Naoko Takeo

Pustular-type drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms due to carbamazepine with systemic muscle involvement

Drug‐induced hypersensitivity syndrome (DIHS)/drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe reaction usually associated with maculopapular eruptions and systemic involvement. Here we report the first case, to our knowledge, of DIHS/DRESS due to carbamazepine with acute generalized pustular bacterid‐like (AGPB‐like) eruptions and skeletal muscle involvement. Reviewing our case and the published work, we discuss pustular‐type DIHS/DRESS which, in most cases, involves acute generalized exanthematous pustulosis (AGEP)‐like skin eruptions in response to carbamazepine. Pustular eruptions may appear in relatively few cases of DIHS/DRESS, in particular, when the causative drug is carbamazepine and, even in cases of intractable pustular bacterid‐like eruptions, a reaction to a drug should be suspected. Skeletal muscle involvement may be associated with DIHS/DRESS as one of its systemic manifestations.

Epiplakin accelerates the lateral organization of keratin filaments during wound healing

BACKGROUND Epiplakin (EPPK) belongs to the plakin family of cytolinker proteins and, resembling other members of the plakin family such as BPAG1 (an autoantigen of bullous pemphigoid) and plectin, EPPK has plakin repeat domains (PRDs) that bind to intermediate filaments. Elimination of EPPK by gene targeting in mice resulted in the acceleration of keratinocyte migration during wound healing. EPPK is expressed in proliferating keratinocytes at wound edges and, in view of its putative function in binding to keratin, we postulated that the keratin network in EPPK-null (EPPK(-/-)) mice might be disrupted during wound healing. OBJECTIVE To examine this hypothesis and to determine the precise localization of EPPK in relation to keratin filaments, we compared the non-wounded and wounded epidermis of wild-type and EPPK(-/-) mice. METHODS Non-wounded epidermis and wounded epidermis from wild-type and EPPK(-/-) mice were examined by immunofluorescence staining and electron microscopy before and after double immunostaining. RESULTS EPPK was colocalized with keratin 17 (K17) more extensively than with other keratins examined in wounded epidermis. The expression of K5, K10, K6, and K17 was the same in EPPK(-/-) mice after wounding as in normal mice, but diameters of keratin filaments were reduced in EPPK(-/-) keratinocytes. Electron microscopy after immunostaining revealed that EPPK colocalized with K5, K10 and K6 after wounding in wild-type mice. CONCLUSION Our data indicate that EPPK accelerates keratin bundling in proliferating keratinocytes during wound healing and suggest that EPPK might contribute to reinforcement of keratin networks under mechanical stress.

Case of Mycobacterium haemophilum infection in a Japanese renal transplant patient and a review of Japanese cases

1 Wilmer WA, Magro CM. Calciphylaxis: emerging concepts in prevention, diagnosis, and treatment. Semin Dial 2002; 15: 172–186. 2 Edwards RB, Jaffe W, Arrowsmith J, Henderson HP. Calciphylaxis: a rare limb and life threatening cause of ischaemic skin necrosis and ulceration. Br J Plast Surg 2000; 53: 253–255. 3 Guldbakke KK, Khachemoune A. Calciphylaxis. Int J Dermatol 2007; 46: 231–238. 4 Lal G, Nowell AG, Liao J, Sugg SL, Weigel RJ, Howe JR. Determinants of survival in patients with calciphylaxis: a multivariate analysis. Surgery 2009; 146: 1028–1034.

Atypical pemphigus with exclusively anti-desmocollin 3-specific IgG antibodies

ejd.2012.1762 Auteur(s) : Yutaka Hatano1, Takashi Hashimoto2, Shunpei Fukuda2, Kazushi Ishikawa1, Mizuki Goto1, Yoshitaka Kai1, Naoko Takeo1, Osamu Okamoto1, Sakuhei Fujiwara1 fujiwara@oita-u.ac.jp 1 Department of Dermatology, Oita University, Idaigaoka1-1 Hasama, Yufu 879-5593, Japan 2 Department of Dermatology, Kurume University School of Medicine, Kurume University, Kurume 830-0011, Japan Antibodies against desmocollin 3 (Dsc3), together with other autoantibodies have been detected in some cases [...]

Association between HLA-DRB1*0405, -DQB1*0401 and -DQA1*0303 alleles and lamotrigine-induced cutaneous adverse drug reactions. A pilot case-control study from Japan

BACKGROUND Human leukocyte antigen (HLA) genotypes in lamotrigine -induced (LTG-induced) cutaneous adverse drug reactions (cADRs) have been described in several reports but controversy remains even for a given ethnic group. We attempted to clarify a possible association between LTG-induced cADRs and HLA alleles in Japanese patients. METHOD Sixteen subjects, including eight patients with LTG-induced cADRs and eight LTG-tolerant controls were included in this study. All eight patients with LTG-induced cADRs gave positive results in a drug-induced lymphocyte stimulation test (DLST) with LTG. We performed HLA-typing for HLA-A, -B, -C, -DRB1, -DQA1, -DQB1, -DPA1 and -DPB1, using PCR with sequence-specific oligonucleotide probes and multiple analyte profiling (xMAP) technology (Luminex System; Luminex Corporation, Austin, TX). We examined differences between allele frequencies in our two groups of subjects and the allele frequencies in the general Japanese population. RESULTS The frequencies of HLA-DRB1*0405, and HLA-DQB1*0401 alleles were higher in our LTG-cADRs patients than the reference frequencies in the general Japanese population. We also detected HLA-DQA1*0303 frequently in our LTG-cADRs patients, but data for this allele in the Japanese population was not available. Our observation was presumably due to the linkage disequilibrium among the three alleles. The haplotype frequency of HLA-DRB1*0405, DQB1*0401 and DQA1*0303 in our LTG-cADRs subjects was also different from the corresponding haplotype frequency in the database for the Japanese population and the difference was statistically significant. One patient with the HLA-DRB1*0405, -DQB1*0401 and DQA1*0303 haplotype was safely re-treated with LTG after results of a DLST with LTG ceased to be positive about 4 months after discontinuation of LTG. LIMITATIONS Our analysis included only 16 patients. Associations between LTG-induced cADRs and specific HLA loci will have to be confirmed in larger studies. CONCLUSIONS LTG-induced cADRs are associated with HLA-DRB1*0405, -DQB1*0401 and -DQA1*0303.

Drug-induced hypersensitivity syndrome due to carbapenem antibiotics.

Drug‐induced hypersensitivity syndrome (DIHS) is characterized by a serious adverse systemic reaction that usually appears after a 3–6‐week exposure to certain drugs, for example, anticonvulsants. Many different precipitating factors have been reported, but the pathophysiology of DIHS remains unknown. However, reactivation of members of the human herpesvirus (HHV) family, and of HHV‐6 in particular, has been reported in patients with DIHS. We report the case of a 64‐year‐old man who developed a generalized erythematous rash, fever, hepatic failure, lymphadenopathy and an increased number of atypical lymphocytes. In addition, reactivation of HHV‐6 and cytomegalovirus (CMV) was demonstrated by real‐time quantitative amplification by polymerase chain reaction. The patient was given a diagnosis of DIHS due to carbapenem antibiotics based on his clinical course, laboratory data, and results of lymphocyte‐stimulation tests with various drugs. This is the first report, to our knowledge, of DIHS induced by carbapenem antibiotics.

Hereditary lactate dehydrogenase M-subunit deficiency with late-developing pustular psoriasis-like lesions

Hereditary lactate dehydrogenase (LDH) M‐subunit deficiency is very rare and we have found reports of close to a dozen cases in the published work, two of which were associated with pustular psoriasis‐like lesions. We report a third case of pustular psoriasis‐like eruptions associated with LDH M‐subunit deficiency, which occurred 24 years after the diagnosis of LDH M‐subunit deficiency. These cases indicate that abnormal activity of LDH can induce pustular psoriatic lesions in the long term. Some patients with symptoms of hereditary LDH M‐subunit deficiency have antecedent annular scaly plaque lesions, that resemble psoriatic lesions. We discuss a hypothesis to explain this scenario.

A case of concurrent pemphigoid vegetans and pemphigus vegetans resolving without oral corticosteroid

of jet injector and the parameters used among various studies. The amount of pain can be reduced with the use of appropriate parameters. Pain severity correlates with the jet’s depth of penetration. We have observed that low driving pressure, low volume per spurt, smaller nozzle diameter and a longer distance (2–3 mm) between the tip of the nozzle and skin surface allow more superficial penetration of the jet into the skin. A low-pressure jet injector provides rapid, adequate and painless anaesthesia for a variety of dermatological procedures. The lack of needle use and the rapidity of the procedure reduce apprehension in the needle-phobic patient. For needle-phobic patients, the direct injection of BTX-A into the palms with the needle-free injector is also a justifiable option despite a 5–10% waste of BTX-A occurring through splash and splatter. Traditional jet injectors, such as Dermojet , have fixed driving pressures due to their spring-loaded mechanism. They are high-pressure devices with driving pressure varying between 1400 and 2000 psi. These devices do not work universally on different areas of the body and some manufacturers even warn against their use on the hands and fingers. Driving pressures used in our practice do not usually exceed 140 psi, which is at least 10 times lower than the driving pressure used in traditional jet injectors. Complications with higher-pressure traditional injectors include pain and considerable harm to vital nerves and vessels. The disadvantages of jet injection with the lowest possible pressure (140 psi) capable of inducing a subepidermal weal are minimal. The risk of infection is low with disposable anticontaminant devices and spacers combined with the use of advanced sterilization techniques. Soaking the hands in lukewarm water for 5–10 min helps induce a subepidermal weal with lower pressures. The driving pressure should be increased only when the weal fails to appear. At that time, it can be increased by increments of 10 psi until the anaesthetic weal becomes visible or a tiny blood spot appears into which BTX-A can be injected in a painless manner. The versatility of the pressure settings is because the new jet injectors are powered by carbon dioxide, which allows delivery of the injectate at the desired depth. Using a sterile jet injector on each patient avoids transmission of infection between patients. Because needle phobia is prevalent and has remained a therapeutic challenge, the importance of embracing needle-free injection systems in dermatology cannot be overemphasized.

Case of Mycoplasma pneumoniae infection with maculopapular‐type eruptions due to acetaminophen

have been reported but acneiform, purpuric and cutaneous eruption occurring along the lines of Blaschko have been also described. Only very few cases have developed more severe skin reactions including Stevens–Johnson’s syndrome or toxic epidermal necrolysis (Table 1). Mild to moderate eruptions usually appear in the first month of therapy and resolve quickly after drug withdrawal. Variable inflammatory histopathological patterns have been observed, including non-specific perivascular lymphocytic infiltrate, neutrophilic dermatosis-like reactions and diffuse interstitial granulomatous dermatitis with palisading degenerated collagen. To our knowledge, no cases of paronychia secondary to lenalidomide have been previously reported. The clinical features were rather similar to those observed in patients treated with epidermal growth factor receptor or mitogenactivated protein kinase inhibitors. In those cases, the underlying pathogenic mechanism remains unclear, although some angiogenic factors such as vascular endothelial growth factor have been proposed. According to the properties of lenalidomide, it can be hypothesized that a similar mechanism may be responsible for lenalidomide-induced paronychia. In conclusion, we would like to stress the development of paronychia as a previously unrecognized manifestation related to lenalidomide use. Dermatologists should have confidence in the management of this new drug and in its toxicity profile.

Case of juvenile pemphigus vulgaris which responded to i.v. immunoglobulin therapy.

apparent periodicity or recurrence. Thirty-seven patients, representing 52% of our series, had a chronic course characterized by fluctuating intermittent periods of exacerbations and short improvements, requiring almost continuous treatment. We also demonstrated that female sex, elevated erythrocyte sedimentation rate and C-reactive protein values, ACW involvement, peripheral synovitis, and the occurrence of two or more skin lesions at the onset are associated with a chronic course. In conclusion, we agree that diagnostic delays are important and that early recognition of SAPHO syndrome is of great importance. Therefore, as Zhao et al. affirmed, we firmly hope that nonrheumatological specialists, such as dermatologists, but also general practitioners and internists, will have greater confidence in recognizing this condition.