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Cutaneous Markers of Internal Disease SUMMARY SOMMAIRE Cutaneous Markers of Internal Disease Are Les Indices Cutanes Des Maladies Internes Sont Nombreux

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Cutaneous Markers of Internal Disease SUMMARY SOMMAIRE Cutaneous Markers of Internal Disease Are Les Indices Cutanes Des Maladies Internes Sont Nombreux I I R. R. Forsey P. Michael Reardon Cutaneous Markers of Internal Disease SUMMARY SOMMAIRE Cutaneous markers of internal disease are Les indices cutanes des maladies internes sont nombreux. Cet article discute des desordres legion. This artide discusses the pigmentaires, de l'acanthosis nigricans, du prurit, pigmentary disorders, acanthosis nigricans, des xanthomes et du probleme de photosensibilit6, pruritus, the xanthomas and problems of soulignant les procedures appropriees afin d'etablir photosensitivity, outlinng the appropriate un diagnostic d6finitif et, dans certains cas, le procedures to establish a definite diagnosis, traitement de tels patients. and in some cases the management of such patients. (Can Fam Physician 1982; 28:1415-1421). ..I- a' Dr. Forsey is a consultant seen the patient for a long time. The to stimulate overlying melanocytes to dermatologist in the Department of following classification illustrates increase their activity. Dermatology at the Montreal many of the causes of generalized Gastrointestinal. Malabsorption General Hospital, and Dr. Reardon hyperpigmentation. from a variety of causes and biliary is chief resident in the same Endocrine. Addison's disease re- cirrhosis are associated with increased department. Reprint requests to: sults in hyperpigmentation secondary pigmentation.2 Dr. R. R. Forsey, 1414 Drummond to the effect of unsuppressed pituitary Connective Tissue Disease. Sclero- St., Suite 1005, Montreal, PQ. beta melanocyte stimulating hormone derma is occasionally associated with H3G lWl. (B-MSH)1 or cutaneous melanocytes. Addisonian-like pigmentation.2 Asso- Clinically, the pigmentation is diffuse ciated cutaneous signs usually leave but accentuated on exposed areas of little doubt as to the primary diag- T HE SKIN manifestations of inter- the body. Areolae, genitalia, palmar nosis. nal disease are myriad.1 2 The creases, scars and mucus membranes Drugs. Systemically administered usual custom is to present the cutan- are also areas of predilection. Sixteen psoralen in combination with long- eous findings of specific diseases; our percent of patients with Cushing's syn- wave ultraviolet light produces a pho- plan is to present some cutaneous drome, 40% of acromegalics and some totoxic reaction, with the subsequent symptoms and signs which might give patients with adrenogenital syndrome appearance of tremendously increased clues to the diagnosis of systemic dis- and Graves disease display similar pig- pigmentation. Some medications, or ease. mentary findings.2 Control of the un- their metabolic products, may accu- derlying disease usually results in a re- mulate in the dermis and produce pig- Assorted Disorders turn to normal pigmentation. mentation by themselves or by increas- Metabolic. Hemochromatosis is as- ing melanin production. Classic Of Pigmentation sociated with deposition of iron in var- examples include chlorpromazine and Generalized Hyperpigmentation ious parenchymal- organs with secon- heavy metals such as silver (argyria).3 A generalized increase in pigmenta- dary deficiencies of function resulting Malignancy. Some tumors, particu- tion may be quite gradual and not read- in clinical disease. Deposits of iron are larly oat cell carcinoma of the lung, ily apparent to a patient or a close rela- present in the dermis but are not re- have been found to produce MSH-like tive. It may be easily recognized from sponsible for the increase in pigmenta- peptides. Other malignancies, such as old photos, or by a friend who has not tion.1 The presence of iron is believed Hodgkin's disease, will cause hyper- CAN. FAM. PHYSICIAN Vol. 28: AUGUST 1982 1415 pigmentation without an apparent hor- such as pruritus, and even syncope or sive inheritance, absent or decreased monal influence. The very rare gener- death, may occur with widespread re- melanin, nystagmus, photophobia and alized melanosis of metastatic lease of histamine. Although serious decreased visual acuity. The overall malignant melanoma is a grave sign side effects are rare and presumably incidence is approximately 1:20,000. associated with 100% mortality. related to mast cell load, it is advisable All albinos have an increased suscepti- to avoid drugs known to release hista- bility to carcinogenic ultraviolet rays. Localized Hyperpigmentation mine from mast cells (aspirin, co- They should use sunscreens and be ex- Cafe-au-lait spots. These are hyper- deine, opiates and polymyxin B). amined at least yearly for the presence pigmented patches, usually 1.5-20 cm Physical stimuli, such as bathing in hot of premalignant lesions (actinic kera- in diameter. They are frequently pres- water or vigorous rubbing, may also toses) and malignant ones, including ent at birth and have been found to precipitate symptoms. Diagnosis can basal cell carcinoma, squamous cell occur in 10-20% of normal patients. be easily confirmed by biopsy. The carcinoma and malignant melanoma. They often increase in size and number pathologist should be advised of the Two of the rare variants have systemic with age. In children below age five, suspected diagnosis so that stains high- manifestations. In Chediak-Higashi the presence of five or more cafe-au- lighting mast cells will be performed. syndrome, besides the pigmentary ab- lait spots of greater than 0.5 cm is Regular antihistamines by themselves, normality, there is a leucocyte chemo- diagnostic of neurofibromatosis.4 In or in combination with H2 receptor an- tactic defect, increased susceptibility adults or older children, six or more le- tagonists (Cimetidine), are useful in to infection, convulsions, neuropathy sions greater than 1.5 cm are diagnos- treatment. Recently, the use of oral and a propensity to develop pancyto- tic.5 At least 90% of the patients with disodium cromoglycate has been penia and lymphoreticular 'malig- this disease have 1-4 mm spots in the found useful in systemic disease.7 nancy. In Hermansky Pudlak syn- axillae (Crowe's sign).6 The impor- drome, a hemorrhagic diathesis secon- tance of these cutaneous markers is Generalized Hypopigmentation dary to platelet abnormality may that they occur before the development Complete. Congenital generalized occur. of cutaneous neurofibromas. hypopigmentation of the skin,9 hair Partial. Localized hypopigmenta- The clinical presentation of neurofi- and eyes is usually related to a defi- tion occurs due to a variety of causes. bromatosis may be extremely variable. ciency in the synthesis of melanin (al- It is frequently seen as a response to It may be asymptomatic or grossly de- binism). Other conditions including various cutaneous and systemic dis- bilitating, resulting in retardation, sei- homocystinuria, phenylketonuria, eases. It is seen in localized sclero- zures, or a variety of benign and even Menkes kinky hair syndrome and histi- derma (morphea), lichen sclerosis at malignant tumors. The patient and dinemia may also produce such hypo- atrophicus, ash leaf macule of tu- available relatives should be assessed pigmentation and can be ruled out by berous sclerosis, post-inflammatory for related skin, eye, neurological and specialized metabolic assessment. The conditions, some infections (e.g. lep- musculoskeletal findings. Genetic word albino is derived from the Latin rosy, tinea versicolor) and vitiligo. counselling should be offered as no cu- word albus,8 meaning white. There are The diagnosis is often self-evident. rative treatment is currently available. several variants to this condition, all Vitiligo has been reported in associ- ation with thyroiditis, Grave's disease, Pigmentation with urtication. When having in common autosomal reces- the clinician sees a patient with tan colored macules, papules or nodules, Fig. I he should scratch one or more of these Multiple caf6-au-lait spots of Fig. 2 lesions. A positive reaction (Darier's neurofibromatosis. Extensive neurofibromas. sign) is specific for the diagnosis of cutaneous mastocytosis (urticaria pig- mentosa). Mast cells are ubiquitous cells of connective tissue, usually found in small numbers in a perivascu- lar distribution. However, localized accumulation of mast cells may occur in skin and internal organs. These le- sions are most common in children (usually appearing in the first three to nine months of life) and may be soli- tary or multiple. They are rarely asso- ciated with more ominous involvement of bone, internal organs or the blood stream. Adults have a higher incidence of systemic disease and much less ten- dency to the spontaneous resolution normally seen in childhood cases. Immunologic and non-immunologic stimuli will induce these cells to re- lease a variety of products, most not- ably histamine. Marked symptoms, 1416 CAN. FAM. PHYSICIAN Vol. 28: AUGUST 1982 Addison's disease, pernicious anemia, Pseudo-acanthosis nigricans nosis. Malignant acanthosis nigricans diabetes mellitus and alopecia areata.9 This is present in many otherwise tends to follow the course of the under- We believe these associations are rare well, obese patients; it is mild and dis- lying tumor and may regress or pro- and treatment of the underlying condi- appears after weight loss. Some dark- gress according to the treatment. tion does not restore skin color. skinned people residing in tropical cli- It should be clear from the afore- There is a localized congenital hy- mates develop a similar condition due mentioned classification that the pres- popigmentation which frequently re- to perspiration and sweating, as do ence of lesions morphologically con- sembles the leaf of the mountain ash some
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