Hajime Nakano - Academia.edu (original) (raw)
Papers by Hajime Nakano
Case reports in dermatology
Linear immunoglobulin A (IgA) bullous dermatosis (LABD) is an autoimmune mucocutaneous disease ch... more Linear immunoglobulin A (IgA) bullous dermatosis (LABD) is an autoimmune mucocutaneous disease characterized by subepidermal blistering induced by IgA autoantibodies against several autoantigens in the basal membranous zone of the skin and mucosal tissue. Although diaminodiphenyl sulfone (DDS), also known as dapsone, is generally recognized as the first-line therapy for LABD, DDS can induce several severe side effects. We present a Japanese case of LABD with DDS-induced hemolytic anemia and alopecia. In the present case, the DDS-induced hemolytic anemia and hair loss made the DDS monotherapy difficult. When DDS is used in LABD patients with iron deficiency anemia (IDA), hemolytic anemia is concealed by IDA. It is thus necessary to carefully and frequently examine the laboratory data to find the signs of DDS-induced hemolytic anemia. Even though there is no literature on DDS-induced alopecia, alopecia was reported as one of the side effects of DDS in an FDA report, and, in our case, ...
Blue Rubber Bleb Nevus Syndrome Showing Vascular Skin Lesions Predominantly on the Face
Case reports in dermatology
An 81-year-old Japanese man presented with dark blue papules and nodules on his face. There were ... more An 81-year-old Japanese man presented with dark blue papules and nodules on his face. There were multiple soft papules and nodules, dark blue in color, compressive, and ranging in size from 2 to 10 mm. A few similar lesions were seen on the patient's right dorsal second toe and right buccal mucosa. There were no skin lesions on his trunk and upper limbs. The patient's past history did not include gastrointestinal bleeding or anemia. Histopathological examination showed dilated vascular spaces lined by the normal epithelium extending beneath the dermis and into the subcutaneous fat. Endoscopy of the gastrointestinal tract to check for colon involvement was not performed. X-ray images of the limbs revealed no abnormalities in the bones or joints. Laboratory investigations did not show anemia. Although we failed to confirm a diagnosis by endoscopy, the skin lesions, histopathological findings, lack of abnormal X-ray findings, and the presence of oral lesions as a part of gastro...
X-linked dominant protoporphyria: The first reported Japanese case
The Journal of Dermatology, 2015
A 12-year-old boy with photosensitivity since 3 years of age presented with small concavities on ... more A 12-year-old boy with photosensitivity since 3 years of age presented with small concavities on both cheeks, the nasal root and the dorsal surface of both hands. According to the clinical features, erythropoietic protoporphyria (EPP) was suspected. Urine and blood samples were tested for porphyrin derivatives, which revealed a markedly elevated level of erythrocyte protoporphyrin (EP) and a diagnosis of EPP was made. The patient's mother had no photosensitivity, however, lesions appearing slightly as small scars were found on the dorsum of her right hand; his elder sister and father showed no rash. The EP levels were elevated in samples from his mother and mildly elevated in those from his elder sister and father. To obtain a definitive diagnosis, genetic analyses were performed using samples from all family members, which revealed no mutations in the ferrochelatase-encoding gene (FECH), which is responsible for EPP. Instead, a pathological mutation of the 5-aminolevulinic acid synthase-encoding gene (ALAS2) was identified in samples from the patient, his mother and his elder sister, confirming a definitive diagnosis of X-linked dominant protoporphyria (XLDPP). This is the first Japanese family reported to have XLDPP, demonstrating evidence of the condition in Japan. In addition, because XLDPP is very similar to EPP in its clinical aspects and laboratory findings, a genetic analysis is required for the differential diagnosis.
Case Reports in Dermatology, 2015
Erythema induratum of Bazin in a patient with scrofuloderma
European journal of dermatology : EJD, Jan 3, 2015
A novel deletion mutation of the ATP2C1 gene in a family with Hailey-Hailey disease
European journal of dermatology : EJD, Jan 3, 2015
Mycosis fungoides bullosa associated with bullous pemphigoid
International Journal of Dermatology, 2015
Effect of cytokines and ultraviolet B radiation on the promoter activity of the metallothionein gene in keratinocytes
Advances in Bioscience and Biotechnology, 2013
CARD14 Glu138 mutation in familial pityriasis rubra pilaris does not warrant differentiation from familial psoriasis
The Journal of Dermatology, 2015
Some familial cases of pityriasis rubra pilaris (PRP) have the CARD14 gene mutations that are als... more Some familial cases of pityriasis rubra pilaris (PRP) have the CARD14 gene mutations that are also detected in familial psoriasis vulgaris. However, genotype-phenotype correlation in these two entities is poorly understood. Here, we report a case of PRP with a new mutation in CARD14. Genomic analysis of a 40-year-old female patient with sporadic PRP type V identified a heterozygous dominant c.412G>A mutation (p.Glu138Lys) in CARD14. Two types of CARD14 mutations causing Glu138 substitutions have been reported in cases of familial PRP and pustular psoriasis. All three types, including the present case, are predicted to cause similar loss of the negative charges at this site. This suggests that the difference in molecular charge and the resulting change in molecular interaction around the N-terminal end of the coiled-coil region of CARD14 molecule do not determine the phenotypic differences between psoriasis and PRP.
Case Reports in Clinical Medicine, 2014
Intralymphatic histiocytosis is characterized by dilated vessels containing aggregates of mononuc... more Intralymphatic histiocytosis is characterized by dilated vessels containing aggregates of mononuclear histiocytes in their lumina, and the majority of cases have been associated with rheumatoid arthritis (RA). We report a case of a 61-year-old woman with RA who presented with livedolike erythema and red papules around the right elbow and forearm. Histological examinations demonstrated numerous dilated vessels in the dermis partially filled with medium-to large-sized mononuclear cells. Immunohistochemically, most of the intraluminal cells were CD68-positive histiocytes. Endothelial cells were positive for D2-40, a marker for lymphatic endothelial cells. We diagnosed the patient with intralymphatic histiocytosis based on these clinical and histological findings. Interestingly, the skin manifestations exacerbated during the course of the disease when the swelling of the patient's right elbow joint progressed. Then, the puncture of content fluid of the joint was performed, since then, the symptoms of the skin lesion immediately improved. These observations suggest a possible association between the eruptions of intralymphatic histiocytosis and the involved joint. The results suggest that such skin eruptions may be ameliorated by treating severe arthritis.
Case Reports in Clinical Medicine, 2014
A 60-year-old Japanese woman was referred to our hospital for yellow-brown plaques accompanied by... more A 60-year-old Japanese woman was referred to our hospital for yellow-brown plaques accompanied by ulceration on her left lower leg. Her medical history included neither diabetes mellitus nor minor trauma. A histopathological examination of the plaques showed necrobiotic changes within the dermal collagen surrounded by granulomas that comprised lymphocytes, histiocytes, and giant cells. The lower dermis revealed fibrotic changes that extended into the subcutaneous tissue. The patient's blood glucose and glycated hemoglobin levels were within the normal ranges. We considered a diagnosis of necrobiosis lipoidica (NL) in the absence of diabetes mellitus. We reviewed 116 cases of NL that were reported in the Japanese medical literature between 1986 and 2014 and found that NL onset was most common in individuals of both sexes ≥ 60 years of age. Previous reports that reviewed NL cases in the Japanese medical literature that were published during the1900s indicated that NL occurs in people ≥ 40 years of age. We suggest that the aging population and increasingly longer life spans have increased the average age of NL onset in Japan. With regard to treatments, there were no effective treatments, but skin grafts were curative. NL treatment is very difficult, especially when ulcers are present; hence, we suggest that further research is needed to determine effective NL treatments.
Two cases of recessive dystrophic epidermolysis bullosa diagnosed as severe generalized
The Journal of Dermatology, 2011
Recessive dystrophic epidermolysis bullosa (RDEB) is a congenital bullous disease resulting from ... more Recessive dystrophic epidermolysis bullosa (RDEB) is a congenital bullous disease resulting from defective anchoring fibrils at the dermal-epidermal junction and mutations in the type VII collagen gene. In this report, we describe two patients with severe generalized RDEB. Patient 1 was a 24-day-old male infant, and patient 2 was a 1-day-old female infant. Immunofluorescence microscopy demonstrated absence of type VII collagen labeling in a skin sample of patient 1, and reduced staining in patient 2. Electron microscopy revealed absence of anchoring fibrils below the lamina densa in patient 1, and reduced or rudimentary anchoring fibrils in patient 2. Mutation analyses of COL7A1 in these patients revealed heteroallelic recessive mutations which resulted in premature termination codons (PTC): 6573+1G>C in intron81 and 886del6ins14 in exon 7 in patient 1, and 6573+1G>C in intron81 and 4535insC in exon 44 in patient 2. Heteroallelic combinations of PTC mutation generally result in the severe generalized type. Patient 2 has developed a digital fusion at age 2, which is a typical manifestation of severe generalized RDEB. The RDEB subtype is considered to be determined based on comprehensive information, including analysis of alleles, protein expression, ultrastructure and clinical symptoms after growth. However, mutation analyses of COL7A1 can provide valuable information estimating a diagnosis in early infancy.
Acta dermato-venereologica, 2011
Molecular medicine reports
Keratinocytes play an important role in the inflammatory response of the skin. UVB stimulates ker... more Keratinocytes play an important role in the inflammatory response of the skin. UVB stimulates keratinocytes to secrete several cytokines. To our knowledge, there are no reports that have examined which layer or cell type is responsible for producing these cytokines. Thus, in this study we performed immunohistochemical experiments to determine the potential cells or layers that express interleukin (IL)-1 and IL-6. The results show that the expression of IL-1α and IL-6 was induced 3 and 6 h after irradiation, respectively. Furthermore, IL-1α was maximally expressed earlier than IL-6, suggesting that IL-1α exists in the cytokine cascade of the UVB response upstream of IL-6. In addition, IL-1α expression began in the upper layers of the epidermis, whereas all layers expressed IL-6. This study provides further insight into the roles of cytokines in UVB-induced skin inflammation.
The Journal of dermatology, 2008
The most life-threatening complication developing in patients with recessive dystrophic epidermol... more The most life-threatening complication developing in patients with recessive dystrophic epidermolysis bullosa (RDEB) is squamous cell carcinoma (SCC). To improve patient prognosis, early detection of regional lymph node metastasis is required. Herein, we report a patient diagnosed with non-Hallopeau-Siemens RDEB who developed SCC on the left foot with inguinal lymph node swelling. Use of the sentinel node biopsy (SNB) technique favorably minimized defective damage to the inguinal region in this case. Genetic analysis identified one novel COL7A1 mutation, a maternal c.238G > C (p.A80P) and one previously reported mutation, a paternal c.3631C > T (p.Q1211X). A published work review demonstrated that no COL7A1 mutations specific for SCC development in RDEB have previously been identified. It remains unclear if SNB in combination with gene diagnosis is beneficial for the management of SCC in RDEB patients, however, because of the limited number of case reports. To address this iss...
Anti-laminin γ1 pemphigoid associated with ulcerative colitis and psoriasis vulgaris showing autoantibodies to laminin γ1, type XVII collagen and laminin-332
European journal of dermatology : EJD, Jan 17, 2015
Two Japanese familial cases of punctate palmoplantar keratoderma caused by a novel AAGAB mutation, c.191_194delCAAA
Journal of dermatological science, Jan 16, 2015
ABSTRACT Corresponding author. Tel.: +81 172 39 5087; fax: +81 172 37 6060.
A reddish, pedunculated, granulomatous nodule on the nasal dorsum
Clinical and experimental dermatology, Jan 22, 2015
Case reports in dermatology
Linear immunoglobulin A (IgA) bullous dermatosis (LABD) is an autoimmune mucocutaneous disease ch... more Linear immunoglobulin A (IgA) bullous dermatosis (LABD) is an autoimmune mucocutaneous disease characterized by subepidermal blistering induced by IgA autoantibodies against several autoantigens in the basal membranous zone of the skin and mucosal tissue. Although diaminodiphenyl sulfone (DDS), also known as dapsone, is generally recognized as the first-line therapy for LABD, DDS can induce several severe side effects. We present a Japanese case of LABD with DDS-induced hemolytic anemia and alopecia. In the present case, the DDS-induced hemolytic anemia and hair loss made the DDS monotherapy difficult. When DDS is used in LABD patients with iron deficiency anemia (IDA), hemolytic anemia is concealed by IDA. It is thus necessary to carefully and frequently examine the laboratory data to find the signs of DDS-induced hemolytic anemia. Even though there is no literature on DDS-induced alopecia, alopecia was reported as one of the side effects of DDS in an FDA report, and, in our case, ...
Blue Rubber Bleb Nevus Syndrome Showing Vascular Skin Lesions Predominantly on the Face
Case reports in dermatology
An 81-year-old Japanese man presented with dark blue papules and nodules on his face. There were ... more An 81-year-old Japanese man presented with dark blue papules and nodules on his face. There were multiple soft papules and nodules, dark blue in color, compressive, and ranging in size from 2 to 10 mm. A few similar lesions were seen on the patient's right dorsal second toe and right buccal mucosa. There were no skin lesions on his trunk and upper limbs. The patient's past history did not include gastrointestinal bleeding or anemia. Histopathological examination showed dilated vascular spaces lined by the normal epithelium extending beneath the dermis and into the subcutaneous fat. Endoscopy of the gastrointestinal tract to check for colon involvement was not performed. X-ray images of the limbs revealed no abnormalities in the bones or joints. Laboratory investigations did not show anemia. Although we failed to confirm a diagnosis by endoscopy, the skin lesions, histopathological findings, lack of abnormal X-ray findings, and the presence of oral lesions as a part of gastro...
X-linked dominant protoporphyria: The first reported Japanese case
The Journal of Dermatology, 2015
A 12-year-old boy with photosensitivity since 3 years of age presented with small concavities on ... more A 12-year-old boy with photosensitivity since 3 years of age presented with small concavities on both cheeks, the nasal root and the dorsal surface of both hands. According to the clinical features, erythropoietic protoporphyria (EPP) was suspected. Urine and blood samples were tested for porphyrin derivatives, which revealed a markedly elevated level of erythrocyte protoporphyrin (EP) and a diagnosis of EPP was made. The patient's mother had no photosensitivity, however, lesions appearing slightly as small scars were found on the dorsum of her right hand; his elder sister and father showed no rash. The EP levels were elevated in samples from his mother and mildly elevated in those from his elder sister and father. To obtain a definitive diagnosis, genetic analyses were performed using samples from all family members, which revealed no mutations in the ferrochelatase-encoding gene (FECH), which is responsible for EPP. Instead, a pathological mutation of the 5-aminolevulinic acid synthase-encoding gene (ALAS2) was identified in samples from the patient, his mother and his elder sister, confirming a definitive diagnosis of X-linked dominant protoporphyria (XLDPP). This is the first Japanese family reported to have XLDPP, demonstrating evidence of the condition in Japan. In addition, because XLDPP is very similar to EPP in its clinical aspects and laboratory findings, a genetic analysis is required for the differential diagnosis.
Case Reports in Dermatology, 2015
Erythema induratum of Bazin in a patient with scrofuloderma
European journal of dermatology : EJD, Jan 3, 2015
A novel deletion mutation of the ATP2C1 gene in a family with Hailey-Hailey disease
European journal of dermatology : EJD, Jan 3, 2015
Mycosis fungoides bullosa associated with bullous pemphigoid
International Journal of Dermatology, 2015
Effect of cytokines and ultraviolet B radiation on the promoter activity of the metallothionein gene in keratinocytes
Advances in Bioscience and Biotechnology, 2013
CARD14 Glu138 mutation in familial pityriasis rubra pilaris does not warrant differentiation from familial psoriasis
The Journal of Dermatology, 2015
Some familial cases of pityriasis rubra pilaris (PRP) have the CARD14 gene mutations that are als... more Some familial cases of pityriasis rubra pilaris (PRP) have the CARD14 gene mutations that are also detected in familial psoriasis vulgaris. However, genotype-phenotype correlation in these two entities is poorly understood. Here, we report a case of PRP with a new mutation in CARD14. Genomic analysis of a 40-year-old female patient with sporadic PRP type V identified a heterozygous dominant c.412G>A mutation (p.Glu138Lys) in CARD14. Two types of CARD14 mutations causing Glu138 substitutions have been reported in cases of familial PRP and pustular psoriasis. All three types, including the present case, are predicted to cause similar loss of the negative charges at this site. This suggests that the difference in molecular charge and the resulting change in molecular interaction around the N-terminal end of the coiled-coil region of CARD14 molecule do not determine the phenotypic differences between psoriasis and PRP.
Case Reports in Clinical Medicine, 2014
Intralymphatic histiocytosis is characterized by dilated vessels containing aggregates of mononuc... more Intralymphatic histiocytosis is characterized by dilated vessels containing aggregates of mononuclear histiocytes in their lumina, and the majority of cases have been associated with rheumatoid arthritis (RA). We report a case of a 61-year-old woman with RA who presented with livedolike erythema and red papules around the right elbow and forearm. Histological examinations demonstrated numerous dilated vessels in the dermis partially filled with medium-to large-sized mononuclear cells. Immunohistochemically, most of the intraluminal cells were CD68-positive histiocytes. Endothelial cells were positive for D2-40, a marker for lymphatic endothelial cells. We diagnosed the patient with intralymphatic histiocytosis based on these clinical and histological findings. Interestingly, the skin manifestations exacerbated during the course of the disease when the swelling of the patient's right elbow joint progressed. Then, the puncture of content fluid of the joint was performed, since then, the symptoms of the skin lesion immediately improved. These observations suggest a possible association between the eruptions of intralymphatic histiocytosis and the involved joint. The results suggest that such skin eruptions may be ameliorated by treating severe arthritis.
Case Reports in Clinical Medicine, 2014
A 60-year-old Japanese woman was referred to our hospital for yellow-brown plaques accompanied by... more A 60-year-old Japanese woman was referred to our hospital for yellow-brown plaques accompanied by ulceration on her left lower leg. Her medical history included neither diabetes mellitus nor minor trauma. A histopathological examination of the plaques showed necrobiotic changes within the dermal collagen surrounded by granulomas that comprised lymphocytes, histiocytes, and giant cells. The lower dermis revealed fibrotic changes that extended into the subcutaneous tissue. The patient's blood glucose and glycated hemoglobin levels were within the normal ranges. We considered a diagnosis of necrobiosis lipoidica (NL) in the absence of diabetes mellitus. We reviewed 116 cases of NL that were reported in the Japanese medical literature between 1986 and 2014 and found that NL onset was most common in individuals of both sexes ≥ 60 years of age. Previous reports that reviewed NL cases in the Japanese medical literature that were published during the1900s indicated that NL occurs in people ≥ 40 years of age. We suggest that the aging population and increasingly longer life spans have increased the average age of NL onset in Japan. With regard to treatments, there were no effective treatments, but skin grafts were curative. NL treatment is very difficult, especially when ulcers are present; hence, we suggest that further research is needed to determine effective NL treatments.
Two cases of recessive dystrophic epidermolysis bullosa diagnosed as severe generalized
The Journal of Dermatology, 2011
Recessive dystrophic epidermolysis bullosa (RDEB) is a congenital bullous disease resulting from ... more Recessive dystrophic epidermolysis bullosa (RDEB) is a congenital bullous disease resulting from defective anchoring fibrils at the dermal-epidermal junction and mutations in the type VII collagen gene. In this report, we describe two patients with severe generalized RDEB. Patient 1 was a 24-day-old male infant, and patient 2 was a 1-day-old female infant. Immunofluorescence microscopy demonstrated absence of type VII collagen labeling in a skin sample of patient 1, and reduced staining in patient 2. Electron microscopy revealed absence of anchoring fibrils below the lamina densa in patient 1, and reduced or rudimentary anchoring fibrils in patient 2. Mutation analyses of COL7A1 in these patients revealed heteroallelic recessive mutations which resulted in premature termination codons (PTC): 6573+1G>C in intron81 and 886del6ins14 in exon 7 in patient 1, and 6573+1G>C in intron81 and 4535insC in exon 44 in patient 2. Heteroallelic combinations of PTC mutation generally result in the severe generalized type. Patient 2 has developed a digital fusion at age 2, which is a typical manifestation of severe generalized RDEB. The RDEB subtype is considered to be determined based on comprehensive information, including analysis of alleles, protein expression, ultrastructure and clinical symptoms after growth. However, mutation analyses of COL7A1 can provide valuable information estimating a diagnosis in early infancy.
Acta dermato-venereologica, 2011
Molecular medicine reports
Keratinocytes play an important role in the inflammatory response of the skin. UVB stimulates ker... more Keratinocytes play an important role in the inflammatory response of the skin. UVB stimulates keratinocytes to secrete several cytokines. To our knowledge, there are no reports that have examined which layer or cell type is responsible for producing these cytokines. Thus, in this study we performed immunohistochemical experiments to determine the potential cells or layers that express interleukin (IL)-1 and IL-6. The results show that the expression of IL-1α and IL-6 was induced 3 and 6 h after irradiation, respectively. Furthermore, IL-1α was maximally expressed earlier than IL-6, suggesting that IL-1α exists in the cytokine cascade of the UVB response upstream of IL-6. In addition, IL-1α expression began in the upper layers of the epidermis, whereas all layers expressed IL-6. This study provides further insight into the roles of cytokines in UVB-induced skin inflammation.
The Journal of dermatology, 2008
The most life-threatening complication developing in patients with recessive dystrophic epidermol... more The most life-threatening complication developing in patients with recessive dystrophic epidermolysis bullosa (RDEB) is squamous cell carcinoma (SCC). To improve patient prognosis, early detection of regional lymph node metastasis is required. Herein, we report a patient diagnosed with non-Hallopeau-Siemens RDEB who developed SCC on the left foot with inguinal lymph node swelling. Use of the sentinel node biopsy (SNB) technique favorably minimized defective damage to the inguinal region in this case. Genetic analysis identified one novel COL7A1 mutation, a maternal c.238G > C (p.A80P) and one previously reported mutation, a paternal c.3631C > T (p.Q1211X). A published work review demonstrated that no COL7A1 mutations specific for SCC development in RDEB have previously been identified. It remains unclear if SNB in combination with gene diagnosis is beneficial for the management of SCC in RDEB patients, however, because of the limited number of case reports. To address this iss...
Anti-laminin γ1 pemphigoid associated with ulcerative colitis and psoriasis vulgaris showing autoantibodies to laminin γ1, type XVII collagen and laminin-332
European journal of dermatology : EJD, Jan 17, 2015
Two Japanese familial cases of punctate palmoplantar keratoderma caused by a novel AAGAB mutation, c.191_194delCAAA
Journal of dermatological science, Jan 16, 2015
ABSTRACT Corresponding author. Tel.: +81 172 39 5087; fax: +81 172 37 6060.
A reddish, pedunculated, granulomatous nodule on the nasal dorsum
Clinical and experimental dermatology, Jan 22, 2015