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Neurology and the Skin J Neurol Neurosurg Psychiatry 1999;66:417–430 417 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.66.4.417 on 1 April 1999. Downloaded from NEUROLOGY AND MEDICINE Neurology and the skin Orest Hurko, Thomas T Provost Many disorders aVect both the nervous system Five per cent to 10% of patients with HIV and the skin. The complementary—and some infection will develop herpes zoster radiculitis, would say—diametrically opposite—clinical with painful dermatomal shingles, which in methods of the dermatologist and the neurolo- rare patients disseminates over the entire body gist can in these circumstances reduce an oth- (fig 1).4 Kaposi’s sarcoma has been associated erwise dauntingly large diVerential into a more with herpes type VIII. Unlike the classic indo- tractable, smaller list. Often triangulation with lent Kaposi’s sarcoma detected in elderly East- these and other clinical findings is suYcient for ern European Askenazi Jews, this rapidly accurate diagnosis, but in other cases, serologi- growing tumour is seen in young homosexuals, cal or genetic data must be considered before but not in AIDS associated with a parenteral diagnosis is secure. mode of infection (drug misuse, inadvertent We have purposely avoided traditional needle stick, etc). Rarely, disseminated infec- groupings such as phakomatoses, and immunological, infectious, or genetic diseases. tion with cryptococcus resulting in cutaneous Such distinctions are becoming increasingly lesions resembling molluscum contagiosum obscure. Instead, we have organised the may be an AIDS defining event. Surprisingly, roughly 300 disorders with manifestations both patients with this complication may have few or in the skin and nervous system into clinically no systemic features. relevant groupings, as they may be first Neurological disorders related to AIDs are encountered by a practicing physician: neuro- reviewed elsewhere.45 Syphilis, discussed cutaneous disorders associated with impaired below, is another important neurocutaneous immunity; stroke; neuropathy; meningitis or complication of AIDS. meningoencephalitis; vesicular lesions; ecchy- moses, non-palpable purpura, and petechiae; cafe au lait spots; amyloidosis; rheumatoid arthritis; cutaneous vasculitis; photosensitivity; Neuroscience and melanoma. For disorders mentioned only Research, SmithKline in the tables, or not at all, the reader is referred http://jnnp.bmj.com/ Beecham to the encyclopaedic text of Fitzpatrick et al1 Pharmaceuticals, 23 New Frontiers Science and more specialised compendia. Park North H25/124, Third Avenue, Harlow, Neurocutaneous disorders of impaired Essex, UK O Hurko immunity AIDS Eighty five per cent of those aVected with Department of on October 2, 2021 by guest. Protected copyright. Dermatology, The AIDS have skin lesions, the most common of Johns Hopkins which are infectious, the result of impaired cell University School of mediated immunity. Even such banal infections Medicine, 10 th Floor, 550 North Broadway, as verruca vulgaris and molluscum contagio- Baltimore, MD, USA sum are problematic. Both types of viral infec- T T Provost tion are resistant to therapy. Giant mollusca may disseminate over the body. Tinea corporis Correspondence to: and recurrent bacterial infections, especially Dr Orest Hurko, Neuroscience Research, Staphylococcal aureus, may occur. The most SmithKline Beecham common cutaneous manifestation, however, is Pharmaceuticals, New recalcitrant seborrheic dermatitis, a chronic Frontiers Science Park North H25/124, Third Avenue, inflammation typically of the scalp and face, Harlow, Essex CM19 5AW, but which can also involve the intermammary UK. Telephone 0044 1279 region of the chest, groin, and axilla. It is 622 739; fax 00441279 622 371; email thought to result from infection by Pityrospo- [email protected] rum orbiculare, a saprophytic organism. Usu- ally, it can be successfully suppressed by Received 14 August 1998 continued use of topical ketoconazole. and in revised form 9 November 1998 Herpes zoster is an AIDS defining event for Figure 1 Grouped vescicles on an erythematous base in a Accepted 10 November 1998 those who test positive for infection with HIV. zonal distribution characteristic of a herpes zoster infection. 418 Hurko, Provost J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.66.4.417 on 1 April 1999. Downloaded from Table 1 Neurocutaneous disorders associated with stroke Disorder Cutaneous Amyloidosis VII Cutis laxa Behçet’s disease Erythema nodosum, genital and oral aphthous ulcers Cerebral cavernous malformations Rarely, angiomas Diabetes mellitus Necrobiosis lipoidica diabeticorum, poorly healing ulcers Endocarditis Petechiae, Osler’s nodes, splinter haemorrhages Fabry disease Angiokeratoma—clusters of punctate dark red to blue black non-blanching macules or papules; symmetric, starting at the umbilicus and knees, then buttocks and scrotum Haemolytic-uraemic syndrome Erythematous necrotic skin lesions Hereditary haemorrhagic telangiectasia Telangiectasias Homocystinuria Sparse hair, malar flush, livedo reticularis, diVuse hypopigmentation Hypercholesterolaemia Xanthomas, xanthelasma Progeria (Hutchinson-Gilford) Aged skin, alopecia, generalised hypotrichosis, sparse or absent eyebrows, scleroderma- like, thin skin, midfacial cyanosis Neurocutaneous angioma Large irregular haemangiomas, angiomas Pseudoxanthoma elasticum Pseudoxanthoma, multiple papules, peau d’orange skin, angioid streaks, subcutaneous calcification usually in blood vessels Systemic lupus erythematosus Photosensitivity, malar rash, telangiectasia, discoid lupus, patchy alopecia, mucosal ulcers, angioneurotic oedema, Raynaud’s phenomenon, subcutaneous nodules, palpable purpura, gangrene, erythema multiforme (rare) Takayasu’s arteritis Cutaneous necrotising venulitis—palpable purpura Werner (Pangeria) Scleroderma-like skin, graying hair and baldness, leg ulcers, progressive scalp alopecia, sparse body hair, telangiectasia, mottled pigmentation, loss of subcutaneous fat, subcutaneous calcification OTHER NEUROCUTANEOUS DISORDERS WITH Neurocutaneous disorders associated IMPAIRED IMMUNITY with stroke (table 1) Similar infections and tumours are common to ANTIPHOSPHOLIPID SYNDROME other immunosuppression from a wide variety The antiphospholipid antibody syndrome is of causes such as chemotherapy, lymphoma, characterised by antibodies that are thought to and in excess of 100 described heritable disor- induce hypercoagulability by neutralising ani- ders in which the immune system is depressed, onic phospholipids on endothelial cells and including severe combined immunodeficiency platelets. These antibodies are most commonly (Swiss or alymphocytic type agammaglobuli- seen in systemic lupus erythematosus but also naemia) with susceptibility to fungal and viral as a primary abnormality. The most common antiphospholipid antibody of pathophysiologi- as well as pyogenic infections; the X-linked cal relevance is directed against epitopes local- Wiskott-Aldrich syndrome of eczema and ised to the cardiolipin 2 glycoprotein I thrombocytopenia; Chediak-Higashi syn- complex. Other antibodies show specificity for drome of partial albinism and neuropathy prothrombin and annexin V.In some instances, related to mutations of a beige-related lyso- antiphospholipid syndrome has been shown to somal traYcking regulator encoded on chro- be a familial trait.6 The two most common tests mosome 1q42; the Griscelli syndrome of employed for detecting antiphospholipid anti- partial albinism with silvery hair and progres- bodies are the anticardiolipin enzyme linked sive leukodystrophy, related to mutations of immunosorbent assay (ELISA) and a func- myosin 5 encoded on 15q21; ataxia tel- tional assay employing the Russell viper venom angiectasia; Bloom syndrome discussed below; test (RVVT). The associated cutaneous mani- 3 and others. festations are livedo reticularis, most com- http://jnnp.bmj.com/ monly on the lower extremities (fig 2); acrocyanosis, a Raynaud’s-like phenomenon, and rarely, Degos malignant atrophic papulo- sis. The combination of livedo reticularis with multiple strokes resulting in dementia has been designated Sneddon’s syndrome. Antiphos- pholipid antibodies are associated with several 7 neurological syndromes, most of which result on October 2, 2021 by guest. Protected copyright. from focal ischaemia.8 FABRY’S DISEASE Fabry’s disease is an X-linked multisystem dis- order resulting from deficiency of ceramide tri- hexosidase (also known as á-galactosidase) and resultant vascular deposition of lipid.39 Af- fected males are easily recognised by a purpu- ric skin rash for which the disorder was given its other name, angiokeratoma diVusum univer- sale. There is a characteristic whorl-like corneal dystrophy of similar severity in hetero- zygotes as in hemizygous males,10 but aVected females almost never have the characteristic skin rash. Without the rash, the diagnosis is often overlooked. The cutaneous manifesta- tions of Fabry’s disease are characterised by Figure 2 Livedo reticularis involving the knees and discrete angiokeratomas most prevalent be- thighs. There is also ulceration on the lower leg. tween the knees and nipples. Neurology and the skin 419 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.66.4.417 on 1 April 1999. Downloaded from a non-specific diabetic dermopathy. The last is characterised by reddish brown macules most commonly over the extensor surfaces of the lower extremities. The more characteristic lesion, however, is necrobiosis lipoidica diabeti-
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