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site of healed herpes zoster,1 while Badri et al.2 reported a case of unilateral skin sarcoid reaction after homolateral mastectomy and lymphadenectomy for breast cancer. Both the articles gave us the opportunity to refer to the innovative concept of cutaneous immunocompromised district (ICD), i.e. a cutaneous site that once has been ‘scarred’ by prior clinical events (including chronic lymphedema, herpetic infection and neurological injuries,3–5 vaccination, thermal, or mechanical injuries, especially amputation), develops the propensity to host a secondary disease, which can appear after a variable time break (days to years).6 As underlined by Ghorpade, Wolf’s IR refers to the occurrence of a new disease at the site of healed herpetic infection.1,7 However, Wolf’s IR represents only a facet of the wider concept of ICD, which includes it, as already asserted by Ruocco et al.6 Badri et al.2 suppose that the cutaneous sarcoid reaction after mastectomy is caused by soluble tumoral antigens leading to a hypersensitivity reaction. Although interesting, this hypothesis seems to be not exhaustive in explaining this singular phenomenon. In fact, we think that lymph stasis following axillary lymphadenectomy for breast cancer might have been responsible for a consequent immune stasis, thus favoring the occurrence of sarcoid reaction strictly confined to that vulnerable area, which features a typical example of ICD. It is worth clarifying that the term immunocompromised generically indicates an alteration of the immune response and not necessarily a reduction of it.8 Depending on which neurotransmitters and immune cells are each time involved in the immune destabilization, this could be either defective and predispose to the outbreak of opportunistic tumors and infections (such as furuncle in the first report), or excessive and favor the occurrence of immunemediated diseases (such as sarcoid reaction in the second report). Through their brilliant observations, the authors of both articles gave us the opportunity to discuss such an intriguing topic. We think that the novel concept of ICD would be a good guidance for further investigations

Reply to: a rare case of vulvar skin metastasis of rectal cancer after operation

Editor, We appreciate the comments of Akpak et al. with regard to our manuscript on cutaneous scrotal metastasis1 and their interesting clinical observation of a woman who developed metastatic visceral malignancy to the vulva. What is truly fascinating is that the scrotum and the ª 2014 The International Society of Dermatology

aimed at clarifying the opportunistic localization of several cutaneous disorders. Vincenzo Piccolo MD Teresa Russo MD Adone Baroni MD, PhD Department of Dermatology and Venereology Second University of Naples Naples Italy E-mail: [email protected] Conflict of interest: No conflict of interest or financial disclosure is present. All authors had equally contributed. References 1 Ghorpade A. Wolf’s isotopic response manifesting as a furuncle on the forehead of an Indian man. Int J Dermatol 2013; 52: 119–120. 2 Badri T, Kerkeni N, Marrak H, et al. Unilateral upper limb skin sarcoid reaction after homolateral mastectomy for breast cancer. Int J Dermatol 2013; 52: 124–125. 3 Baroni A, Ruocco V, Di Maio R, et al. Papillomatosis cutis arising on an immuno-compromised district due to paraplegia. Br J Dermatol 2010; 163: 646–648. 4 Baroni A, Piccolo V, Russo T, et al. Recurrent blistering of the fingertips as a sign of carpal tunnel syndrome: an effect of nerve compression. Arch Dermatol 2012; 148: 545–546. 5 Piccolo V, Russo T, Baroni A. Unilateral bullous pemphigoid in hemiplegic patients: an instance of immunocompromised district. J Dermatol 2013; 40: 64–65. 6 Ruocco V, Brunetti G, Puca RV, et al. The immunocompromised district: a unifying concept for lymphoedematous, herpes-infected and otherwise damaged sites. J Eur Acad Dermatol Venereol 2009; 23: 1364– 1373. 7 Wolf R, Wolf D, Ruocco E, et al. Wolf’s isotopic response. Clin Dermatol 2011; 29: 237–240. 8 Ruocco V, Ruocco E, Brunetti G, et al. The correct meaning of the term immunocompromised: a necessary explanation. J Eur Acad Dermatol Venereol 2011; 25: 1242.

vulva are embryologically derived from the same origin.2 Between gestational weeks 4 and 7, both male and female embryos develop urogenital and labioscrotal folds. In males, these precursors develop into the urethra and scrotum, whereas in females they subsequently differentiate into the labia minora and labia majora.2 Metastasis of visceral malignancies to the scrotum is uncommon1 and hence, based on the similar embryologic derivation of the International Journal of Dermatology 2014, 53, e332–e346

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scrotum and the vulva, it would not be unexpected that the incidence of metastasis to the vulva might be similar to that to the scrotum. Indeed, vulvar metastases from visceral malignancies are rare; however, their incidence seems to be higher than that of scrotal metastases. Lerner et al.3 estimate that vulvar metastasis accounts for 5–8% of all vulvar malignancies. In 2003, Neto et al.4 reported 66 women treated at a single institution (the MD Anderson Cancer Center, Houston, TX, USA) over a period of 57 years who developed vulvar metastasis. Nearly half of the patients (46.9%) had a primary gynecologic tumor representative of cervical (22.7%), ovarian (12.1%), endometrial (9.1%), or vaginal (3.0%) cancer. The most common extragenital tumor site was the gastrointestinal tract (18.2%). In our review of cutaneous scrotal metastasis, we performed an extensive search of the literature available on PubMed and were able to identify only 29 men in whom recurrent visceral malignancy manifested with metastases to the scrotum.1 The most common sites of primary tumor were the prostate (27.6%) and gastrointestinal tract (27.6%), followed by the lung (13.8%). When gender-specific organs are excluded, gastrointestinal tumors are the most likely cancers to develop scrotal or vulvar metastases. The prognosis for patients who develop scrotal or vulvar metastases is poor. Neto et al. reported a median survival of just 7.5 months after the appearance of vulvar metastasis.4 Similarly, we found median survival to be only two months in men who developed scrotal metastases.1

The efficacy of 3% minoxidil vs. combined 3% minoxidil and Korean red ginseng in treating female pattern alopecia

Female pattern alopecia is a distressing condition that involves diffuse hair loss of the crown and frontal scalp. Thus far, no treatments specifically effective for female pattern alopecia are available, except minoxidil. Currently, the only FDA-approved treatment for female pattern alopecia is 2% topical minoxidil. It has been known for over 30 years that minoxidil stimulates hair growth, yet its mechanism of action on the hair follicle is very limited. Korean red ginseng (KRG) is a well-known herbal medication in Korea that has many biologic activities. The component of ginseng, known as ginsenoside, has been shown to accelerate neovascularization in burn wounds on the skin in mice.1 New vessel formation by saponin may affect hair growth by delivering oxygen and nutrients to the hair follicles. Kim et al.2 reported that KRG had a potent effect on the recovery of hair follicles International Journal of Dermatology 2014, 53, e332–e346

In conclusion, the appearance of a new skin lesion on either the scrotum or the vulva in a patient with a prior or current history of visceral malignancy should prompt the clinician to consider the possibility of cutaneous metastasis. Brian S. Hoyt, BSc Medical School University of Texas Medical School at Houston Houston TX, USA Philip R. Cohen, MD Department of Dermatology University of California San Diego San Diego CA, USA E-mail: [email protected] References 1 Hoyt BS, Cohen PR. Cutaneous scrotal metastasis: origins and clinical characteristics of visceral malignancies that metastasize to the scrotum. Int J Dermatol 2013; 52: 398– 403. 2 Yiee JH, Baskin LS. Penile embryology and anatomy. Scientific World J 2010; 10: 1174–1179. 3 Lerner LB, Andrews SJ, Gonzalez JL, et al. Vulvar metastases secondary to transitional cell carcinoma of the bladder. A case report. J Reprod Med 1999; 44: 729–732. 4 Neto AG, Deavers MT, Silva EG, et al. Metastatic tumors of the vulva: a clinicopathologic study of 66 cases. Am J Surg Pathol 2003; 27: 799–804.

through its combined effects on proliferation and apoptosis of cells in hair follicles in mice. Our previous study3 showed that KRG may be helpful in the treatment of androgenic alopecia in men. The present study was designed to comparatively analyze the effects of oral KRG in 41 patients with female pattern hair loss that were split into two groups, one using only topical 3% minoxidil (group 1, n = 21) and one using topical 3% minoxidil and oral KRG (group 2, n = 20). These two groups were evaluated before treatment, after 12 weeks, and after 24 weeks by phototrichogram (FolliscopeTM 2.5; LeadM Corp, Seoul, South Korea) and clinical photos (Fig. 1). KRG was taken as a capsule once a day that contained major ginsenoside-Rb1, 0.71 mg/g; Rb2, 0.26 mg/g; Rc, 0.28 mg/g; Rd, 0.06 mg/g; Re, 0.22 mg/g; Rf, 0.09 mg/g; Rg1, 0.36 mg/g; Rg2, 0.04 mg/g; Rg3, 0.02 mg/g; and other minor ginsenosides. The study protocol was approved by the institutional review board of the Korea University Ansan ª 2014 The International Society of Dermatology

Reply to: a rare case of vulvar skin metastasis of rectal cancer after operation.

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