BOARD REVIEW ANSWERS
1. ATAXIA-TELANGIECTASIA
Difficulty walking and these conjunctival lesions developed during childhood. Which statement is true?
b) The incidence of cancer in homozygotes is 100 times that in age-matched controls
The disease is inherited as an autosomal recessive trait. Cancers develop in affected homozy- gotes at a rate approximately 100 times higher than in unaffected age-matched subjects. Het- erozygotes, who make up approximately 1% of the population, also have an increased cancer risk, especially for breast cancer in women.The increased risk of neoplasia may be related to the unusual sensitivity to ionizing radiation (but not UV radiation) of cells derived from both homozygotes and heterozygotes. Pigmented bands in the retina are a marker for Gardner’s syndrome.
References
Greenberger S, Berkun Y, Ben-Zeev B, Levi YB, Barziliai A, Nissenkorn A. Dermatologic manifestations of ataxia-telangiectasia syndrome. J Am Acad Dermatol. 2013;68(6)932-936. Anheim M,Tranchant C, Koenig M.The autosomal recessive cerebellar ataxias. N Engl J Med. 2012;366(7):636-646.
2. TLR-MEDIATED INFLAMMATORY RESPONSE
The inflammatory response to Propionibacterium acnes is thought to be mediated through which toll-like receptor (TLR)?
a) TLR2
P acnes is a major etiological factor in acne. It appears to trigger an inflammatory response in part through the activation of TLR2. Such activation results in the production of proinflammatory cytokines and chemokines by monocytes, which leads to the development of inflammatory acne lesions.
Reference
Dispenza MC,Wolpert EB,Gilliland KL,et al.Systemic isotretinoin therapy normalizes exaggeratedTLR-2-mediated innate immune responses in acne patients.J Invest Dermatol. 2012;132(9):2198-2205.
3. LEIOMYOMAS (HEREDITARY LEIOMYOMATOSIS/RENAL CELL CANCER SYNDROME)
These grouped, painful papules are a key feature of an autosomal dominant condition associated with:
c) Renal cancer
The hereditary leiomyomatosis/renal cell cancer syndrome is an autosomal dominant condition characterized by multiple leiomyomas of the uterus and skin in conjunction with papillary renal cell carcinoma.The renal tumors are associated with early spread to lymph nodes and a poor prognosis.The disease appears to result from a mutation of the gene encoding fumarate hydratase, an enzyme of the tricarboxylic acid cycle.
References
Shen Z, Hoffman JD, Hao F, Pier E. More than just skin deep: faciocutaneous clues to genetic syndromes with malignancies. Oncologist. 2012;17(7):930-936. Thiers BH, Sahn RE, Callen JP. Cutaneous manifestations of internal malignancy. CA Cancer J Clin. 2009;59(2):73-98.
4. LUPUS ERYTHEMATOSUS
Which is usually the first antibody system to appear in patients with this disease? a) Antinuclear antibodies
Autoantibodies are often first detected years before the first clinical manifestations of lupus erythematosus.Antinuclear antibodies generally appear first, with the others following sequentially as listed in (b) through (e): antiphospholipid antibodies, anti-dsDNA antibodies, anti-Sm antibodies and anti-nRNP antibodies.
References
Liu Z, Davidson A.Taming lupus-a new understanding of pathogenesis is leading to clinical advances. Nat Med. 2012;18(6):871-882. Arbuckle MR, McClain MT, Rubertone MV, et al. Development of autoantibodies before the clinical onset of systematic lupus erythematosus. N Engl J Med. 2003;349(16):1526-1533.
Bruce Thiers, MD, FAAD, is a professor with the Department of Dermatology and Dermatologic Surgery at the Medical University of South Carolina in Charleston, SC.
