Hideki Mukai

Lymphocutaneous type of nocardiosis caused by Nocardia brasiliensis : A case report and review of primary cutaneous nocardiosis caused by N. brasiliensis reported in Japan

Nocardiosis is a mixed suppurative and granulomatous inflammatory disease caused by infection with Nocardia organisms, a group of aerobic actinomycetes. We recently encountered a 25‐year‐old woman with posttraumatic nocardiosis of the lower extremities. The clinical symptoms noted during her first visit included erythematous swelling of the right knee accompanied by white maceration of the center of the knee and erosions, shallow ulcers and satellite pustules. In addition, multiple erythematous areas (up to the size of the tip of the thumb) were linearly distributed on the right thigh. These lesions were painful, and right inguinal lymphadenopathy was also noted. No lesion was found in internal organs such as the lungs. Histopathologically, signs of nonspecific granulomatous inflammation were observed, as well as several filamentous branching bacilli positive on Grocott stain. The organisms isolated from culture of pus were acid‐fast, Gram‐positive long rods. The isolated strain was finally identified as Nocardia brasiliensis. The patient was therefore diagnosed with lymphocutaneous type of primary cutaneous nocardiosis caused by N. brasiliensis. Drip infusion of flomoxef sodium was initially performed to treat her condition. Because of exacerbation of erythematous swelling of the right knee and an increase in number of pustules, treatment was switched to oral minocycline hydrochloride therapy. The disease healed 9 weeks after the start of oral minocycline hydrochloride therapy. Our patient was free of systemic immunosuppression and was neither under 10 nor over 65 years of age. She may therefore be considered a rare case of lymphocutaneous type of nocardiosis. We present this case and discuss reported cases of primary cutaneous nocardiosis due to N. brasiliensis in Japan.

Cutaneous endometriosis in the umbilical region: The usefulness of CD10 in identifying the interstitium of ectopic endometriosis

Endometriosis is a condition in which endometrium or endometrium‐like tissue grows in areas other than the endometrium and is often found within the pelvis such as in the uterus or ovary, but occasionally develops ectopically in the skin. In this paper, we report a case of cutaneous endometriosis in the umbilical region found in a 37‐year‐old woman with no history of pregnancy. The lesion was a brown, firm and elastic nodule, 9 mm × 7 mm in size, and caused bleeding as well as pain which increased during menstruation. Histopathological findings revealed that there were small and large glandular cavity structures in the dermis and the edematous interstitium around it. On immunohistochemical staining for estrogen and progesterone receptors, the cellular nuclei of glandular cavity walls were mainly found to be positive for both, and cells in the edematous interstitium around the glandular cavity were positive for CD10. Consequently, we diagnosed this case as cutaneous endometriosis in the umbilical region. CD10 was initially described as a tumor‐specific antigen found in acute lymphoblastic leukemia. Recently, the usefulness of CD10 in diagnosing endometriosis in addition to various types of lymphoma or blood cancer has been confirmed, and in our case it also proved to be as useful as estrogen receptor or progesterone receptor in the definitive diagnosis of endometriosis.

Zosteriform skin involvement of nodal T‐cell lymphoma: A review of the published work of cutaneous malignancies mimicking herpes zoster

A 77‐year‐old Japanese woman initially presented with non‐Hodgkins lymphoma involving her neck, axillary and inguen lymph nodes. She had edematous erythema and nodules limited to the skin in zosteriform distribution on the left side chest wall along the T4–5 dermatome. In addition, since 1970, we have mainly been collecting English‐language articles on malignant skin tumors and skin metastasis described as zosteriform in the title, and we have reviewed a total of 29 cases, including our own. It should be mentioned that 59% of the cases reported had been diagnosed with herpes zoster at the time of the initial examination and that many of them had received drug therapy (e.g. acyclovir). We wish to add the dermatomic eruption mimicking zoster sine herpete to the list of possible presentations of cutaneous malignancies.

Efficacy of inpatient treatment for atopic dermatitis evaluated by changes in serum cortisol levels.

When dealing with patients with severe atopic dermatitis (AD), inpatient treatment is useful for alleviating skin symptoms in short periods of time. We previously found that many severe AD patients had low serum cortisol levels at admission. The present study was undertaken to evaluate the efficacy of inpatient treatment in 29 adults with AD through comparisons of serum cortisol, plasma adrenocorticotropic hormone (ACTH), serum thymus and activation‐regulated chemokine (TARC), and serum lactate dehydrogenase (LDH) levels at admission with those at the time of discharge. Serum cortisol and plasma ACTH levels were significantly higher at discharge. On the other hand, serum TARC and serum LDH were significantly lower at discharge. We examined whether the suppression of hypothalamic–pituitary–adrenocortical function that was seen at admission was attributable to disturbed circadian rhythms due to sleep disorders by analyzing hypothalamic–pituitary–adrenocortical function in relation to the presence/absence of sleep disorders, serum cortisol levels and daily urinary free cortisol. Of the 17 patients with low serum cortisol levels upon admission, 15 (88.2%) had sleep disorders upon admission. However, the daily urinary free cortisol increased significantly from 8.0 ± 5.5 μg/day (at admission) to 18.5 ± 17.2 μg/day (at discharge). These results suggested that the suppression of endocrine function seen at admission was not attributable to disturbed circadian rhythms due to sleep disorders but represented true suppression of the endocrine system. These results indicated that inpatient care was useful for treating patients with severe AD, enabling efficient improvement of the skin condition and recovery from suppressed endocrine function.

Cutaneous myeloid sarcoma presenting as grey pigmented macules.

According to previous reports, cutaneous myeloid sar-coma often manifests as a red nodule on the skin. We report here a patient with cutaneous myeloid sarcoma presenting with a unique skin lesion. A 71-year-old man presented with pigmented macules of one month duration. Physical examination showed multiple grey pigmented macules, 10–30 mm in diameter , on the face and trunk (Fig. 1a). His white blood cell count was 2.3 × 10 9 /l, with 8.5% blast cells, 1.0% myeloid cells, 3.5% stab cells, 23.0% segmented neu-trophils, 56.0% lymphocytes, 6.5% monocytes, 0.5% eosinophils, and 0.5% basophils. His platelet count was 7.2 × 10 9 /l, red blood cell count 3.75 × 10 12 /l, and haemoglobin level 10.3 g/dl. Other routine biochemical tests and urinalysis were normal. Microscopic examination showed sheets of cells with abundant eosinophilic cytoplasm, enlarged, frequently reniform, nuclei, and numerous mitotic figures (Fig. 1b). Immunohistoche-mical studies were positive for CD43, CD45, myelo-peroxidase, and lysozyme, and negative for CD3, CD4, CD8, CD20, and CD56, confirming the diagnosis of myeloid sarcoma. When examined at the department of haematology at our request, the patient was diagnosed as having acute myeloid leukaemia with the 7;21 trans-location. On the basis of this diagnosis, the patient was administered induction chemotherapy with intravenous enocitabine and aclarubicin hydrochloride. The macu-les promptly disappeared with this treatment. After 3 courses of chemotherapy, the patient was in complete clinical remission and remained disease-free during a follow-up period of 18 months. DISCUSSION The cutaneous manifestations of leukaemia can be non-specific (containing no leukemic cells), e.g. panni-culitis and generalized pruritus; or specific (leukaemia cutis). Non-specific lesions are found in up to 30% of leukaemia patients (1), but leukaemia cutis is much less common. Skin involvement is usually a late occurrence, and leukaemia cutis preceding marrow or peripheral blood abnormality is extremely rare (2). The clinical manifestations of leukaemia cutis are variable, including macules, nodules, purpura, and erythroderma, and the condition often resembles cutaneous lymphoma. Myeloid sarcoma is an extramedullary tumour of immature cells of granulocytic series, generally occurring in approximately 2% of patients with acute myeloid leukaemia (3). Myeloid sarcoma occurs mostly in adults aged 45–55 years, and it has a predilection for the bone, soft tissue, and skin (4), but they have been found in many other organs, including the abdominal organs, testis, and lacrimal gland. The skin lesions most commonly occur on the trunk, scalp and face. In general, they …

Multiple primary syphilis on the lip, nipple-areola and penis: An immunohistochemical examination of Treponema pallidum localization using an anti-T. pallidum antibody.

Primary syphilis caused by Treponema pallidum usually develops after sexual contact as an initial solitary sclerosis or hard chancre in the genital region. We describe a case of primary syphilis at three sites in genital and extragenital regions of a man who had sex with men. A 29‐year‐old man visited our hospital for skin lesions on his lower lip, nipple–areola and penis. A positive syphilis serological test for rapid plasma reagin had a titer of 1:16; the patient also tested positive for specific antibodies against T. pallidum, with a cut‐off index of 39.0. Histopathological examination of a nipple–areola biopsy specimen revealed a thickened epidermis and dense infiltration of inflammatory cells extending from the upper dermal layers to the deep dermis. The inflammatory cells were composed of abundant lymphocytes, plasma cells, histiocytes and neutrophils. Immunohistochemical staining for T. pallidum using an anti‐T. pallidum antibody showed numerous spirochetes in the lower portion of the epidermis, scattered inside inflammatory cell infiltrate and perivascular sites throughout the dermis. Based on these findings, the patient was diagnosed with primary syphilis. Treatment with oral amoxicillin hydrate was started. Five days after starting treatment, a diffuse maculopapular rash (syphilitic roseola) occurred on his trunk and extremities. Perivascular cuffing due to T. pallidum was present throughout the dermis in the biopsy specimen of a localized lesion of primary syphilis. Moreover, syphilitic roseola, which indicates generalized dissemination of T. pallidum, developed during the course of treatment for primary syphilis. Therefore, we considered perivascular cuffing to be indicative of the dissemination phase.

Plasmocytosis circumorificialis successfully treated with topical fusidic acid ointment.

Plasmocytosis circumorificialis is a benign chronic inflammatory disease, which causes erythema, erosions, ulcers, nodules and related changes in and around the openings of the human body, and is histopathologically characterized by dense infiltration of the dermis by plasma cells. We recently encountered a 49‐year‐old man in whom this disease affected the lower lip. On initial examination in our department, a well‐demarcated region of erosion (10 mm × 5 mm), accompanied in part by formation of a crust, was noted on the left side of his lower lip. Histopathologically, the mucosal epithelium exhibited erosions, and dense plasma cell infiltration, without signs of atypia, was noted in the upper through middle layers of the lamina propria. On the basis of these findings, plasmocytosis circumorificialis was diagnosed. Because the patient had experienced repeated cycles of remission and relapse, despite topical treatment with various drugs (e.g. topical antibiotics and steroids), prior to referral to our department, we administered topical 2% fusidate sodium or Fucidin (Leo Pharmaceutical, Ballerup, Denmark) ointment. His eruption healed approximately 3 weeks after the start of this treatment. We report this case and discuss the findings reported in Japan on the development of plasmocytosis circumorificialis of the lips.

Contact dermatitis caused by bufexamac sparing the eruption of herpes zoster

Dear Editor, Contact dermatitis arising from the use of topical drugs usually causes eruption only in regions with drug application. However, contact dermatitis caused by bufexamac often induces skin lesions beyond such regions. Many reports have been published concerning contact dermatitis arising from the use of bufexamac. We report a case in which contact dermatitis arose from the use of bufexamac ointment for the treatment of herpes zoster. This case was characterized by the absence of erythema in herpes zoster-affected regions. The patient was a 73-year-old woman with an edematous erythema in the right breast to the right side of the abdomen and dorsal region. She had developed herpes zoster in the right thoracic 6 ⁄ 7 region 2 weeks previously and had received oral acyclovir therapy (4000 mg ⁄ day · 7 days) and topical treatment with bufexamac ointment at another facility. Herpes zoster had undergone crust formation, but the edematous erythema had developed in the regions of drug application 10 days after the start of topical bufexamac ointment therapy. Although the ointment was discontinued thereafter, the erythema expanded beyond the regions of drug application. On initial examination in our hospital, she presented with a well-demarcated edematous erythema, accompanied by itching, extending from the right breast to the right side of the thoracic ⁄ abdominal and dorsal regions. Erythema was not observed in the region affected by herpes zoster (Fig. 1a,b). Histopathologically, exocytosis and spongiosis were noted, accompanied by edema and vascular dilatation in the upper layer of the dermis and perivascular inflammatory cell infiltration (primarily by lymphocytes). Lymphocyte infiltration was more intense in the erythema-affected regions than in the erythema ()) region (herpes zoster-affected region), and larger counts of eosinophils were noted in the erythema-affected regions (Fig. 1c1,2). Immunohistochemically, CD1a (Dako, Carpentaria, CA, USA) staining revealed fewer dermal dendritic cells of the upper layer of the dermis in the erythema ()) region than in the erythema-affected regions (Fig. 1d1,2). Intercellular adhesion molecule-1 (ICAM-1; Santa Cruz Biotechnology, Santa Cruz, CA, USA) staining revealed lower counts of ICAM-1-expressing cells in the erythema ()) region than in the erythema-affected regions (Fig. 1e1,2). In patch testing, bufexamac ointment and 0.05–5% bufexamac in petrolatum yielded positive reactions with grade (+) according to the classification of the International Contact Dermatitis Research Group (Fig. 2). The patient was diagnosed with contact dermatitis arising from bufexamac. She was treated with oral betamethasone (1 mg ⁄ day), d-chlorpheniramine maleate (8 mg ⁄ day), ebastine (10 mg ⁄ day) and topical treatment with betamethasone butyrate propionate ointment. On day 7 of treatment, new erythema was noted in the right femoral region. Subsequently, the dose levels were gradually reduced, and contact dermatitis had healed by day 12. The present case was characterized by regions of contact dermatitis not including the herpes zoster-affected region, and several similar reports have been published. Katayama et al. reported a contact dermatitis caused by fradiomycin sulfate. In that report, close attention was paid to Langerhans cells, which are known to play important roles in the host defense system against herpes virus infection. It has been reported that in cases of viral infection (e.g. herpes simplex), counts of epidermal Langerhans cells are lower than usual or such cells are absent. Katayama et al. suggested that Langerhans cells are also decreased in herpes zoster via a similar mechanism, resulting in suppression of antigen-presenting function and leading to suppression of reaction in the herpes zoster-affected region. Harada et al. reported a drug eruption possibly due to carbamazepine. In that case, inflammation reaction was more intense in the region affected by disseminated erythema ⁄ papules than in the herpes zoster-affected region, though CD1a staining revealed no difference in chromatic response between these regions. The same investigators considered the possibility of an association of this finding with ICAM-1, on the basis of a previous report that ICAM-1 expression was lower in Langerhans cells infected with herpes zoster virus. ICAM-1 is a ligand for lymphocyte function-associated antigen-1 (LFA-1), which functions as an integrin on leukocytes. It is an adhesion molecule exhibiting increased expression in regions of inflammation and cancer cells and less expression in normal regions. Cell adhesion mediated by LFA-1 ⁄ ICAM-1 plays an important role in the activation of T lymphocytes by antigen-presenting cells within the tissue during the course of extravascular migration of leukocytes. Furthermore, for recognition of antigen signals by T lymphocytes and their activation, both the primary stimulus mediated by the T-cell receptor ⁄ CD3 complex and the co-stimulation mediated by cell surface molecules are required. On the basis of these findings, Harada et al. suggested that reduction of ICAM-1 expression inhibited the function noted above, possibly resulting in suppression of eruption in herpes zoster-affected regions. In the present case, although the count of epidermal Langerhans cells did not differ between the erythema ()) region and erythema-affected regions, the counts of dermal dendritic cells and dermal ICAM-1-expressing cells were lower in the erythema ()) regions. These changes probably suppressed antigen-presenting function and resulted in the lack of signs and symptoms

Erythroderma induced by morphine sulfate

Figure 2. Irregular acanthosis and scattered dyskeratotic cells were observed in the epidermis (hematoxylin–eosin, original magnification ·100). Dear Editor, Morphine sulfate is a pain reliever that is widely used to control persistent pain caused by cancer. The dermatological side-effects of morphine sulfate include pruritus and urticaria. Drug reactions caused by morphine sulfate, however, are almost unknown. Only one previously reported case of a drug reaction, an acute generalized exanthematous pustulosis reaction, caused by morphine sulfate has been reported. Here, we report a case of erythroderma that developed during treatment for multiple myeloma; the erythroderma turned out to be a drug reaction caused by morphine sulfate. A 73-year-old woman was diagnosed as having immunoglobulin (Ig)Aj type multiple myeloma. She had been hospitalized in the Internal Medicine Department of our hospital. Morphine sulfate was administrated to control severe pain caused by bone fractures associated with multiple myeloma. Two weeks after the initiation of this pain control procedure, eruptions were observed over her entire body. Prednisolone (20 mg ⁄day) was administrated p.o. to treat the skin lesions, and the dose was subsequently reduced to 10 mg ⁄day. The eruptions, however, did not subside, and the patient was referred to our department. The patient developed diffuse erythemas with fine scales over the arms and the trunk accompanied by severe itching (Fig. 1). Dark-red erythemas with some lichenification were present on her legs. The condition appeared to be an erythroderma accompanied by intense itching. The patient also developed a mild fever and enlarged lymph nodes. The presence of elevated eosinophil (14%, 896 ⁄lL) and serum IgA (970 mg ⁄dL) levels, as well as a low serum calcium level (8.4 mg ⁄dL) were also noted. A skin biopsy was excised from the back of the patient (Fig. 2). A histological study revealed irregular acanthosis with parakeratosis and scattered dyskeratotic cells in the epidermis. Lymphoid cell attachment at the

Novel and recurrent ATP2A2 mutations in Japanese patients with Darier’s disease

ABSTRACT Darier’s disease (DD, keratosis follicularis: OMIM#124200) is an autosomal dominant skin disorder characterized by multiple dark brown keratotic plaques and warty papules covered by thick crusts. Most cases of DD are caused by mutations in ATP2A2, which is expressed in both the skin and the brain. ATP2A2 encodes the cardiac muscle SERCA2a protein and the ubiquitously expressed SERCA2b. SERCA2 plays an important role as a calcium pump. It is thought that a mutation in ATP2A2 causes dyskeratosis and abnormality of cell-cell adhesion. Here, we report five DD patients from five independent families who presented or were referred to the Nagoya University Hospital in the past five years. We detected five mutations in ATP2A2, including a previously unreported mutation. We observed no apparent genotype/phenotype correlation between types and sites of the ATP2A2 mutations and DD phenotypes in the present series of DD patients. Genetic diagnosis from ATP2A2 mutation search is useful for the definite diagnosis of DD, although it is difficult to predict the severity and prognosis of skin symptoms from the results of the ATP2A2 mutation analysis in DD patients.