Tomoko Hiraiwa

Eosinophilic fasciitis with severe joint contracture in a patient with bladder cancer and B-cell lymphoma

has been reported. Our patient further developed hematological malignancy during the course. Dichloromethane and 1,2dichloropropane were carcinogenic, ink-removal agents used in the printing industry, that can cause cholangiocarcinoma, and we suspect that they were contained in the organic solvents used by our patient. This might have played a role in the occurrence of hematological malignancy. Eosinophilic fasciitis is sometimes associated with several autoimmune conditions, among which morphea is the most frequent but association with generalized morphea is rare. Furthermore, association with vitiligo and eosinophilic fasciitis is also rare, and only a few cases have been reported including vitiligo-like hypopigmentation. Whether hematological malignancy is associated with eosinophilic fasciitis or environmental factors is uncertain, however, our rare case demonstrates that diverse hematological as well as immunological manifestations can occur in association with eosinophilic fasciitis.

Hidradenitis suppurativa and multiple dermatofibromas in a patient with ulcerative colitis

1 Franchini M, Lippi G. Acquired factor VIII inhibitors. Blood 2008; 112: 250–255. 2 Franchini M, Gandini G, Di Paolantonio T, Mariani G. Acquired hemophilia A: a concise review. Am J Hematol 2005; 80: 55–63. 3 Merlini M, Moccia F, Delucchi M, Grillo G. Severe bleeding in a case of acquired factor VIII inhibitor associated with generalized pustular psoriasis. Ann Ital Med Int 2005; 20: 248–252. 4 Green D. Suppression of an antibody to factor VIII by a combination of factor VIII and cyclophosphamide. Blood 1971; 37: 381–387. 5 Di Minno MN, Iervolino S, Peluso R et al. Assessing joint involvement in haemophilia by clinical rheumatologic scores. A pilot study on similarities with subjects with psoriatic arthritis. Clin Rheumatol 2011; 30: 915–919.

Beneficial effect of hydroxychloroquine on cutaneous lupus erythematosus in a Japanese girl

the superficial dermis and subcutaneous tissue (Fig. 1c). The intraepidermal vesicles contained large numbers of lymphocytes. There was marked degeneration of keratinocytes and dyskeratotic cells in the epidermis (Fig. 1d) with exocytosis of lymphocytes into the epidermis and spongiosis (Fig. 1e). A positive phototest reaction occurred in 24 h after exposure to a single dose of UV-A radiation (4.8 J/cm) on the back (Fig. 1f). This reaction was negative in 48 h. The response to the minimal erythema dose of UV-B was normal. The skin lesions were not induced by a repetitive UV-A phototesting on the lower back (4.8 J/cm for 3 days). Therefore, hydroa vacciniforme was excluded and JSE was diagnosed. The eruption resolved with scarring within 6 weeks with application of betamethasone valerate 0.12% ointment (Fig. 1g,h). Juvenile spring eruption is considered to be a localized variant of polymorphic light eruption (PLE). The eruptions in JSE commonly resolve with minimal or no scarring within 2–3 weeks or less. Typically, the cell infiltrate is close to the epidermis, but does not show epidermotropism, and the epidermis shows mild changes with scattered apoptotic cells and some spongiosis. The clinical condition in our case was classified as severe and the eruption resolved with scarring. Histopathologically, the presence of epidermal apoptotic cell death, epidermotropism and large numbers of infiltrating lymphocytes corresponded to the severity of the clinical symptoms. Provocative phototesting was found to be positive in 38 of 68 PLE patients (56%), while it is commonly negative in JSE. Stratigos et al. reported a case of JSE with a positive phototest reaction to repetitive exposures of the affected site of the ears to UV-A for 3 consecutive days. Our case is the first report of JSE with a positive phototest reaction to a single UV-A exposure at a normal unaffected site. PLE shows a similar histological pattern of pernio. The subtle photosensitivity to UV-A and influence of non-freezing cold injuries might have been related to the disease severity. The pathogenesis of JSE is unclear and further accumulation of data is required.

Palmoplantar pustulosis with arthro‐osteitis triggered by recurrent appendeal abscess five years after appendectomy

Surg Pathol 1999; 23: 97–105. 3 Santa Cruz DJ, Aronberg J. Targetoid hemosiderotic hemangioma. J Am Acad Dermatol 1988; 19: 550–558. 4 Cotell S, Silverman A, Katta R. What is your diagnosis? Targetoid hemosiderotic hemangioma. Cutis 2003; 72: 51–52. 5 Chor PJ, Santa Cruz DJ. Kaposi’s sarcoma: a clinicopathologic review and differential diagnosis. J Cutan Pathol 1991; 19: 6–20. 6 Lowe L. Targetoid hemosiderotic hemangioma: selfassessment. J Cutan Pathol 1994; 21: 567–569. 7 Holden CA, Spittle MF. Angiosarcoma of the face and scalp, prognosis and treatment. Cancer 1987; 59: 1046–1057. 8 Morganroth GS, Tigelaar RE, Longley BJ, et al. Targetoid hemangioma associated with pregnancy and menstrual cycle. J Am Acad Dermatol 1995; 32: 282–284. 9 Rapini RP, Golitz LE. Targetoid hemosiderotic hemangioma. J Cutan Pathol 1990; 17: 233–235. 10 Mentzel T, Partanen TA, Kutzner H. Hobnail hemangioma (‘‘targetoid hemosiderotic hemangioma’’): clinicopathologic and immunohistochemical analysis of 62 cases. J Cutan Pathol 1999; 26: 279–286. 11 Franke FE, Steger K, Marks A, et al. Hobnail hemangiomas (targetoid hemosiderotic hemangiomas) are true lymphangiomas. J Cutan Pathol 2004; 31: 362–367.

Six cases of purpuric eruptions induced by epidermal growth factor receptor inhibitors

Erlotinib (Tarceva®) and gefitinib (Iressa®) are novel oral tyrosine kinase inhibitors targeting epidermal growth factor receptor (EGF-R). A number of skin reactions have been induced, however, purpuric eruption is rare. We report six cases of purpuric lesions some of which exhibited clinically mimicking HenochSchönlein purpura that occurred after treatment with EGF-R inhibitors for lung cancers. Two were men and four were women, and the mean age was 67.8 years (range: 60 to 80 year old). Clinical presentations are shown in Fig. 1, and the summary of cases is shown in Table 1. On physical examination, all cases had many small purpuric lesions with a diameter of 1-2 mm on the lower extremities, and trunk was also involved in one case. All of the cases were palpable purpura. Five cases had pustules in the center of purpuric lesions, and xerosis was observed in all cases. Erlotinib was thought to be the causative agent in three cases, two of them were switched from gefitinib to erlotinib, whereas other three cases were due to gefitinib. The duration ranged between 2 weeks and 6 months (mean: 2.9 months) after starting EGF-R inhibitors. Histopathological examination was performed in four cases, which revealed mild infiltrate of lymphocytes around the capillaries and extravasation of red blood cells in the upper dermis (Fig. 2), but there were no finding of leukocytoclastic vasculitis. Direct immunofluorescence was performed in one case, and there was no deposition of immunoglobulins. Skin eruptions were spontaneously improved by only interruption of the causative drugs, almost within 1 week. Platelet counts and coagulation profiles were within normal ranges in all cases. Four cases showed a favorable response to EGF-R inhibitors. By contrast, Letter to the Editor

Bone scintigraphy analysis of 44 cases of pustulotic arthro-osteitis associated with palmoplantar pustulosis

tor in the formation of psoriatic epidermal lesions. Next, we examined Th17 cells which are also required for development of psoriatic lesions, and found plenty of Th17 cells in both cases of PK (Fig. 1B). IL-17A is a key product of Th17 cells and it acts on keratinocytes to increase expression of several cytokines including chemokine (C-C motif) ligand (CCL)20, and psoriatic epidermis contains an abundant amount of CCL20. In the lesional thick epidermis of both PK and psoriatic cases, CCL20 expression was strongly upregulated and CC chemokine receptor (CCR)6 and CD3-double positive lymphocytes formed dermal clusters in the upper dermis of the lesional skin (Fig. 1C). Conversely, epidermal CCL20 expression and CCR6 and CD3-double positive lymphocyte dermal infiltration was downregulated in perilesional skin with thin epidermis as compared with lesional skin in PK cases (Fig. 1C). Interestingly, CCL20 expression was not downregulated and some CCR6 and CD3-double positive lymphocytes infiltration was seen in perilesional skin as well as in lesional skin in psoriatic cases. The CCL20/CCR6 chemokine system is crucial in psoriatic pathogenesis. In contrast, overexpression of CCL20 in keratinocytes may occur first in PK. Clonally proliferated keratinocytes with high CCL20 expression induce infiltration of CCR6-expressing Th17 cells only to the lesional skin, and activation of STAT3 plays an important role in psoriasiform epidermal hyperplasia in PK. CONFLICT OF INTEREST: None declared.

Recurrent pyoderma gangrenosum developed after a cesarean section with a 10-year interval

vitiligo-like leukoderma: an electron microscopic study. J Am Acad Dermatol 1983; 9: 696–708. 7 Hartmann A, Bedenk C, Keikavoussi P, et al. Vitiligo and melanoma-associated hypopigmentation (MAH): shared and discriminative features. J Dtsch Dermatol Ges J Ger Soc Dermatol 2008; 6: 1053–1059. 8 Lommerts JE, Teulings H-E, Ezzedine K, et al. Melanomaassociated leukoderma and vitiligo cannot be differentiated based on blinded assessment by experts in the field. J Am Acad Dermatol 2016; 75: 1198–1204. 9 Larsabal M, Marti A, Jacquemin C, et al. Vitiligo-like lesions occurring in patients receiving anti-programmed cell death-1 therapies are clinically and biologically distinct from vitiligo. J Am Acad Dermatol 2017; 76: 863–870.

Comorbidities of Japanese patients with palmoplantar pustulosis: a report from a single center

exposed sites, although they can occur on the whole body. EPA is asymptomatic and resolves spontaneously within 1–2 weeks. Skin biopsy shows dilated dermal blood vessels with plump endothelial cells, without vascular proliferation, and mild perivascular lymphocytic infiltrate in the upper dermis, as observed in the biopsy of our second patient. Most cases occur in immunocompetent patients, but there have been several reports in immunocompromised patients. Henry and Savasan reported a 13-year-old male on chemotherapy for Hodgkin lymphoma with doxorubicin, bleomycin, vincristine, etoposide, cyclophosphamide, and prednisone, who developed EPA. Neri et al. reported a 22-month-old girl who presented EPA at the time of the diagnosis of ALL. Both cases had a self-limited nature, similar to our patients. We believe either leukemia or chemotherapy could also be regarded as some of the triggering factors for the development of EPA. A clear relationship between EPA and these two factors has yet to be elucidated. Since viral infections were not ruled out in the first patient, the association with chemotherapy as a trigger cannot be established for both cases. Our cases, and others of EPA in immunocompromised patients, highlight the self-limited nature of the condition even in these hosts.

Non‐pigmented basal cell carcinoma occurring within a widespread vitiliginous lesion

Dear Editor, An 80-year-old man was referred to our department, complaining of a reddish ulcer on the face. He had been suffering from vitiligo on the face and trunk for 30 years, but had not received ultraviolet therapy. Before referral, biopsy of the ulcerative lesion was carried out at another clinic, and was diagnosed as basal cell carcinoma (BCC). Physical examination revealed a relatively well-circumscribed, 7 cm 9 6 mm ulcer on the vitiliginous skin on the left side of the nose (Fig. 1a). There was widespread depigmentation on the face, except for several spotty brownish patches. Examination by dermoscopy revealed arborizing vessels and superficial telangiectasia (Fig. 1b). The remaining tumor was surgically removed with a 3-mm margin and covered by a full-thickness skin graft. Histological features showed well-circumscribed basaloid and basosquamous tumor nests, calcification in the upper to lower dermis, and no overlying epidermis (Fig. 1c). The tumor cells were uniform in size with oval nuclei and scant cytoplasm, showing peripheral palisading, and were surrounded by myxomatous stroma (Fig. 1d). Solar degeneration was prominent in the upper dermis. Immunohistochemistry for HMB-45, MART-1 and Fontana– Masson showed negative findings in the overlying epidermis. There was no local recurrence or distant metastases during the 5-year follow-up period. Sun exposure is suggested to play a causative role in the development of BCC. There is a lack of melanocytes in vitiliginous lesions; therefore, it may be easily suspected that patients with vitiligo have an increased risk of developing skin cancers such as melanoma and non-melanoma. By contrast, reported cases of BCC on vitiliginous lesions are very few. In a cohort study of 477 patients with vitiligo, four patients developed BCC, only one of whom developed BCC on vitiliginous skin. The results showed that patients with vitiligo had a threefold lower probability of developing non-melanoma skin cancer. In another survey, among 1307 patients with vitiligo, two patients reported via questionnaire the occurrence of BCC in a vitiligo lesion. In a study examining more than 10 000 patients with vitiligo, the occurrence of non-melanoma skin cancer was 3.8%, compared with 19.6% in the control subjects. These studies suggest a decreased risk of non-melanoma skin cancer in patients with vitiligo. Among more than 300 BCC in our department over the past 10 years, there have been no other cases of BCC on vitiliginous lesions. The reason of the infrequency of non-melanoma skin cancers on vitiligo lesions is still unknown; however, several speculations have been proposed, such as an overexpression of the p53 tumor suppressor gene, overproduction of inflammatory cytokines that stimulate the production of superoxide dismutase and

Nail involvement associated with palmoplantar pustulosis

References 1 Barron SJ, Del Vecchio MT, Aronoff SC. Intravenous immunoglobulin in the treatment of Stevens-Johnson syndrome and toxic epidermal necrolysis: a meta-analysis with metaregression of observational studies. Int J Dermatol 2015; 54: 108–115. 2 Bastuji-Garin S, Fouchard N, Bertocchi M, et al. SCORTEN: a severity-of-illness score for toxic epidermal necrolysis. J Invest Dermatol 2000; 115: 149–153. 3 Roujeau JC, Bastuji-Garin S. Systematic review of treatments for Stevens-Johnson syndrome and toxic epidermal necrolysis using the SCORTEN score as a tool for evaluating mortality. Ther Adv Drug Saf 2011; 2: 87–94. 4 Huang YC, Li YC, Chen TJ. The efficacy of intravenous immunoglobulin for the treatment of toxic epidermal necrolysis: a systematic review and meta-analysis. Br J Dermatol 2012; 167: 424–432. 5 Lee HY, Lim YL, Thirumoorthy T, et al. The role of intravenous immunoglobulin in toxic epidermal necrolysis: a retrospective analysis of 64 patients managed in a specialized centre. Br J Dermatol 2013; 169: 1304–1309.