15 March 2005

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2386 East Heritage Way, Suite B, Salt Lake City, Utah 84109 USA Phone +1-877-628-7300 • Email—[email protected] www.pachyonychia.org Letters to the Editor skin hypopigmentation despite similar mechanisms. One Seok Kweon YUN,1,3 Ki Hun SONG,1 explanation for the discrepancy relates to the degree of Su Ran HWANG,1 Han Uk KIM,1,3 Na Ri LEE,2,3 effect on various tissues to the target-specificity of imatinib Jin PARK1,3 5 because different tissues may have diverse c-kit isotypes. 1Departments of Dermatology, 2Internal Medicine, Chonbuk National Our patient showed graying of more than 50% of the scalp University Medical School, and 3Research Institute of Clinical Medicine of and pubic hair with generalized skin hypopigmentation, but Chonbuk National University, Biomedical Research Institute of Chonbuk the rest of the hairs were not involved. This may suggest National University Hospital, Jeonju, Korea that imatinib has target-specificity or a varying degree of c- kit inhibition not only between skin and hair but also doi: 10.1111/1346-8138.12342 between each hair. Besides hair graying, our patient also showed diffuse hair loss of the scalp, which is also a possi- REFERENCES ble side-effect of imatinib. It is associated with platelet- 1 Mariani S, Abruzzese E, Basciani S, Fiore D. Reversible hair depig- derived growth factor receptor (PDGFR)-regulated mainte- – 1 mentation in a patient treated with imatinib. Leuk Res 2010; 35: e64 nance of the anagen phase of the hair cycle. The hair loss e66. is thought to be related to inhibition of PDGFR by imatinib 2 Balagula Y, Pulitzer MP, Maki RG, Myskowski PL. Pigmentary with resulting telonization of the hair follicles that eventually changes in a patient treated with imatinib. J Drugs Dermatol 2011; led to telogen effluvium. 10: 1062. 3 Joensuu H, Trent JC, Reichardt P. Practical management of tyrosine Both hair graying and hair loss are stressful for young kinase inhibitor-associated side effects in GIST. Cancer Treat Rev female patients on antitumor therapy. Therefore, physicians 2011; 37:75–88. should be aware of hair graying as an additional possible side- 4 Etienne G, Cony-Makhoul P, Mahon F-X. Imatinib mesylate and gray effect of imatinib and notify patients. hair. N Engl J Med 2002; 347: 446. 5 Campbell T, Felsten L, Moore J. Disappearance of lentigines in a patient receiving imatinib treatment for familial gastrointestinal stro- CONFLICT OF INTEREST: None. mal tumor syndrome. Arc Dermatol 2009; 145: 1313.

Delayed-onset pachyonychia congenita caused by a novel mutation in the V2 domain of keratin 6b

Dear Editor, Pachyonychia congenita (PC) consists of a group of rare auto- (a) (b) somal-dominant ectodermal disorders characterized predomi- nantly by nail dystrophy. There are two main clinical subtypes of PC: PC-1 is caused by mutations in keratin 6a (K6a) gene or keratin 16 (K16) gene, accompanied by nail dystrophy, severe palmoplantar keratoderma and oral leukokeratosis; and PC-2 is linked to mutations in the keratin 6b (K6b) gene or keratin 17 (K17) gene, associated with nail dystrophy, focal palmoplantar (c) (d) keratoderma and multiple steatocysts.1 A 9-year-old Chinese female was affected by thickened fingernails and toenails at 6 years of age. Physical examination showed hyperkeratotic fingernails and toenails (Fig. 1a,b). Ste- atocystoma multiplex, palmoplantar keratoderma and natal teeth were not found in this patient. Repeated fungal examination under a microscope and culture excluded onychomycosis. There were no other family members affected by this disease. Figure 1. (a,b) Photograph of the thickened fingernails. (c) Following written informed consent, genomic DNA of the Direct sequencing of the k6b gene. A heterozygous missense proband, her parents, and 100 unrelated and unaffected peo- mutation 1495G?A (arrow), which predicts the amino acid ple was extracted from peripheral blood. Direct sequencing of change glycine to serine at codon 499 (G499S) was found. (d) DNA from the patient revealed a heterozygous 1495G?A Sequence in normal subjects.

Correspondence: Shengxiang Xiao, Ph.D. and Songmei Geng, Ph.D., Department of Dermatology, Second Afﬁliated Hospital of Xi’an Jiaotong University, 157 Xiwu Road, Xi’an, Shaanxi 0086-710004, China. Email: [email protected] and [email protected]

mutation in exon 9 of the K6b gene, in the tail domain, leading ACKNOWLEDGMENTS: We thank the patient and her family to the substitution of glycine 499 by serine (G499S; Fig. 1c). for their participation in this report. The authors declare that there was No mutations were found in K17, K16, K6a or K6c. No such no funding. mutation was found in her parents and the 100 unrelated controls (Fig. 1d). Three mutations have been reported in K6b, but this is the CONFLICT OF INTEREST: The authors have no conflict of first mutation to be reported in the tail domain of PC-2. interest to declare. Another known similar mutation was a insertion mutation 2 located in the tail domain of K6a in PC-1. Unlike epidermolysis Kun GUO, Shengxiang XIAO, Songmei GENG, bullosa simplex, the correlation between severity of disease Yiguo FENG, Dingwei ZHANG, Pengjun ZHOU, and the location of the mutation within the keratin molecule of Yanfei ZHANG PC is not clear. Connors et al.3 detected a case of late-onset Department of Dermatology, The Second Affiliated Hospital of Xi’an Jiaotong PC association with a mutation K354N in the central 2B University, Xi’an, China domain of K16. Our group has reported a mutation N109D in the second half of the 1A domain of K17 with delayed onset doi: 10.1111/1346-8138.12349 PC-2.4 Terrinoni et al.5 reported a postzygotic mutation in the V1 domain of K16 with unilateral palmoplantar nevus and REFERENCES delayed onset PC-1. In this report, we found a mutation in the V2 domain of K6b associated with late onset and milder thick- 1 Vishakha MS, Sarah LS. A novel mutation in K6b in pachyonychia ened nails. The patients listed above had delayed-onset PC, congenita type 2. J Invest Dermatol 2007; 127: 2060–2062. 2 Wilson NJ, Leachman SA, Hansen CD et al. A large mutational study the milder phenotypes, and their mutation located at the less in pachyonychia congenita. J Invest Dermatol 2011; 131: 1018–1024. critical site of the keratins which is consistent with Connors 3 Connors JB, Rahil AK, Smith FJD, Mclean WHI, Milstone LM. et al. and Xiao et al.’s speculation.3,4 Delayed onset pachyonychia congenita associated with a novel In conclusion, we reported a Chinese female affected with mutation in the central 2B domain of keratin 16. Br J Dermatol 2001; – delayed-onset PC-2 caused by a novel mutation in the K6b 144: 1058 1062. 4 Xiao SX, Feng YG, Ren XR et al. A Novel mutation in the second half of V2 domain. The more PC patients that are reported, the more the keratin 17 1A domain in a large pedigree with delayed-onset pachy- clinical data is accumulated. It will help expand the under- onychia congenita type 2. J Invest Dermatol 2004; 122: 892–895. standing of relationship between genotype and phenotype in 5 Terrinoni A, Puddu P, Didona B et al. A mutation in the V1 domain of PC and may give some clues to the cause of the phenotypic K16 is responsible for unilateral palmoplantar verrucous nevus. J Invest Dermatol 2000; 114: 1136–1140. variability.

Generalized granuloma annulare after bacillus Calmette– Guerin vaccination, clinically resembling papular tuberculid

Dear Editor, history including tuberculosis. He received a BCG vaccination The bacillus Calmette–Guerin (BCG) vaccine contains a live, on his right arm 1 month after birth. He presented multiple attenuated strain of bovine tuberculin bacteria Mycobacterium small erythematous papules, plaques and crusts on the face, bovis. BCG vaccination has appeared to protect young chil- trunk and extremities symmetrically without symptoms occur- dren from more serious forms of tuberculosis. Real incidence ring 7 weeks after BCG vaccination. The BCG injection site of complications caused by BCG vaccination have been diffi- also showed papular lesions (Fig. 1a–c). On physical examina- cult to ascertain, but are extremely low in spite of the great tion, no abnormal lymphadenopathy was seen and the overall number of vaccinations performed. Skin complications vary clinical features were similar to popular tuberculid. Routine from local reactions to disseminated BCG infections.1 Herein, blood and biochemical tests as well as chest X-ray did not we report a 3-month-old boy with a complication of general- show any abnormal findings. QuantiFERON-TB Gold using ized granuloma annulare (GGA) mimicking papular tuberculid serum and tuberculin skin test with purified protein derivative after BCG vaccination. of tuberculin were negative. Histopathology showed a feature A 3-month-old boy was referred to our dermatology clinic of chronic palisading granulomatous inflammation with central because of generalized eruptions after BCG vaccination. The necrosis and suppuration(Fig. 1d,e). Multiple foci of inflamma- boy was a full-term baby and had no specific past and family tion with a central core of collagen degeneration surrounded

Correspondence: Eung Ho Choi, M.D., Ph.D., Department of Dermatology, Yonsei University Wonju College of Medicine, 162 Ilsan-dong, Wonju 220-701, Korea. Email: [email protected]