A 70-year-old woman presented with multiple erythemas on her entire body that she had noticed four days previously. She had been prescribed pregabalin and three other drugs for leg paralysis following a surgery for a spinal cord tumor three years previously. On examination, multiple typical target lesions distributed over the trunk and extremities were observed. Microscopic examination revealed vacuolar change in the dermo-epidermal junction and several individual necrotic keratinocytes. A drug-induced lymphocyte stimulation test was performed for each of the four drugs, and the stimulation index value was only positive for pregabalin. The erythema subsided immediately after pregabalin intake was stopped, and oral prednisolone therapy was initiated. Therefore, we diagnosed the patient with erythema multiforme-type drug eruption due to pregabalin. Drug eruption caused by pregabalin is very rare, and to our knowledge, only five cases (not including our case) have been reported thus far. We discuss six cases of pregabalin-induced drug-eruptions, including five previously reported cases and the present case. Of these six cases, severe drug eruption was reported in three cases. Two of these three cases of severe drug eruption involved erythemamultiforme-type drug eruption (one of these cases was the present case), and one case involved drug-induced hypersensitivity syndrome. Furthermore, it should be noted that the two cases of erythema multiforme-type eruption developed between 11 months and 3 years of the first intake of pregabalin. Prescription of pregabalin for postherpetic neuralgia has been increased. Thus, clinicians should pay attention to drug eruption throughout the window of management with pregabalin and not just at the initiation of drug therapy.

A 66 year-old man has had depigmented lesions on his scalp, face, and extremities since 8 years before visiting Yamaguchi University Hospital. While he was treated as vitiligo vulgaris, he has gradually had painful folliculitis-like eruptions on the scalp. As the eruptions on the scalp were intractable, he was introduced to our hospital. On his first visit, he had multiple folliculitis-like eruptions with erythema, as well as scarring and hyperkeratotic lesions on the face and dorsal hands. Based on the findings obtained from skin biopsy and laboratory investigations, he was diagnosed as cutaneous (discoid) lupus erythematosus, and the administration of oral hydroxychloroquine has been started. As the result, the eruptions on the scalp have quickly been resolved, and scarring erythema has also been improved. While the typical scalp lesion of cutaneous lupus erythematosus is scarring alopecia, it is relatively rare that folliculitis-like eruptions appear as a symptom of the disease. We postulate that the patient showed such unusual eruptions due to because he has had male-pattern alopecia. Our report further underscores the efficacy of hydroxychloroquine for the treatment of cutaneous lupus erythematosus.

We report the case of a 48-year-old Japanese man who was taking phenytoin for epilepsy and developed anti-laminin γ1 pemphigoid. Although steroid pulse therapy and high-dose intravenous immunoglobulin (IVIG) therapy as well as immunosuppressive drugs were administered, the erythema relapsed and blister formed again when prednisolone was tapered. We noticed that phenytoin weakened the effects of prednisolone ; therefore, we discontinued phenytoin administration. Thereafter, disease activity decreased. In dermatology practice, clinicians have many opportunities to prescribe steroids. It is likely that medicine may be prescribed without the consideration of combination contraindications. Through this case, we reaffirmed the importance of checking drug interactions.

A 58-year-old man had developed erythema and tense bullae on his trunk and extremities along with symptoms on his ocular and oral mucosa 2 weeks before his first visit to Yamaguchi University Hospital. Direct immunofluorescence using a biopsy specimen from the erythema on the trunk showed linear deposition of IgG, IgA, and C3 along the dermal-epidermal junction (DEJ). Indirect immunofluorescence of the patient's serum showed linear deposition of IgG along the dermal side of the DEJ on 1M NaCl-split skin of a normal control individual. Furthermore, western blot analysis demonstrated that IgG in the patient's serum reacted with a 290 kDa-protein in the dermal extracts from a control individual that corresponded to the molecular weight of collagen Ⅶ (COL7). Based on these findings, we diagnosed the patient with epidermolysis bullosa acquisita (EBA). We initially treated him with oral prednisolone and azathioprine. However, the disease activity was not completely suppressed. We additionally administered intravenous immunoglobulin and cyclophosphamide pulse therapies ; thereafter, the symptoms gradually reduced. EBA with ocular involvement is rare, and in this case, we suggest that IgA-type autoantibodies likely played a role in the pathogenesis in addition to IgG-type autoantibodies against COL7.

A 62-year-old woman visited our outpatient clinic with an approximately 5-year history of recurrent erythematous plaques accompanied by itching on the head and pubic area. She had been diagnosed with seborrheic dermatitis by a local doctor and treated with the strongest topical steroids (clobetasol propionate) and an oral anti-allergic drug. Several months before the referral, she developed erosions in the auricular area and around the nostrils because of scratching, and the rash extended to her entire body, leading to localized hair loss from her scalp. Symptom management was difficult ; therefore, she was referred to us for further evaluation and treatment. Based on the results of the bacterial culture and skin biopsy of the rash, she was diagnosed with generalized psoriasis and concomitant Staphylococcus impetigo. First, in order to control the impetigo, we reduced the dose of the topical steroid, and administered oral and topical antibacterial drugs based on the drug sensitivity test results. Then, we administered subcutaneous injections with monoclonal antibodies that inhibited IL-17A (secukinumab was used first, followed by ixekizumab) to treat the extended and exacerbated psoriasis. After the treatment, her rash and alopecia reduced. Based on this case, we concluded that refractory and recurrent psoriasis concomitant bacterial skin infection can be managed with the following : (1) adequate control of the bacterial infection with antibacterial drugs and (2) concurrent use of biological products targeting IL-17A that are considered relatively safe for patients with bacterial infections.

A 92-year-old man had a 2-month history of head nodule with bleeding. A partial biopsy of the lesion was performed, and histologically it showed proliferation of fibroblast-like spindle cells with marked cellular pleomorphism and atypia. Immunohistochemically, the tumor cells were focally and weakly positive for α-SMA, h-caldesmon, and calponin, but were negatively stained for desmin. Thus, leiomyosarcoma (LMS) was suspected. The nodule was widely excised and histological examination revealed that it was a dermal well-circumscribed nodule composed of haphazardly arranged spindle cells and pleomorphic epithelioid cells admixed with multi-nuclear giant cells and showing atypical mitotic activity. Immunohistochemically, the tumor cells were focally positive for α-SMA and h-caldesmon, but were negatively stained for desmin, calponin, CK5/6, p40, p63, AE1/AE3, S-100p, CD31, and CD34. Thus, we diagnosed the nodule as atypical fibroxanthoma (AFX). AFX should be distinguished from several spindle cell tumors or epithelioid cell tumors such as undifferentiated pleomorphic sarcoma. In our case, LMS was listed as one of the differential diagnoses, but the tumor was finally diagnosed as AFX due to its clear demarcation in the dermis, with only focally positive immunostaining for α-SMA and h-caldesmon. Partial biopsy was inadequate for the differential diagnosis between AFX and LMS, and evaluation of the entire tumor was necessary to achieve a definitive diagnosis.

A 75-year-old woman presented with purple-red nodules on the left lower thigh about half a year before her first visit. More similar tumors gradually appeared and spread to her left lower thigh. In the skin biopsy, spindle-shaped tumor cells proliferated and formed lumens throughout the dermis, and the lumens were full of red blood cells. Some red blood cells leaked outside the blood vessel. On immunostaining, the tumor cells were positive for CD31 in the cell membrane and LANA-1 in the nucleus ; they were diagnosed as Kaposi's sarcoma. One and a half years before her first visit, she developed optic neuromyelitis and after steroid pulse treatment, she started taking oral prednisolone (PSL) 50 mg and tacrolimus. At the first visit to our department, she was taking 10 mg of PSL and 4 mg of tacrolimus. She was believed to be immunosuppressed because she was taking oral PSL and tacrolimus for a long time. In addition, both HIV antigen and antibody were negative, and the possibility of iatrogenic Kaposi's sarcoma was high. Chest computed tomography (CT) revealed a pulmonary nodular shadow ; further, upper and lower gastrointestinal endoscopy and bronchoscopy showed disseminated lesions in the stomach and the bronchus. All these lesions were considered lesions of Kaposi's sarcoma. After the diagnosis, tacrolimus was discontinued, and PSL was gradually reduced from 10 mg/day to 7 mg/day in 3 months ; subcutaneous nodules of her lower leg were reduced in size in 3 months. However, after the patient developed pneumonia and urinary tract infection, her general condition deteriorated. The subcutaneous tumors increased and spread to both the legs, and pulmonary nodular shadows increased on the chest CT simultaneously. About 2 months after the development of pneumonia and urinary tract infection, she died because of respiratory failure. The condition of patients with iatrogenic Kaposi's sarcoma is usually improved by reduction or withdrawal of the immunosuppressive drugs. Although this patient's condition temporarily improved by withdrawal and reduction of tacrolimus and PSL, respectively, along with the worsening of the general condition, Kaposi's sarcoma lesions exacerbated simultaneously.

A 77-year-old woman presented with a nodule on her right thigh. She was unsure about when she noticed the nodule. A physical examination revealed a 1-cm sized dark red to blue subcutaneous nodule. We considered the diagnosis of epidermoid cyst and performed an excisional biopsy. Histopathological examination revealed small tumor nests in the pools of mucinous material separated by fibrous septa located in the dermis to the subcutaneous adipose tissue. The mucinous material was positive for alcian blue at pH2.5 and PAS. Immunohistochemically, the tumor cells were positive for CK7 and GCDFP15 and partially positive for CK20. Complete clinical and radiological examination revealed no neoplasm of other organs. Finally, the tumor was diagnosed as a mucinous carcinoma of the skin (MCS). MCSs frequently involve the head and the neck ; they rarely develop in the lower extremities. Therefore, MCS needs to be considered as a deferential diagnosis in such patients.

Immunoglobulin G4-related disease (IgG4-RD) is a recently established clinical entity characterized by elevated serum IgG4 level and tissue infiltration of IgG4 + plasma cells. IgG4-RD can affect multiple organs, such as the pancreas, kidneys, lacrimal glands, and salivary glands. Skin lesions associated with IgG4-related disease are diverse, and some present with clinical symptoms and pathological findings resembling those of pseudolymphoma. In the present case, a reddish mass with a rapidly increasing tendency was found in the nose, and pathological findings showed dense plasma cell infiltration and lymphoid follicle formation in the dermis. No gene rearrangement band of immunoglobulin was detected, and the IgG4/IgG ratio was 30%. The serum IgG4 level was elevated ; however, there were no visceral lesions. The patient was finally diagnosed with IgG4-related pseudolymphoma. It is speculated that IgG4-related skin disease is included in pseudolymphoma, defined as benign lymphoproliferative disease of unknown cause.

Case 1. A Japanese woman presented to the hospital for the infarction in the left middle cerebral artery region. At the time of transportation, she had already suffered from herpes zoster in the second and third branch of the left trigeminal nerve regions. Case 2. A Japanese woman was treated with Famciclovir and Vidarabine ointment for herpes zoster in the third branch of the right trigeminal nerve. The next day, she was referred to the hospital due to multiple infarctions in both hemispheres and cerebellar hemispheres. Both cases had herpes zoster eruptions at the time of stroke onset, but never had risk factors for cerebral infarctions such as hypertension, diabetes, and hyperlipidemia. Therefore, both cases were diagnosed as cerebral infarctions associated with varicella zoster virus. We speculated that varicella zoster virus, which latently infects ganglia, infected vascular endothelial cells, caused vasculitis, and finally caused cerebral infarctions.

An 81-year-old woman who developed herpes zoster infection that involved the area from her right shoulder to her forearm visited our department ; she was hospitalized because of severe pain. Her right upper limb movement had been compromised since admission ; however, accurate evaluation was difficult because of the severe pain. The pain considerably reduced by day 5 under treatment with intravenous acyclovir 500 mg/day, sulbactam/ampicillin 1125 mg/day, and oral acetaminophen 1200 mg/day and pregabalin 50 mg/day. However, her right limb motor paralysis persisted. Neurological examination revealed muscle weakness corresponding to the C5 and C6 regions, and magnetic resonance imaging identified high T2 signal in the right brachial plexus neuritis. She was diagnosed with right brachial plexopathy secondary to herpes zoster infection. After incrustation of all the vesicles and blisters on day 9, she was transferred to our neurology department. Two sessions of steroid pulse therapy (methylprednisolone 1 g/day for 3 consecutive days) and daily oral prednisolone 45 mg/day (1mg/kg/day) failed to achieve any improvement in terms of her right limb motor paralysis. However, intravenous immunoglobulin administered from day 28 effectively reduced her symptoms. After the administration of additional steroid pulse therapy, oral prednisolone was tapered from day 45, and she was discharged from our hospital on day 54. Herpes zoster infection is common ; however, recently, the number of cases, particularly those among elderly subjects, is increasing. Live-attenuated and subunit vaccination of herpes zoster are covered by national insurance since March 2016 and March 2018, respectively, for people aged ≥ 50 years ; however, this facility has not been utilized extensively thus far. In order to reduce the number of serious neuro-related complications of herpes zoster that could potentially affect a patient's daily routine activities, affirmative herpes zoster vaccinations for the elderly are recommended.

A 54-year-old woman with no underlying disease presented with a subcutaneous mass in the neck after dental therapy. She was treated for inflammation of the submandibular gland, and the symptoms became less severe. However, thereafter, her symptoms exacerbated. She visited our department 9 months after symptom onset. She had a red mass on the neck. We made an incision in the mass and found green granules sized 1-2 mm in the pus. We established a diagnosis of actinomycosis in the neck based on the histopathological examination. We performed treatment with antibiotics, incision, and resection.

Trichophyton verrucosum is one of the zoophilic dermatophytes that usually infect cattle. When it infects human beings when they have skin contact with cattle, the infection is accompanied by an inflammatory reaction. Pustules coalesce to form elevated erythematous plaques without annular erythema. These unusual clinical features are different from those of common ringworm and may lead to delayed diagnosis. We have experienced two cases wherein steroid ointments were used for different diagnoses, and the clinical courses of the disease were prolonged. Case 1 was that of a 50-year-old male dairy farmer, who had cows, and visited our hospital because of erythema with pustules on his left forearm. He was diagnosed with inflammatory ringworm and was treated with 125 mg/day of itraconazole and neticonazole ointment for 9 weeks. Case 2 was that of a 7-year-old boy. His mother worked in a place with a cowshed. He and his mother did not report any contact with cattle. After he injured his head by hitting it against the doors of the sink shelf, he developed an ulcer on his right temporal area. The ulcer enlarged rapidly and was covered with yellow crusts. The hair strands around the lesion were easily pulled, and hyphae were observed in the hair shafts. He was diagnosed with kerion celsi and was treated with oral terbinafine hydrochloride (60 mg/day) for 4 weeks with no positive outcome. He was then treated with itraconazole (150 mg/day) for 16 weeks without recurrence. Trichophyton verrucosum was identified in the cultures from both patients.

Dr. Chih-Hung Lee (also known as Abel Lee) is currently the Chair and Professor in Department of Dermatology, Kaohsiung Chang Gung Memorial Hospital (KCGMH) and Chang Gung University (CGU) College of Medicine in Kaohsiung, Taiwan. He is also the Chief Editor of Dermatologica Sinica, the official journal of Taiwanese Dermatological Association (TDA) and Taiwanese Society for Investigative Dermatology (TSID). He served as Board Director of TDA from 2015 to 2018 and Executive Director of TSID from 2012 to 2018. He has served as the Executive Director of TDA and the Secretary General of TSID since 2018.