DISCUSSION OF QUESTIONS 1-7

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Answers to Self-Assessment examination of the American Academy of Dermatology Identification No. 800-205 May 2000 issue of the Journal of the American Academy of Dermatology

DISCUSSION OF QUESTIONS 1-7 Pseudoxanthoma elasticum (PXE) is an inherited disorder of abnormal, slowly progressive calcification of elastic fibers. It commonly affects the skin, eyes, and blood vessels with marked clinical heterogeneity. Most patients inherit PXE through an autosomal recessive pattern, but autosomal dominant inheritance patterns have been identified. There is a 2:1 female predominance with onset occurring in childhood (average age, 13 years). PXE of the skin presents as multiple, symmetric, yellow papules and plaques on flexural areas, most commonly the lateral aspect of the neck, antecubital fossa, axillae, and popliteal fossa. The lesions have a cobblestone appearance and are often described as "plucked chicken skin" or "Moroccan leather." Histopathologic examination of cutaneous lesions reveals fragmented and calcified elastic fibers in the mid and lower dermis. The calcification appears basophilic on routine hematoxylin-eosin stain, but special stains for calcium, such as Verhoeff-van Gieson stain, should be used to confirm the diagnosis ofPXE. Ocular involvement in PXE includes angioid streaks, peau d'orange pigmentation of the retina, and retinal hemorrhage. Angioid streaks, the hallmark of this disease, are found in other disorders, including sickle cell anemia and Paget's disease of the bone. They are caused by calcification of Bruch's membrane of the retina, which leads to cracking and breaking of the membrane. Ocular changes can be found in most affected adults and may cause loss of central vision. PXE can also affect the vascular system when calcification of the elastic media of blood vessels takes place. Claudication, hypertension, and gastrointestinal hemorrhage are some of the complications seen in PXE. The genetic defect as well as the cause of PXE has yet to be elucidated. Research suggests that the calcification of elastic fibers is a secondary event caused

either by accumulation or abnormal production of extracellular matrix proteins. Although PXE is not a curable disease, preventive measures can change the course of the disease. These include low calcium diet, control of serum lipids, avoidance of head contact sports, and avoidance of aspirin products. For this series the recommended choices are as follows: 1, b; 2, c; 3, b; 4, d; 5, d; 6, a; 7, e. Jo-Ann M. Latkowski, MD M. Joyce Rico, MD New }brk, New York BIBLIOGRAPHY Lebwohl M, Neldner K, Pope FM, DePaepe A, Christiano AM, Boyd CD, et al. Classification of pseudoxanthoma elasticum: report of a consensus conference.J Am Acad DermatoI1994;30:103-7. Neldner KH. Pseudoxanthoma elasticum. Clin DermatoI1988;6:1159.

DISCUSSION OF QUESTIONS 8-13 Disseminated superficial actinic porokeratosis (DSAP) is the most common type of porokeratosis and may be inherited in an autosomal dominant fashion with reduced penetrance in early age. Lesions of DSAP are most frequently evident in sunexposed areas, and the extensor surfaces of the extremities are the most common site of involvement. The face is usually spared. In some instances, lesions are distributed in areas not exposed to the sun. Individual lesions are small and generally annular, with a raised, hyperkeratotic peripheral ridge, and pruritus is present in approximately half of cases. DSAP lesions usually manifest in the third or fourth decade of life, with an equal frequency in both men and women. The peripheral keratotic ridge corresponds histologically to the cornoid lamella, a parakeratotic column within a keratin-filled epidermal invagination. In the underlying epidermis, the keratinocytes are irregularly arranged and have pyknotic nuclei. There is often no granular layer at this site. The cornoid

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lamella of DSAP is somewhat less pronounced than that found in classical, plaque-type porokeratosis of Mibelli. Sunlight appears to be prerequisite for development of DSAP lesions. Lesions have also developed after phototherapy for psoriasis or after the frequenting of tanning booths. DSAP may also be noted in association with immunosuppression, particularly after kidney transplantation. Studies of p53 gene expression have shown that a large percentage of DSAP cases overexpress the tumor-suppressor oncoprotein in the epidermis beneath the cornoid lamella. The risk of malignant degeneration of porokeratotic lesions is well documented and occurs in approXimately 7.5% of patients. The risk of malignant transformation appears to be higher in variants displaying relatively larger, chronic lesions (especially linear porokeratosis) and is much lower in DSAP. Bowen's disease, squamous cell carcinoma, and, rarely, basal cell carcinoma have all been reported to develop within porokeratotic lesions. 'freatment of DSAP with topical 5-fluorouracil or cryotherapy has been effective in many cases. Retinoids have had less consistent results. There have been anecdotal reports of success with the use of vitamin D analogs, including topical tacalcitol. For this series the recommended choices are as follows: 8, d; 9, c; 10, d; 11, c; 12, c; 13, c. Roger H. Weenig, MD Henry W Randle, MD, PhD Rochester, Minnesota Jacksonville, Florida BIBLIOGRAPHY Bohm M, Luger TA, Bonsmann G. Disseminated superficial actinic porokeratosis: treatment with topical tacalcitol. J Am Acad DermatoI1999;40:479-80. Kanitakis J, Euvrard S, Faure M, Claudy A. Porokeratosis and immunosuppression. Eur J Dermatol 1998;8:459-65. Sasson M, Krain AD. Porokeratosis and cutaneous malignancy: a review. Dermatol Surg 1996;22:339-42.

DISCUSSION OF QUESTIONS 14·18 Routine histologic staining of cutaneous biopsy sections is usually performed with hematoxylineosin. With this staining method, nuclei stain basophilic (blue), and collagen, muscles, and nerves stain eosinophilic (red). When other structures or materials need to be demonstrated, special stains can be employed.

The von Kossa stain is used to identify calcium, which is stained black. The Masson trichrome stain identifies collagen with blue or green; nuclei, muscles, and nerves are dark red. Elastic fibers are stained black, collagen red, and nuclei, muscles, and nerves are yellow with the Verhoeff-van Gieson stain, which is used primarily to identify the elastic fibers. The Warthin-Starry stain identifies the presence of spirochetes, which are black. Alkaline Congo red is used to stain amylOid pink-red, with green birefringence in polarized light. For this series the recommended choices are as follows: 14, d; 15, e; 16, b; 17, c; 18, a. Mary C. Spellman, MD San Diego, California BIBLIOGRAPHY Elenitsas R, Van Belle Po Elder D. Laboratory methods. In: Elder D, Elenitsas R, Jaworsky C, Johnson B, editors. Lever's Histopathology of the skin. 8th ed. Philadelphia: LippincottRaven; 1997. p.51-60.

DISCUSSION OF QUESTIONS 19·28 Clinical changes in the human nail unit are frequently observed by patients and providers and often cause tremendous concern. Although nails can respond to many internal and external stimuli with few morphologic changes, categorizing the problem properly is expedited by the knowledge of accurate descriptive terminology. Onychoschizia, or splitting of the nails into layers parallel to the surface, often results from repeated wetting and drying of nails. This seems to be more frequent in female than male persons. Onychorrhexis, or excessive longitudinal striations of the nails, may be due to variations in the turnover rate of the matrix cells and is rarely a functional problem. Onychorrhexis has been found in association with gout, hemochromatosis, hypothyroidism, lichen planus, peripheral vascular disease, psoriasis, Reiter's syndrome, and scleroderma. Onychomadesis, the separation of the nail plate from the nail bed, may occur in epidermolysis bullosa or as a result of conditions such as severe pustular psoriasis or toxic epidermal necrolyis. Chemotherapeutic agents have also been implicated in the development of onychomadesis. Ingrown nails, or onychocryptosis, results from the nail plate piercing the nailfold. Onychocryptosis is caused by improper cutting of the nails or external pressure from poorly fitted

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footwear, as well as other mechanical causes. It is a significant cause of pain with ambulation and may be a cause of other morbidities such as infection in an elderly patient who also has diabetes mellitus. Distal and/or lateral separation of the nail from the nail bed is termed onycholysis. The affected area may appear yellowish because of air under the nail and the debris that accumulates there. Onycholysis may be due to trauma, bacterial or fungal infection, eczematous disorders, psoriasis, or it may be photoinduced in association with drugs such as tetracyclines, phenothiazines, or psoralens. Color changes in the nail unit, or chromonychia, may range from white to brown to green to red and can be attributed to a vast array of systemic disorders, dermatologic conditions, drugs or ingestants, or local agents. Generally, the nail unit is asymptomatic, and the color change is of concern only as it relates to its origin and its cosmetic appearance. Pachyonychia refers to thickening of the entire nail plate and may be found idiopathically in older persons. It has also been described in association with acanthosis nigricans, acromegaly, arteriosclerosis, repeated trauma, and some rheumatologic conditions, among other causes. Onychauxis refers to localized nail plate hypertrophy and is therefore distinct from pachyonychia. Paroncyhia, or inflammation of the nailfolds, may be infectious or noninfectious and is often further classified as acute or chronic. Acute infectious paronychias are commonly due to Staphylococcus aureus, streptococci, and Pseudomonas organisms, whereas chronic disease is often complicated by Candida. li"auma, contactants, drug reactions, psoriasis, and eczema may be predisposing factors for the development of paronychia. Hapalonychia refers to soft nails, and trachyonychia refers to rough nails with a sandpaper texture and appearance, as found in twenty-nail dystrophy. For this series the recommended choices are as follows: 19, d; 20, c; 21, b; 22, a; 23, e; 24, a; 25, c; 26, e; 27, b; 28, d.

Mary C. Spellman, MD San Diego, California OIOUOGRAPHY DeBerker DAR, Baran R, Dawber RPR. Handbook of diseases of the nail and their management. Boston: Blackwell Science ltd; 1995. Scher RK, Daniel CR, editors. Nails: therapy, diagnosis, surgery. 2nd ed. Philadelphia: WB Saunders; 1997.

DISCUSSION OF QUESTIONS 29·33 Vitamin A (retinol) deficiency, or phrynoderma, is associated with the clinical symptoms of poor night vision, scaliness of the skin, sebaceous and sweat gland atrophy, follicular plugging, conjunctival xerosis, Bitot spots in the eyes, impaired bone growth, and cranial nerve lesions. Liver disease or fat malabsorption may lead to vitamin A deficiency. Dietary retinol is found in fish, milk, eggs, green leafy vegetables, and liver. Pellagra, or vitamin B3 (niacin) deficiency, is best remembered for "the four Os": diarrhea, dementia, dermatitis, and death. Casal necklace, dermatitis in sun-exposed areas, angular stomatitis, glossitis, and weakness are also documented. Niacin deficiency may be caused by drugs (isoniazid, sulfonamides, anticonvulsants, chloramphenicol, 6-mercaptopurine, 5-fluorouracil), alcohol abuse, malabsorption, carcinoid syndrome, or plain corn diet. Niacin is found in cereals; two thirds of niacin is synthesized from tryptophan. Vitamin B6 (pyridoxine) deficiency clinically presents with periorificial dermatitis, pellagra-like rash, seborrhea, polyneuritis, gastrointestinal symptoms, cheilosis, glossitis, confusion, and lymphopenia. Associated drugs include isoniazid, hydralazine, and penicillamine; uremia and cirrhosis are also causative factors. Pyridoxine is contained in most classes of food. Vitamin B12 (cobalamin) deficiency is associated with hyperpigmentation at the neck, axillae, fingers, other hyperpigmented macules, glossitis, poliosis, megaloblastic anemia, paresthesias, ataxia, and mental status changes. Decreased intrinsic factor production, pernicious anemia, tropical sprue, strict vegetarianism, chronic alcoholism, or ileal bypass are causative factors. Cobalamin is present in animal products. Scurvy, a deficiency of vitamin C (ascorbic acid), presents with follicular hyperkeratosis, perifollicular plugging, "corkscrew" hairs, poor wound healing, koilonychia, gingival hemorrhage, weakness, and depression. Scurvy results from inadequate intake of citrus fruits or oral supplements. Other well-documented vitamin deficiencies include vitamin B1 (thiamine), which may have either cardiac (wet beriberi) or neurologic (dry beriberi) manifestations, orogenital dermatitis, and Wernicke-Korsakoff encephalopathy. Vitamin B2 (riboflaVin) deficiency clinically manifests with angular cheilitis, oculo-orogenital syndrome, seborrheic dermatitis, anemia, and mental retardation. Vitamin

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D deficiency is recognized by the presence of rickets and muscle weakness. Biotin (vitamin H) deficiency appears similar to zinc deficiency, with acrodermatitis enteropathica, intertriginous and periorificial dermatitis, conjunctivitis, glossitis, cheilitis, xerosis, alopecia, and neuropsychiatric symptoms. Vitamin K deficiency is associated with intracutaneous and systemic hemorrhage. Folic acid deficiency is similar to vitamin B12 deficiency, with hyperpigmentation, glossitis, angular cheilitis, and megaloblastic anemia.

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For this series the recommended choices are as follows: 29, e; 30, b; 31, d; 32, a; 33, c. Mary C. Spellman, MD

San Diego, California BIBLIOGRAPHY Mallory 58, Leal-Khouri S. An illustrated dictionary of dermatologic syndromes. New York: Parthenon Publishing Group; 1994. Miller SJ. Nutritional deficiency and the skin. J Am Acad Dermatol 1989;21:1-30.

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