocutaneous blistering disorder) and multiple myeloma (a plasma cell neoplasm) is extremely uncommon. We describe a patient in whom both of these diseases occurred simultaneously. Intravenous immunoglobulins were used to treat both diseases.

Skin manifestations of internal malignancy.

This article concentrates on the major signs and syndromes that are associated with internal malignancies in the geriatric population. Included are cutaneous metastases, ectopic adrenocorticotropic hormone-producing syndromes, and disorders arising from APUD cell tumors. The major paraneoplastic disorders of dermatomyositis, generalized pruritus, Bazex's syndrome, and acanthosis nigricans also are discussed. Also included are Bowen's disease of skin; arsenical toxicity; and the Peutz-Jeghers', Gardner's, and Torre's syndromes, which are indicative of systemic or organ-related carcinogens.