A Case of Eczematoid Graft‐Versus‐Host Disease

A 13‐year‐old boy underwent allogeneic hematopoietic stem cell transplantation (HSCT) for underlying acute lymphoblastic leukemia and achieved neutrophil engraftment 28 days after HSCT. He developed ichthyosis 6 weeks after HSCT and then keratotic follicular papules, palmoplantar keratoderma, and a seborrheic dermatitis–like eruption 18 weeks after HSCT. From skin biopsies he was diagnosed with eczematoid graft‐versus host disease (GVHD), which showed spongiosis with scattered necrotic keratinocytes. He responded to oral and topical steroids and an increase in cyclosporine dose. Although uncommon, eczematoid GVHD must be considered in children who have undergone HSCT and then develop an atypical eczematous eruption, especially in the absence of a history of atopy.     

Eosinophilic pustular folliculitis: A published work‐based comprehensive analysis of therapeutic responsiveness

Eosinophilic pustular folliculitis (EPF) is a non‐infectious inflammatory dermatosis of unknown etiology that principally affects the hair follicles. There are three variants of EPF: (i) classic EPF; (ii) immunosuppression‐associated EPF, which is subdivided into HIV‐associated (IS/HIV) and non‐HIV‐associated (IS/non‐HIV); and (iii) infancy‐associated EPF. Oral indomethacin is efficacious, especially for classic EPF. No comprehensive information on the efficacies of other medical management regimens is currently available. In this study, we surveyed regimens for EPF that were described in articles published between 1965 and 2013. In total, there were 1171 regimens; 874, 137, 45 and 115 of which were applied to classic, IS/HIV, IS/non‐HIV and infancy‐associated EPF, respectively. Classic EPF was preferentially treated with oral indomethacin with efficacy of 84% whereas topical steroids were preferred for IS/HIV, IS/non‐HIV and infancy‐associated EPF with efficacy of 47%, 73% and 82%, respectively. Other regimens such as oral Sairei‐to (a Chinese–Japanese herbal medicine), diaminodiphenyl sulfone, cyclosporin and topical tacrolimus were effective for indomethacin‐resistant cases. Although the preclusion of direct comparison among cases was one limitation, this study provides a dataset that is applicable to the construction of therapeutic algorithms for EPF.     

HSV‐associated erythema multiforme in a patient after hematopoietic stem cell transplantation

Herpes simplex virus (HSV)–associated erythema multiforme (HAEM) is an acute and self‐limiting mucocutaneous hypersensitivity reaction triggered by herpes virus infections. We reported a patient with HAEM after hematopoietic stem cell transplantation (HSCT). A 55‐year‐old man received HSCT 7 months ago. He suffered from chronic graft versus host disease 4 months after HSCT and was treated with prednisone and tacrolimus. One week ago, he developed generalized macules with leukopenia. Dermatological examination revealed multiple iris‐like erythemas on his trunk and extremities. The skin lesions and leukopenia resolved upon anti‐HSV treatment.     

Nailfold capillary abnormalities are prevalent in sclerodermoid graft‐versus‐host disease and readily detected with dermatoscopy

Background Well‐recognized videocapillaroscopic patterns have been described in systemic sclerosis (SS). However, no studies have described the capillary abnormalities of sclerodermoid chronic graft‐versus‐host disease (Scl GVHD) developed after allogeneic haematopoietic stem cell transplantation (allo‐HSCT). Objectives The aims of this study were to find the characteristics of nailfold capillary changes in Scl GVHD after allo‐HSCT. Patients and methods Eighteen patients affected by Scl GVHD and a control group of 15 patients with lichenoid GVHD were evaluated. Duration and type of sclerodermoid GVHD, Raynaud phenomenon (RP), dysphagia, joint contractures, antinuclear antibodies (ANA), anti‐Scl‐70 and anticentromere (ACA) antibodies were investigated parameters. A nailfold capillary examination using a standard dermatoscope was performed on all fingers of each subject. Results Twelve patients were male and six were female with a mean age of 37 ± 11·6 years. Joint retractions and dysphagia developed in 27·8% and 38·9% of the patients, respectively. Three (16·7%) patients had RP. Autoimmune markers like anti‐Scl‐70 and ACA were negative in all. Capillaroscopy was abnormal in 15 patients with Scl GVHD. A regular disposition of the capillary loops along with avascular whitish linear areas at the level of the last row, neovascularization with reticular pattern, capillary disorganization, haemorrhages, enlarged capillaries and avascular areas were the main features. No capillary abnormalities were observed in patients with lichenoid GVHD. There was no statistically significant correlation between ANA positivity, RP, joint retractions, dysphagia, extensiveness of Scl GVHD, duration of sclerodermoid lesions and nailfold capillaroscopy analysis. Conclusions This study shows the identification of distinct nailfold capillaroscopy patterns in patients with Scl GVHD but it does not confer special risk for any other specific clinical symptoms of the disease.     

Hematopoietic stem cell transplantation for cutaneous T‐cell lymphoma: Summary of 11 cases from two facilities in Japan and Brazil

Some patients with cutaneous T‐cell lymphoma (CTCL) show a miserable clinical course and the only option that can induce long‐term remission for advanced CTCL may be hematopoietic stem cell transplantation (HSCT). So far, studies on HSCT for CTCL patients have been limited. In this study, we summarized 11 cases with CTCL treated with HSCT, including nine cases in Japan and two cases in Brazil. The patients were five cases with mycosis fungoides (MF), two cases with Sézary syndrome (SS), three cases with anaplastic large cell lymphoma, and one case with primary cutaneous peripheral T‐cell lymphoma, not otherwise specified (PTL‐NOS). Currently, seven out of 11 cases are alive (at 13–108 months after transplantation) and four died at 15 days to 14 months after transplantation. When focusing on the eight patients who received allogeneic HSCT for MF/SS and PTL‐NOS, all four patients at 45 years old or under are alive at present. One case showed relapse in the skin. On the other hand, one out of the other four patients at over 45 years old survived. Engraftment failure was seen in one case and all the other three cases experienced relapse. Although this is only a case series with a small number, our study has suggested that we should be careful about age when treating patients with MF/SS by allogeneic HSCT.     

Facial pustules due to drug‐induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms may histopathologically mimic eosinophilic pustular folliculitis: A case report

Pustules with facial and/or neck edema is one characteristic feature of drug‐induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DIHS/DRESS) at the early stage. Although several retrospective histopathologic studies on DIHS/DRESS have been reported, the detailed histopathologic findings of facial pustules for DIHS/DRESS are unavailable. We herein report a case of DIHS/DRESS with facial pustules that was histopathologically similar to eosinophilic pustular folliculitis (EPF). Eosinophilic infiltration into expanded follicles and sebaceous glands, which is highly characteristic of EPF, was detected in pustules due to DIHS/DRESS in this case. There are numerous pathophysiological similarities between DIHS/DRESS and EPF, which may cause their histopathologic similarity. Our findings suggest that facial pustules of DIHS/DRESS may histopathologically mimic EPF.     

Eosinophilic pustular folliculitis: A review of the Japanese published works

Eosinophilic pustular folliculitis (EPF), also known as Ofuji's disease, is an inflammatory dermatosis that was first described in Japan in 1970. More than 300 cases have been reported so far, and 113 Japanese cases have been reported in Japan since 1980. To comprehend the characteristics of Japanese EPF cases, we classified these cases into three types: classic, immunosuppression‐associated (IS‐EPF), and infancy‐associated (I‐EPF). Trends in age of onset and in distribution and characterization of eruptions differed between the types. We found 91 cases of classic EPF (mean age, 39.7 years), consisting of 66 males (73%) and 25 females (27%), in most of which eruptions primarily affected the face; 18 cases of IS‐EPF (44.2 years), consisting of 15 males (83%) and three females (17%), in which eruptions affected the face less predominantly; and four cases of I‐EPF (7.0 years), consisting of two males (50%) and two females (50%), primarily affecting the scalp. The number of IS‐EPF cases has increased since the late 1990s, reflecting the increasing number of HIV‐positive patients in Japan. Systemic non‐steroidal anti‐inflammatory drugs were effective in more than 70% of cases. Dimethyl diphenyl sulfone, antibiotics including minocycline, psoralen plus ultraviolet A therapy and ultraviolet B treatments worked in some cases. Topical steroids and tacrolimus were also effective in some cases of EPF, while topical indomethacin was less effective.     

Eosinophilic pustular folliculitis: The transition in sex differences and interracial characteristics between 1965 and 2013

Eosinophilic pustular folliculitis (EPF) is characterized by a non‐infectious infiltration of eosinophils in the hair follicles. It has three variants: (i) classic EPF; (ii) immunosuppression‐associated EPF, which herein is subdivided into HIV‐associated (IS/HIV) and non‐HIV‐associated (IS/non‐HIV); and (iii) infancy‐associated EPF (I‐EPF). The rarity of EPF has hindered our understanding of this entity. To examine the characteristics of EPF, with respect to age, sex, race, and chronology, published in case reports to date, we queried PubMed using the following terms: (“eosinophilic pustular folliculitis” [All Fields] OR “eosinophilic folliculitis” [All Fields]) AND (“1965/1/1” [PDAT]: “2013/12/31” [PDAT]). Additional Japanese cases were collected from Igaku Chuo Zasshi through Ichushi‐Web, JDream III, and secondhand quotations from domestic periodicals published in Japan. Proceedings were excluded. The PubMed search produced 275 citations containing 358 cases of EPF (224 men, 132 women, and two of unspecified sex); these cases involved classic EPF (101 Japanese and 81 non‐Japanese), IS/HIV (4 Japanese and 85 non‐Japanese), IS/non‐HIV (4 Japanese and 20 non‐Japanese), and I‐EPF (4 Japanese and 59 non‐Japanese). Ichushi generated an additional 148 citations containing 207 cases of Japanese (148 men and 59 women), which included cases of classic EPF (181 cases), IS/HIV (14 cases), IS/non‐HIV (9 cases), and I‐EPF (3 cases). There was no sex difference in the classic EPF cases reported between 2003 and 2013, whereas IS/HIV, IS/non‐HIV, and I‐EPF were predominated by men. There is room for reconsideration of sex differences, particularly with regard to classic EPF. The rarity and specificity of I‐EPF in Japan may reflect a state of uncertainty about this entity.     

Hematopoietic stem cell transplantation in advanced cutaneous T‐cell lymphoma

We retrospectively reviewed data pertaining to five patients with cutaneous T‐cell lymphoma (CTCL) who had received hematopoietic stem cell transplantation (HSCT) between 2004 and 2015 at Kurume University Hospital, along with their clinical data until March 2016. For patients with advanced CTCL eligible for HSCT, autologous HSCT was performed when they responded well to chemotherapy, and allogeneic HSCT was selected for patients with advanced mycosis fungoides (MF)/Sézary syndrome (SS) and CTCL other than MF/SS with poor chemosensitivity. Two patients (primary cutaneous anaplastic large cell lymphoma and primary cutaneous CD8⁺ aggressive epidermotropic cytotoxic T‐cell lymphoma) who responded well to chemotherapy received autologous HSCT: one patient was alive in partial remission and the other died due to therapy‐related acute myeloid leukemia without disease relapse. In the remaining three patients with MF or SS, allogeneic HSCT was performed. Although one patient with MF died due to disease progression, the remaining two patients were alive in complete remission. Although there were two deaths in this study, the outcomes were considered satisfactory.     

Eosinophilic pustular folliculitis: A proposal of diagnostic and therapeutic algorithms

Eosinophilic pustular folliculitis (EPF) is a sterile inflammatory dermatosis of unknown etiology. In addition to classic EPF, which affects otherwise healthy individuals, an immunocompromised state can cause immunosuppression‐associated EPF (IS‐EPF), which may be referred to dermatologists in inpatient services for assessments. Infancy‐associated EPF (I‐EPF) is the least characterized subtype, being observed mainly in non‐Japanese infants. Diagnosis of EPF is challenging because its lesions mimic those of other common diseases, such as acne and dermatomycosis. Furthermore, there is no consensus regarding the treatment for each subtype of EPF. Here, we created procedure algorithms that facilitate the diagnosis and selection of therapeutic options on the basis of published work available in the public domain. Our diagnostic algorithm comprised a simple flowchart to direct physicians toward proper diagnosis. Recommended regimens were summarized in an easy‐to‐comprehend therapeutic algorithm for each subtype of EPF. These algorithms would facilitate the diagnostic and therapeutic procedure of EPF.     

A question of persistence: Langerhans cells and graft‐versus‐host disease

Langerhans cells (LCs) have been scrutinized many times in studies of the pathogenesis of graft‐versus‐host disease (GVHD). As migratory dendritic cells, LCs are capable of direct antigen presentation to cytotoxic T cells. Their self‐renewal capacity has led to speculation that persistent recipient LCs could provide a continuous source of host antigen to donor T cells infused during hematopoietic stem cell transplantation (HSCT). In this issue of Experimental Dermatology, a new study examines at the relationship between recipient LCs and chronic GVHD.     

Extracorporeal photopheresis in graft‐versus‐host disease

Graft‐versus‐host disease (GvHD) is a common and often serious complication of hematopoietic stem cell transplantation. There are two major forms of GvHD: an acute form which develops in the first 100days after HSCT, and a chronic form which develops later. Chronic GvHD is a multiorgan syndrome with many features of autoimmune diseases, such as sclerodermatous skin changes, cholestasis, pulmonary fibrosis, xerostomia, oral ulcerations, myositis and fasci‐itis. Unlike acute GvHD which is characterized by acute alloreactivity,the etiology of chronic GvHD is controversial and is believed to be either an extension of acute GvHD and/or a result of dysfunctional immune reconstitution with generation of autoantibodies and autoreactive T‐cell clones. GvHD is usually treated with corticosteroids and other immunosuppressants which do not always succeed in arresting its evolution. Extracorporeal photochemotherapy has been used in patients with both acute and chronic GvHD.     

Eosinophilic pustular folliculitis associated with hematological disorders: A report of two cases and review of Japanese literature

Eosinophilic pustular folliculitis (EPF) occurs in patients with hematological disorders. However, clinical information about hematological disorder‐associated EPF is scarce. We report two cases of EPF associated with mantle cell lymphoma and reviewed the available published work on Japanese cases. We identified a total of 23 Japanese cases, including the two cases reported here, who had hematological disorder‐associated EPF. Fourteen cases were associated with treatment for hematological malignancies (transplantation‐related EPF) and nine cases were associated with hematological malignancies themselves (hematological malignancy‐related EPF). Although the skin eruption was clinically indistinguishable between the two subtypes, transplantation‐related EPF occurred on the face and trunk of young and middle‐aged men and women, whereas hematological malignancy‐related EPF occurred mostly on the face of older men. Peripheral blood eosinophilia was more frequently observed in transplantation‐related EPF. These observations suggest variations among patients with EPF associated with hematological disorders.     

Eosinophilic pustular folliculitis following autologous peripheral blood stem-cell transplantation

We describe a case of eosinophilic pustular folliculitis (EPF) occurring after autologous peripheral blood stem-cell transplantation for non-Hodgkin's lymphoma and successfully treated with oral and topical indomethacin. Including ours, the reported cases of EPF with HIV-negative hematological disease have shown clinical features similar to those of HIV-associated EPF, however the prognosis is better than that for HIV-associated EPF, which usually shows a persistent course. EPF with HIV-negative hematological disease can be classified as a unique group in EPF.     

Clinical and histopathological differential diagnosis of eosinophilic pustular folliculitis

Eosinophilic pustular folliculitis (EPF) is an inflammatory disease characterized by repeated pruritic follicular papules and pustules arranged in arcuate plaques, and folliculotropic infiltration of eosinophils. The diagnosis of EPF is occasionally difficult and problematic because EPF may share the clinical appearance and histological findings with other diseases. Moreover, EPF has several clinical subtypes, including the classical type, infantile type and immunosuppression‐associated type. Because the therapies of EPF are relatively specific as compared to eczematous disorders, accurate diagnosis is essential for the management of EPF. Clinical differential diagnoses include tinea, acne, rosacea, eczematous dermatitis, granuloma faciale, autoimmune annular erythema, infestations and pustular dermatosis. Histologically, cutaneous diseases with eosinophilic infiltrates can be differentially diagnosed. Follicular mucinosis, mycosis fungoides and other cutaneous T‐cell lymphomas are the most important differential diagnoses both clinically and histopathologically. It should be kept in mind particularly that the initial lesions of cutaneous T‐cell lymphoma resemble EPF.     

Neuroblastoma‐like schwannoma with giant rosette: A potential diagnostic pitfall for hyalinizing spindle cell tumor

Neuroblastoma‐like schwannoma (NLS) is a rare variant of a common tumor. The aim of this study is to discuss, through a literature review, the differential diagnoses of NLS while emphasizing the importance of ancillary studies. So far, 24 cases have been reported. We describe an additional case in a 64‐year‐old woman who had a 3‐cm subcutaneous tumor on her flank. The histological examination showed an encapsulated neoplasm. Most of the tumor was made of giant rosettes. These rosettes had several sizes reaching 2.6 mm. They showed a palisade of rounded cells. Nuclei were hyperchromatic but bland. The center was made of eosinophilic cores of collagenous radiating fibrils. Neoplastic cells stained strongly for S‐100 protein. In the capsule, perineural cells stained for epithelial membrane antigen (EMA). No expression of Mucin 4 (MUC4) was present. This was consistent with NLS. The same peculiar appearance of giant rosettes has been described in hyalinizing spindle cell tumor with giant rosettes (HSCT). We propose the term “neuroblastoma‐like schwannoma” when there are small rosettes, “HSCT‐like schwannoma” for tumors with giant rosettes and “collagen‐rich schwannoma” when there are “ill‐defined” structures reminiscent of rosettes. Immunohistochemical panel containing S100, EMA, and MUC4, as well as molecular testing when needed should be performed.     

Severe cutaneous bacillus Calmette–Guérin infection in immunocompromised children: the relevance of skin biopsy

Disseminated bacillus Calmette‐Guérin infection (BCGitis) is an uncommon condition which is usually associated with primary immunodeficiency. Skin histopathology findings have been described in rare cases only. A retrospective clinicopathological study was performed to assess the potential utility of skin biopsies in the diagnosis, prognosis and follow‐up of these patients. Four cases of disseminated BCGitis in children with Severe Combined ImmunoDeficiency were biopsied before and after Haematopoietic Stem Cell Transplantation (HSCT). The results were compared to the clinical and immunological status of the children. Early skin biopsies revealed either dense dermal infiltration by foamy macrophages filled with acid fast bacilli (AFB) or mycobacterial spindle‐cell pseudotumors rich in AFB. There were no granulomas. These patterns led to the diagnosis of disseminated BCGitis potentially caused by severe immunodeficiency. After HSCT, repeated skin biopsies were performed on persistent or new cutaneous lesions to rule out immune reconstitution inflammatory syndrome and to check for tuberculoid granulomas. One patient died of BCGitis combined with graft versus host disease. The 3 others presented with progressive‐onset well differentiated granulomas over a long period and recovered. Skin biopsy is a useful part of the diagnostic workup for disseminated BCGitis, directing the clinician toward severe immunodeficiency. Moreover, skin biopsy may be a useful means of monitoring immune restoration for prognostic purposes.     

Eosinophilic pustule smear in the diagnosis of pediatric post-transplant eosinophilic folliculitis

Hematologic-associated eosinophilic pustular folliculitis is a subtype of eosinophilic pustular folliculitis (EPF) which develops in patients with underlying hematological malignancies after treatment with chemotherapy, bone marrow transplant (BMT), or stem cell transplant (SCT). Few cases of hematological-associated EPF have been reported in pediatric patients. Skin biopsy is considered the gold standard for diagnosis. We describe a case in which Wright staining of a pustule smear for eosinophils provided data to rapidly support a clinical diagnosis of hematologic-associated EPF.