Review DOI: 10.6003/jtad.1374r1 Dermatologic Manifestations of Neurologic Disease Ümit Türsen,* MD, Belma Türsen,** MD Address: *Mersin University, Medical Faculty, Dermatology Department, **Mersin Hospital, Dermatology Department, Mersin, Turkey. E-mail: [email protected] * Corresponding Author: Dr Ümit Türsen, Mersin University, Medical Faculty, Dermatology Department, 33079- Mersin Published: J Turk Acad Dermatol 2013; 7 (4): 1374r1. This article is available from: http://www.jtad.org/2013/4/jtad1374r1.pdf Key Words: Dermatology, manifestation, neurology Abstract Background: Many diseases present with both neurologic and dermatologic manifestations. Eight such clinical cases are presented, along with clinical photographs of the skin lesions, in the format of a self-evaluation. Each case is followed by a discussion and a brief review of the characteristic cutaneous and neurologic findings. The intent is to demonstrate classic dermatologic manifestations of diseases seen by neurologists. Introduction light the more common skin changes that occur in association with stroke, peripheral Many disorders have a combination of neurologic and dermatologic findings in neuropathy, meningitis, encephalitis, malig- patients. This manuscript provides an nancy and HIV. overview of neurocutaneous disorders and organizes them into clinically relevant groups In addition, we cover the most frequently of use to the practicing physician. Many encountered neurocutaneous conditions and neurological conditions are accompanied by finally, we will remind the reader of skin skin changes, which frequently appear before changes associated with adverse reactions to the onset of the neurological symptoms. In drugs commonly used by neurologists. This some cases a rash may herald the start of an article aims to cover the most important and infectious process. In others, skin changes meaningful dermatological disorders that you may mirror pathological processes that are also occurring in the brain or peripheral may encounter within neurology. An ex- nerves. Careful examination of the skin can haustive list of all potential cutaneous findings therefore provide important clues when would not necessarily be useful in diagnosis making a neurological diagnosis, allowing early and management; rather, we aim to provide a treatment and avoiding unnecessary tests. practical selection of management altering Instead of presenting an exhaustive list of dermatological signs within the context of cutaneous manifestation of every neurological condition, we aim to provide practical common neurological presentations. We also knowledge for the non-dermatologist to aid review some commonly encountered neuro- neurological differential diagnosis. We high- cutaneous disorders, skins lesions at different Page 1 of 19 (page number not for citation purposes) J Turk Acad Dermatol 2013; 7 (4): 1374r1. http://www.jtad.org/2013/4/jtad1374r1.pdf stages of HIV/AIDS and remind the reader of Telangiectasias are best seen on the lips, ton- important drug reactions [1,2]. gue, nose and fingers [1]. 4. Angiokeratomata: It is characterised by small red or black vascular malformations. A-Neurocutaneous Disorders Associated Fabry's disease is a rare X linked recessive With Stroke disorder caused by a deficit in the enzyme In young patients, the skin can provide im- α-galactosidase, resulting in deposition of portant clues as to the cause of stroke [1,2]. glycolipids in blood vessels and various or- There are some skin manifestations in pati- gans. There is multisystem involvement. ents with stroke as belows; Typically patients are male, presenting in childhood or early adolescence with painful 1.Livedo reticularis (Cutis marmorata): It neuropathy and in adulthood with ischae- is characterised by mottled red–blue disco- mic strokes. Discrete angiokeratomata ap- louration, net-like appearance, especially pear in a ‘bathing suit’ distribution early in over the legs, and exacerbated by cold. Livedo disease and usually before any neurological reticularis is not uncommon in young women symptoms [1]. and can be completely benign. However, it 5. Lax stretchy skin/hypermobility: Pseu- may indicate an underlying hyperviscosity doxanthoma elasticum is associated with syndrome or vasculitis. It appears in 25% of premature atherosclerosis and aneurysm those with systemic lupus erythematosus formation. It manifests cutaneously as patc- and antiphospholipid syndrome and is a hes of lax redundant skin like plucked chic- common association of vasculitis involving ken appearance, typically around the neck medium sized vessels like polyarteritis no- and inguinal folds. Arterial dissection and dosa and small sized vessels like cryoglobuli- aneurysm formation also occur in Ehlers– nemia. Sneddon's syndrome is characterised Danlos syndrome type IV as a result of de- by widespread livedo reticularis in associa- fective collagen, which causes thin trans- tion with multiple strokes. Here, patients lucent skin, easy bruising and joint hyper- tend to have high titres of antiphospholipid mobility [2]. antibodies and typically livedo reticularis de- 6. Xanthomata and xanthelasmata: It is velops several years before stroke. Patients characterised by yellow papules and plaques with polycythaemia may appear plethoric with cholesterol deposits [2]. and, in addition to livedo, often complain of itchy skin, especially when exposed to warm 7. Varicella zoster infections: On rare oc- water [3]. casions following trigeminal shingles, vari- cella zoster virus may infect arteries in close 2. Purpura: Purpura is non-blanching red or proximity to the trigeminal ganglion and purple macular lesions. A petechia is a small, cause ischaemic stroke [2]. less than 1-2 mm diameter, red or purple spot on the body, caused by a minor hemorr- 8. Diabetic skin manifestations: Dermato- hage. Purpura and petechia from bleeding be- logical examination can also provide clues to neath the skin are common in the older the more common risk factors for stroke. patient but may be significant in young pati- Dyslipidemia commonly manifests in the ents with stroke. Frequently, this indicates skin, especially familial forms. Neurologist small vessel vasculitis and platelet disorders, should look specifically for tendon xantho- including thrombotic thrombocytopenic pur- mata, xanthelasmata, eruptive xanthomata pura [2]. and palmar striae. And they do not forget to look for nicotine stained fingers and hair. 3. Telangiectasia: Telangiectasia is small Diabetes mellitus has many cutaneous mani- vascular lesions, prone to haemorrhage. He- festations, including necrobiosis lipoidica dia- reditary haemorrhagic telangiectasia is cha- beticorum (a well demarcated waxy yellow/ racterised by telangiectasia of the skin and brown plaque, usually on the shins, with sur- mucosal linings of the nose and gastrointes- face telangiectasia and ulceration), non-spe- tinal tract, with brain involvement in 10% of cific dermopathy (red/brown discolouration cases. Most patients complain of nosebleeds. often over the knees), blisters or acanthosis Page 2 of 19 (page number not for citation purposes) J Turk Acad Dermatol 2013; 7 (4): 1374r1. http://www.jtad.org/2013/4/jtad1374r1.pdf nigricans (velvety pigmented skin in body the first event. Patients without antibodies, folds) [2]. who had recurrent abortions as their first event, were at lowest risk. The study reported that recurrent events are of the same type as Antiphospholipid Syndrome the presenting symptom. Therefore, initial cli- Antiphospholipid syndrome is a hypercoagu- nical features can help predict the prognosis lable state resulting from antibodies that ne- of the disorder. Specific clinical features tend utralize anionic phospholipids on endothelial to cluster during the course of the disease. A cells and platelets. It is a multisystemic disor- variety of therapies have been tried. Use of der, and patients may present with a wide long-term anticoagulants to maintain the in- range of neurologic manifestations, fetal loss, ternational normalized ratio at 3 or greater mild thrombocytopenia, valvular heart di- may help prevent recurring thromboembo- sease, and livedo reticularis. Antiphospholi- lism. Aspirin is of clinical benefit and may pid syndrome is associated strongly with help decrease the incidence of fetal loss in systemic lupus erythematosus (SLE) and pa- some patients. Plasmapheresis and cyclop- tients with SLE are considered to have secon- hosphamide have been used. Ancrod (purified dary antiphospholipid syndrome. The term pit viper venom) has been used successfully primary antiphospholipid syndrome is reser- in one patient. A review of clinical and labo- ved for cases of unknown etiology. The disor- ratory characteristics of 50 patients by Asher- der is characterized by high titers of anti- son et al described a 70% survival rate in phospholipid antibodies (APLA), ie, lupus an- patients treated with anticoagulation, stero- ticoagulant and anticardiolipin antibodies. ids, and treatments that decrease antiphosp- Studies suggest that antibodies are not direc- holipid antibodies, such as plasmapheresis ted against phospholipids but are directed at and/or intravenous IgG. Statins have been phospholipid-binding proteins such as B2- used in antiphospholipid syndrome because glycoprotein I and prothrombin. The cuta- of their antithrombotic, anti-inflammatory, neous manifestations most commonly seen and pleiotropic effects on vascular endothe- include livedo reticularis and leg ulceration. lium. Statins may block