A Case of Refractory Vernal Keratoconjunctivitis Showing Improvement after the Administration of Upadacitinib for the Treatment of Atopic Dermatitis.

Vernal keratoconjunctivitis is a persistent allergic ocular disease predominantly mediated by the T-helper 2 lymphocyte-associated immune response. The standard therapeutic approaches for vernal keratoconjunctivitis include topical corticosteroids and immunosuppressive eye drops. However, managing vernal keratoconjunctivitis with only topical treatments becomes challenging during seasonally exacerbated periods. Systemic treatments such as oral corticosteroids or cyclosporine may be alternative options. Recently, dupilumab's efficacy in refractory vernal keratoconjunctivitis treatment has been documented. Here, we report a case of refractory vernal keratoconjunctivitis coexisting with atopic dermatitis that rapidly improved after upadacitinib administration. An 18-year-old Japanese woman presented with atopic dermatitis, vernal keratoconjunctivitis, and hay fever. In winter, the patient experienced widespread erythema and escalated itching, leading to significant discomfort and insomnia. Owing to the difficulty in maintaining her current regimen, upadacitinib (15 mg), a Janus kinase inhibitor was initiated. After upadacitinib administration, the treatment-resistant vernal keratoconjunctivitis and erythema improved. Upadacitinib is beneficial in severe cases of atopic dermatitis. Consequently, in our case, upadacitinib may offer therapeutic benefits for refractory vernal conjunctivitis by improving the T-helper 1/2 type immune response, autoimmunity, and oxidative stress. To our knowledge, this is the first report suggesting the potential utility of upadacitinib in managing severe vernal conjunctivitis.

Additional effect of excimer light therapy in patients with psoriasis under other therapies.

Excimer light is an effective therapy for psoriasis resulting in faster clearance and a longer remission. We studied its additional effect in patients with psoriasis under other therapies. Subjects were composed of 261 patients with psoriasis, all of which were treated with topical application of steroid and vitamin D mixed ointment. Other therapies were composed of apremilast and biologics. PASI 100 rate were evaluated until 12 months after the start of its therapy. PASI 100 rate was elevated from 13 patients (5.0%) to 34 patients (13.0%, P < 0.01). Twenty-one of 63 patients (33.3%, P < 0.01) not reaching PASI 100 reached it after excimer light therapy. The addition of excimer light therapy in each treatment showed no significant difference compared with that before addition. Irradiation amount in patients with guselkumab (822 ± 259 mJ) was significantly smaller that with excimer only (1370 + 731 mJ) and that with IL-17 (1747 ± 749 mJ). In addition, irradiation amount in patients reached PASI-100 in Guselkumab (717 ± 75 mJ) which was significantly smaller that in the excimer only group (1530 ± 450 mJ). Additional effect of excimer light therapy in psoriasis, especially in patients with guselkumab, was speculated.

Palisading granuloma presenting in a patient with systemic lupus erythematosus.

A patient with systemic lupus erythematosus who developed a distinctive nodular eruption demonstrating typical features of palisading granuloma is presented herein. A 60-year-old woman was admitted complaining of an elastic-hard, indurated nodule on the right dorsal aspect of the metacarpophalangeal joint of her third finger with a history of several years. She was successfully treated for her lupus nephritis with oral predonisolone. She had experienced erythema on her cheeks after sun exposure and polyarthralgia for a decade. Laboratory examination revealed positive results for antinuclear antibody and rheumatoid factor. Peripheral blood cell counts showed leukocytopenia and lymphocytopenia. Results of hand X-ray were unremarkable. Histological examination of the skin biopsy specimen from the nodule revealed a structure composed of a central area of fibrinoid necrosis, surrounded by a middle zone of palisading cells and an outer zone of chronic lymphocyte infiltrate. These findings led us to the histological diagnosis of palisading granuloma. She was diagnosed as having systemic lupus erythematosus complicated with a rheumatoid nodule. She is currently under treatment with cyclophosphamide (50 mg/day) without exaggeration of her systemic lupus erythematosus and nodule.

Relation between elevated high-sensitivity C-reactive protein and anti-mitochondria antibody in patients with systemic sclerosis.

Systemic sclerosis (SSc) is a systemic connective tissue disease of unknown etiology which presents immunological, vascular and connective tissue abnormalities. C-reactive protein (CRP) has been used for the evaluation of inflammation in patients with infection and inflammatory diseases. Recently, high-sensitivity CRP has been shown to reflect mild and/or moderate inflammation for the prognosis of ischemic heart disease. High-sensitivity CRP was measured for the evaluation of mild and/or moderate inflammation in SSc. Forty SSc patients (male : female, 7:33; age, 16-78 years; mean, 61.9 years) were studied. High-sensitivity CRP was measured with a nephelometric assay. The detection limit was 0.0036 mg/dL, linearity from 0.015-1.5 mg/dL. The distribution of high-sensitivity CRP showed 26 cases (65.0%) low, three cases (7.5%) mild, four cases (10.0%) moderate, four cases (10.0%) high and three cases (7.5%) highest. The occurrence rate of anti-mitochondria antibody in high-sensitivity CRP elevated SSc patients (8/14, 57.1%) was significantly elevated compared with that of high-sensitivity CRP low SSc patients (3/26, 11.5%) (P < 0.01). These results led us to the conclusion that elevated high-sensitivity CRP shows relation to the occurrence of anti-mitochondria antibody.

Detection of mucosal human papilloma virus DNA in bowenoid papulosis, Bowen's disease and squamous cell carcinoma of the skin.

Human papilloma virus (HPV) is known to be an etiologic agent for benign warts of the skin. Recently, HPV have been detected in malignant skin and mucosal diseases suggesting that HPV infection can induce malignant skin tumors. In the present study, we examined the presence of mucosal HPV DNA in normal tissue, Bowen's disease (BD), Bowenoid papulosis (BP) and squamous cell carcinoma (SCC) of the skin. We detected the HPV DNA with polymerase chain reactions, and identified the type by DNA sequencing. In the results, we detected HPV DNA in none of the 17 normal controls, two of the three BP (66.7%), one of the 21 BD (4.8%), and six of the 26 SCC of the skin samples (23.0%). The occurrence rates of HPV in BP and SCC were significantly elevated compared to that of normal controls (P < 0.01 and P < 0.01, respectively). In addition, the occurrence rate of HPV in BP was significantly elevated compared to that of BD (P < 0.05). The reproducibility was confirmed with a polymerase chain reaction (PCR) with another primer pair. Of the two cases of BP with positive HPV DNA, one case showed HPV 31 and the other case HPV 16. The case of BD with positive HPV DNA showed HPV 31. Of the six cases of SCC with positive HPV DNA, one case showed HPV 16, another case HPV 34, and the other four cases HPV 31. These results showed that mucosal HPV, including HPV 31 and 16, could be detected in SSC of the skin. Mucosal HPV, not only the epidermodysplasia verruciformis type, appear to induce malignant skin tumors.

The involvement of immunoglobulin E isotype switch in scleroderma skin tissue.

BACKGROUND: The involvement of mast cell, which is activated by immunoglobulin E (IgE), has been reported in the formation of systemic sclerosis (SSc) abnormality. IgE is generated with isotype switch. During isotype switch, switch circles resulting from direct mu to epsilon, or from sequential mu to gamma via epsilon switching will be created. OBJECTIVE: We studied whether switching occurs in SSc. METHODS: We used nested polymerase chain reaction to analyze the S fragments from switch circles. Fifty-two patients with SSc, and 62 healthy women were studied. RESULTS: Neither of 62 normal skin tissues showed direct switch, nor sequential switch. Neither of seven normal whole blood cells showed direct switch, nor sequential switch. In 52SSc skin tissues, three (5.8%) showed direct switch, and two (3.8%) showed sequential switch. As a result, five (9.6%) of SSc skin tissue showed immunogobulin E class switch. These results were confirmed by DNA sequencing. CONCLUSION: These results demonstrated that isotype switch to the epsilon locus achieved by direct and/or sequential switch are involved in SSc skin.

Quantitative echographic analysis of photochemotherapy on systemic sclerosis skin.

Systemic sclerosis (SSc) is a connective tissue disease of unknown etiology, in which development of fibrosis, vascular insufficiency and inflammatory processes are prominent in the skin as well as in other organs. We studied the effect of photochemotherapy with quantitative echography in SSc. Dermal echo intensity and dermal thickness was measured using high-frequency dermal echography before and after therapy. The dermal echo intensity after photochemotherapy (33.51+/-9.34) significantly increased than that before therapy (21.23+/-6.00) (P < 0.01), while dermal thickness (1.20+/-0.20) significantly decreased than that before therapy (1.38+/-0.18) (P < 0.05). Photochemotherapy was more likely to improve dermal edema, not fibrosis, because echo intensity after treatment was significantly elevated with that before treatment in patients with edema. Quantitative echographic analysis was concluded to be a reliable method in evaluating the change of skin edema in SSc.

Squamous cell carcinoma of the penis in a man with a human papilloma virus 31 infection.

We report a 51-year-old man with squamous cell carcinoma (SCC) on his penis. He was surgically treated for his phimosis when he was 20 years old. He presented with an indurated nodule on the tip of his penis. The tumor was treated with partial penectomy and standard inguinal lymphadenectomy. Histological examination revealed that the tumor was a well-differentiated type of SCC. A polymerase chain reaction was performed to detect human papilloma virus (HPV) DNA. The result revealed the presence of HPV in the SCC. The results of sequencing analysis showed that the DNA was HPV 31.

Different effect of oral cyclosporine therapy and oral antihistamine therapy on serum high-sensitivity C-reactive protein level and thymus and activation-regulated chemokine level in atopic dermatitis in older children and adulthood.

BACKGROUND: Many patients with atopic dermatitis (AD) are treated with oral cyclosporine or antihistamine therapy in clinical practice. OBJECTIVE: To evaluate the effectiveness of oral cyclosporine and antihistamine therapy on clinical and laboratory findings in patients with AD. SUBJECTS AND METHODS: Twenty-five patients with AD (male-female = 11 : 14, age 16-42 years old, mean 26.2 years old) were treated with oral cyclosporine therapy. Twenty-three patients with AD (male-female = 10 : 13, age 15-32 years old, mean 24.2 years old) were treated with oral antihistamine therapy. Laboratory findings including high-sensitivity C-reactive protein (CRP) and thymus and activation-regulated chemokine (TARC) were statistically studied. RESULTS: Serum TARC level after oral cyclosporine therapy (1013 ± 883 pg/ml) was significantly decreased compared to before therapy (38 194 ± 4678 pg/ml; P < 0.02). Basophil counts in peripheral blood after the therapy (49.7 ± 26.4 × 10(-3) cells/µl) were more significantly increased than before therapy (41.1 ± 16.7 × 10(-3) cells/µl; P < 0.05). Serum high-sensitivity CRP level after antihistamine therapy (0.09 ± 0.08 mg/ml) was significantly decreased compared to before therapy (0.13 ± 0.12 mg/ml; P < 0.05). Basophil counts in peripheral blood after the therapy (33.4 ± 16.2 × 10(-3) cells/µl) were more significantly decreased than before therapy (41.5 ± 23.3 × 10(-3) cells/µl; P < 0.01). CONCLUSION: Different effects of oral cyclosporine therapy and oral antihistamine therapy to serum high-sensitivity CRP level, TARC level, and peripheral blood basophils in adult patients with AD were shown. A combination of these two therapies may be more effective for the treatment of AD in adults.

Polymorphism of the vitamin D(3) receptor in patients with psoriasis.

1,25-Dihydroxyvitamin D is the biologically active form of vitamin D for the treatment of skin eruptions in patients with psoriasis. 1,25-(OH)(2)D(3) elicits its action on skin eruptions through the vitamin D receptor (VDR). Allelic frequencies of VDR were studied in 86 normal subjects and 50 patients with psoriasis. Genomic DNA was extracted from peripheral blood leukocytes and the VDR gene was amplified using a heminested polymerase chain reaction (PCR). The products were digested with respective restriction enzymes ApaI, TaqI and BsmI. The restriction fragment length polymorphisms (RFLP) were coded as Aa, Tt or Bb. The frequencies of ApaI, BsmI and TaqI RFLP genotypes in psoriasis patients showed no significant differences compared with normal controls. The frequency of the AA genotype was significantly higher in pustulosis palmaris et plantaris patients than in psoriasis vulgaris patients ( P<0.05), and in psoriasis vulgaris patients than in psoriasis pustulosa patients ( P<0.01). In patients with psoriasis, the levels of serum alanine 2-oxoglutarate aminotransferase (ALT) were significantly higher in patients with the AA genotype (54.0+/-22.0 IU/l, n=4) than in those with the aa genotype (24.0+/-15.9 IU/l, n=27; P<0.02). The distribution of ApaI, BsmI, TaqI RFLP VDR genotypes showed no significant relationship to the PASI score, serum aspartate 2-oxoglutarate aminotransferase or triglyceride levels, or age at onset. These results show that the VDR genotype contributes to the liver dysfunction in patients with psoriasis, although no correlation was found between VDR genotype and the skin eruptions of psoriasis.

Leg ulcer presenting in a patient with congenital afibrinogenaemia.

Congenital afibrinogenaemia is a rare hemorrhagic disorder characterized by the absence of fibrinogen. We report a case of congenital afibrinogenaemia presented with leg ulcer. A 30-year-old man presented with a history of prolonged bleeding from birth. His parents are cousins. He repeatedly showed haematoma after traumas on his leg. He was diagnosed as having congenital afibrinogenaemia because of plasma fibrinogen deficiency. Because his leg ulcer gradually increased in size, he was admitted to our department for treatment. Laboratory examinations revealed prolonged bleeding time, prolonged coagulation time, prolonged prothrombin time, prolonged activated partial thromboplastin time and plasma fibrinogen was not measurable. Histological examination revealed hyperkeratosis, acanthosis and severe fibrotic change in the whole dermis. Severe hemosiderin deposit was found in the middle dermis. His leg ulcer cured 2 months after the beginning of fresh frozen plasma administration (FFP), but recurrence of the leg ulcer after FFP treatment was found. This is the second reported case of congenital afibrinogenaemia presented with leg ulcer.

Entero-Behçet's disease coexisting with long-term epilepsy and schizophrenia-like symptoms.

Entero-Behçet's disease coexisting with long-term epilepsy and schizophrenia-like symptoms is presented. A 43-year-old woman presented with repeatedly occurring aphthous stomatitis for several years. She had been treated for absence seizures, epilepsy and schizophrenia since she was 9 years old. She presented with multiple aphthous stomatitis on her gingiva, erythema nodosum-like symptoms on the right lateral aspect of her leg and genital ulcers on her perianal area. She also showed polyarthritis. Laboratory examinations revealed elevated C-reactive protein, elevated neutrophil counts, decreased serum Fe and elevated serum Cu. Histological examination showed perivascular neutrophil and mononuclear cell infiltrates and eosinophilic change of the vessel wall in the lobules of subcutaneous fat tissue. Six weeks after the oral prednisolone therapy, she showed resolution of aphthous stomatitis, folliculitis-like eruption and genital ulcer. She experienced severe abdominal pain after the start of treatment of Behçet's disease. Plain computed tomography revealed edematous change in the appendix, and ascending and transverse colon. These results led to the diagnosis of entero-Behçet's disease acute exaggeration. Treatment with infliximab (300 mg/once) was started. Eight weeks after the start of infliximab, her abdominal pain disappeared and C-reactive protein decreased, followed by the successful change to adalimumab infusion therapy.

Dermoscopic detection of nail fold capillary abnormality in patients with systemic sclerosis.

The diagnosis of systemic sclerosis (SSc) is often difficult. The purpose of the present study was to find the distribution of nail fold capillary abnormality in SSc. Sixty-two patients with SSc (male : female = 7:55, age 21-86 years, mean 60.1) admitted to the outpatient clinics were studied. Eighteen age- and sex-matched normal subjects, 28 patients with systemic lupus erythematosus (SLE) and 10 with dermatomyositis (DM) were also studied. Nail fold capillary loops were observed under immersion oil at a magnification of ×40 with a light microscope. Dilated capillaries, nail fold bleeding and avascular areas were found by dermoscopic observation. The distribution of dilated capillaries, nail fold bleeding and avascular areas in normal controls showed in one (5.6%), one (5.6%) and four cases (22.2%), respectively. The distribution of dilated capillaries, nail fold bleeding and avascular area in SSc patients showed in 27 cases (43.5%), eight cases (12.9%) and 16 cases (25.8%), respectively. The distribution of dilated capillaries and/or nail fold bleeding in SSc patients (29/62, 46.8%) was significantly elevated than that of normal controls (2/18, 11.1%) (P < 0.01). The distribution of overall abnormality in SSc (30/62, 48.4%) showed no significant difference compared with that of normal controls (4/18, 22.2%). Sensitivity and specificity for dilated capillaries and/or nail fold bleeding and overall nail fold abnormality in SSc patients compared with normal controls was calculated as 40.8% and 93.5%, 34.8% and 88.2%, respectively. Dermoscopic observation of dilated capillaries and/or nail fold bleeding is a sensitive and specific method for the detection of SSc.

Serum interleukin-6 level is reflected in elevated high-sensitivity C-reactive protein level in patients with systemic sclerosis.

Systemic sclerosis (SSc) is a systemic connective tissue disease of unknown etiology which presents immunological, vascular and connective tissue abnormalities. Serum interleukin (IL)-6 has been reported to be elevated in patients with SSc. Clinical and laboratory findings affecting the elevated level of high-sensitivity C-reactive protein (hs-CRP) were studied in patients with SSc. Clinical and laboratory findings also included serum IL-6 level. Thirty-nine SSc patients (male : female = 7:32, age 19-84 years, mean 62.6 years) were studied. hs-CRP was measured with a nephelometric assay. Serum IL-6 level was measured by enzyme-linked immunosorbent assay. The distributions of hs-CRP showed that 18 cases (46.2%) were not elevated (<0.07 mg/dL), but 21 cases (53.8%) were (≥0.07 mg/dL). Alkaline phosphatase and IL-6 in SSc patients with elevated hs-CRP (291 ± 95 U/L, 3.23 ± 2.74 pg/mL) were significantly more elevated than those in not elevated patients (221 ± 75 U/L, 1.53 ± 1.12 pg/mL) (P < 0.02, P < 0.01). The correlation between hs-CRP level and IL-6 level in SSc patients was 0.687 (P < 0.001). In conclusion, elevated serum IL-6 levels are reflected in elevated hs-CRP levels in SSc patients.

Response to oral cyclosporine therapy and high sensitivity-CRP level in chronic idiopathic urticaria.

BACKGROUND: Chronic idiopathic urticaria (CIU) is often resistant to common treatment of uriticaria. OBJECTIVE: To find out clinical and laboratory findings affecting the response of oral cyclosporine therapy in CIU. SUBJECTS AND METHODS: The response of oral cyclosporine therapy in 15 patients with CIU (male:female = 5:10, age 16-60 years old, mean 40.0 years old) was studied. Cyclosporine trough level was measured with an enzyme-multiplied immunoassay, and high sensitivity-CRP was measured with a nephelometric assay. The relation between high sensitivity-CRP level and clinical and laboratory findings in CIU was also studied. RESULTS: All the 15 CIU patients responded to oral cyclosporine therapy. High sensitivity-CRP levels before the start of therapy were elevated in nine of 15 CIU patients. The distributions of treatment duration and basophile leukocytes counts in elevated high sensitivity-CRP patients (8.7 +/- 1.3 months, 0.20 +/- 0.05%) were significantly shorter and elevated than those in patients showing no elevation (22.7 +/- 1.7 months, 0.40 +/- 0.05%) (P < 0.05, P < 0.05), respectively. No other clinical and laboratory findings between patients with elevated and not elevated high sensitivity-CRP showed any significant differences. CONCLUSION: Chronic idiopathic urticaria patients with elevated high sensitivity-CRP showed good response to oral cyclosporine therapy.

Combinational effect of low-dose oral corticosteroid and mizoribine for ulcerative colitis in a patient with systemic sclerosis.

The combinational effect of oral corticosteroid and mizoribine for ulcerative colitis is presented in a patient with systemic sclerosis (SSc). A 64-year-old woman came to our clinic complaining of a 30-year history of Raynaud's phenomenon. She had past history of ulcerative colitis with the continued medication of mesalazine without success. She was presented with sclerodactyly and finger joint swelling. She also showed epigastric discomfort. Laboratory study showed positive anti-nuclear antibody and positive anti-centromere antibody. Histological examination showed mild perivascular mononuclear cell infiltrates in the whole dermis and increased deposition of collagen fibers in the middle and lower dermis. Chest X-ray film showed mild bibasilar pulmonary fibrosis. An upper gastrointestinal series study showed reflux esophagitis and atrophic gastritis. These findings led to the diagnosis of systemic sclerosis (limited type) complicated with ulcerative colitis. Treatment with oral corticosteroid (5 mg/day) and mizoribine (150 mg/day) in the morning was started. She showed remarkable improvement for sclerodactyly and lower intestinal bleeding stopped after 6 months. She is under the same treatment without exaggeration and adverse effect of the drug until now.