KEIO JOURNAL OF MEDICINE最新文献

We describe a case of sarcoidosis in a previously healthy 39-year-old man with the development of an acute kidney injury, requiring renal replacement therapy, as the first manifestation of the disease. The course of the disease was complicated by a сatheter-associated bloodstream infection. According to the histological examination of kidney biopsy samples, granulomatous interstitial nephritis was diagnosed. Extensive examination of the patient revealed persistent hypercalcemia, elevated transaminase levels, intrathoracic lymphadenopathy, and infiltrates in the lungs. Other diseases, such as anti-neutrophil cytoplasmic antibody-associated vasculitis, tuberculosis, autoimmune liver diseases, and systemic lupus erythematosus, were ruled out. The patient was treated with pulse therapy of methylprednisolone, which then switched to oral glucocorticoids (prednisolone 60 mg/day followed by a gradual decrease in the dose). The 9-month follow-up revealed a regression of lung lesions and improvement of the impaired renal function. The prednisolone dose was reduced to 7.5 mg/day, and renal replacement therapy was discontinued.

Coinfection of cytomegalovirus (CMV) and Mycobacterium tuberculosis presenting with acquired perforating dermatosis is a rare occurrence and remains poorly described in the literature. A man in his 40s, a farmer and chronic smoker, who was partially treated for tuberculosis, presented with a history of fever, weight loss, cough, generalized lymphadenopathy, severe pruritus, and skin lesions. Imaging findings suggested tuberculosis, which was confirmed by sputum examination. Histopathological examinations confirmed CMV lymphadenitis associated with acquired perforating dermatosis. Treatment included antitubercular therapy and a multidrug regimen for severe pruritus, leading to symptomatic improvement. Despite initial progress, the patient was lost to follow-up and later succumbed at home, emphasizing the importance of timely intervention for coinfected tuberculosis and cytomegalovirus diseases. This case highlights the rarity of cytomegalovirus and tuberculosis coinfection, the diagnostic complexities, the challenges associated with the treatment of intractable pruritus, and the necessity of ensuring proper follow-up.

Invasive urothelial carcinoma (UC) has diverse morphological presentations. Here, we describe the case of a Japanese woman aged in her early 60s with UC with unclear differentiation. The patient presented with distinct glandular differentiation and concurrent cystitis glandularis (CG) and intestinal metaplasia (IM) without a conventional UC component. Up to 2% of patients with bladder cancer develop adenocarcinoma. However, differentiating UC with glandular differentiation (UCg) from adenocarcinoma can be challenging. Although CG and IM are associated with adenocarcinoma, their presence does not necessarily imply that the comorbid cancer is adenocarcinoma. In this case, cytokeratin 7 (CK7) and CK5/6 positivity was assessed to establish the diagnosis of poorly differentiated UCg. A poorly differentiated pure UCg without conventional UC components has not yet been reported, which makes diagnosis extremely difficult. Moreover, because of the highly differentiated glandular structures within poorly differentiated UCs, the mechanism of tumorigenesis remains unclear. Further studies involving a larger case series should be conducted to elucidate the association between CG and IM and investigate the genetic background of these tumors, all of which would improve the accuracy of differentiation between poorly differentiated UC and adenocarcinoma.

The hair follicle is an appendage of the skin that undergoes hair cycles throughout life. Recently, numerous genes expressed in the hair follicles have been identified, and variants in some of these genes are now known to underlie hereditary hair diseases in humans. Hereditary hair diseases are classified into non-syndromic and syndromic forms. In the Japanese population, the non-syndromic form of autosomal recessive woolly hair, which is caused by founder pathogenic variants in the lipase H (LIPH) gene, is the most prevalent hereditary hair disease. In addition, other types of hereditary hair diseases are known in Japan, such as Marie-Unna hereditary hypotrichosis, hypohidrotic ectodermal dysplasia, and tricho-rhino-phalangeal syndrome. To ensure correct diagnoses and appropriate patient care, dermatologists must understand the characteristics of each hair disorder. Elucidation of the molecular basis of hereditary hair diseases can directly tell us which genes are crucial for morphogenesis and development of hair follicles in humans. Therefore, continuation of "wet laboratory" research for these diseases remains important. To date, several syndromic forms of hereditary hair diseases have been approved as designated intractable diseases in Japan. As part of our efforts in the Project for Research on Intractable Diseases through the Ministry of Health, Labour, and Welfare of Japan, we anticipate that more hereditary hair diseases be recognized as designated intractable diseases in the future, which will be to the benefit of the affected individuals.

Pachyonychia Congenita Project (PC Project) is an international patient advocacy organization dedicated to patients who suffer from pachyonychia congenita (PC). This condition is a painful and debilitating skin disorder caused by a mutation in one of five keratin genes: KRT6A, KRT6B, KRT6C, KRT16,or KRT17. Through two primary programs, namely the International Pachyonychia Congenita Consortium (IPCC) and the International Pachyonychia Congenita Research Registry (IPCRR), PC Project provides comprehensive patient support and diagnostics while uniting patients, researchers, physicians, and industry partners on a global level to advance research and drug development for meaningful treatments and, ultimately, a cure for PC.

Neurofibromatosis 1 (NF1), also known as von Recklinghausen disease, is one of the most common neurocutaneous genetic disorders. Loss of function of the NF1 gene results in overactivation of the RAS/MAPK pathway, leading to neurocutaneous manifestations and osseous abnormalities. Because of medical progress, molecular testing for NF1 after genetic counseling is now available in Japan. In addition, revised diagnostic criteria for NF1 were proposed by NF1 experts of an international panel in 2021. Because the overall degree of severity and manifestations in each patient are not predictable, age-specific annual monitoring and patient education by a multidisciplinary team are important for the management of NF1. Although treatment of plexiform neurofibroma has been challenging, selumetinib (an oral selective MEK1/2 inhibitor), which targets a pathway downstream of RAS, was approved in 2022 for use in children with inoperable, symptomatic plexiform neurofibromas in Japan. This article summarizes recent progress in diagnosis, clinical characteristics, and treatment of various manifestations of NF1 and proposes the future direction required to resolve unmet needs in patients with NF1 in Japan.

Gorlin syndrome and Cowden syndrome are hereditary diseases that are characterized by multiple malignancies, cutaneous symptoms, and various other abnormalities. Both disorders are caused by a mutation of the gene that regulates cell proliferation and growth, resulting in tumorigenesis. Representative mutations are mutation in the patched 1 gene (PTCH1) in Gorlin syndrome and mutation in the phosphatase and tensin homolog deleted from chromosome 10 (PTEN) gene in Cowden syndrome. Making a diagnosis of these diseases in the early years of life is important because detection of malignancies at an early stage is linked to improved prognosis. Both Gorlin syndrome and Cowden syndrome have cutaneous findings in the early phase in childhood, and the role of dermatologists is therefore important. These diseases are generally diagnosed by clinical criteria, but some patients who do not meet the criteria need genetic examinations including a genetic diagnostic panel and next-generation sequencing. The most important treatment and management are detection and resection of malignancies in the early stage, and targeted therapies have recently been used for treatment of tumors and other symptoms in these diseases. Although evidence of the effectiveness of targeted therapies has been limited, they are promising therapeutic options and further clinical trials are needed in the future.

Tuberous sclerosis complex (TSC) is an autosomal dominant inherited disease characterized by systemic hamartomas, neuropsychiatric symptoms known as TAND (TSC-associated neuropsychiatric disorders), and vitiligo. These symptoms are attributed to the constant activation of mechanistic target of rapamycin complex 1 (mTORC1) caused by genetic mutations in the causative genes TSC1 or TSC2. The elucidation of the pathogenesis of this disease and advances in diagnostic technologies have led to dramatic changes in the diagnosis and treatment of TSC. Diagnostic criteria have been created at a global level, and mTORC1 inhibitors have emerged as therapeutic agents for this disease. Previously, the treatment strategy was limited to symptomatic treatments such as surgery. Inhibitors of mTORC1 are effective against all symptoms of TSC, but they also have systemic side effects. Therefore, the need for a cross-disciplinary, collaborative medical care system has increased, resulting in the establishment of a practice structure known as the "TSC Board." Furthermore, to reduce the side effects of systemic administration of mTORC1 inhibitors, a topical formulation of mTORC1 inhibitor was developed in Japan for the treatment of skin lesions caused by TSC. This report summarizes the pathogenesis and current status of TSC and the contribution of the Neurocutaneous Syndrome Policy Research Group to the policies of the Ministry of Health, Labor, and Welfare with respect to this rare, intractable disease.

Pachyonychia congenita (PC) is a rare, autosomal dominant inherited disorder of keratinization that is characterized by a triad of focal palmoplantar keratoderma, plantar pain, and hypertrophic nail dystrophy. It can be debilitating, causing significantly impaired mobility. PC is diagnosed clinically alongside identification of a heterozygous pathogenic mutation in one of five keratin genes: KRT6A, KRT6B, KRT6C, KRT16, or KRT17. Each keratin gene mutation is associated with a distinct clinical phenotype, with variable age of onset and additional features, which has allowed classification by genotype. Additional features include pilosebaceous cysts, follicular hyperkeratosis, natal teeth, oral leukokeratosis, hidradenitis suppurativa, itching, and neurovascular structures. Although classed as rare, the prevalence of PC is likely to be underestimated. There is no cure or specific treatment for PC at present. Current treatments are limited to conservative measures to reduce plantar friction and trauma, mechanical debridement, topical treatments, and treatments for associated features or complications, most commonly infection. However, through active research in collaboration with PC Project, a patient-advocacy group, and the International PC Research Registry, a global registry of PC patients, there are now many new potential therapeutic options on the horizon. This review summarizes the clinical features associated with PC and highlights the current and future treatment of its manifestations.