Arteriosclerosis Derived from Cutaneous Inflammation Is Ameliorated by the Deletion of IL-17A and IL-17F.

The skin is one of the major immune organs producing large amounts of proinflammatory and inflammatory cytokines in response to internal or exogenous stimuli, inducing systemic inflammation in various internal organs. In recent years, organ damage associated with inflammatory skin diseases such as psoriasis and atopic dermatitis has received increasing attention, and vascular disorder such as arteriosclerosis is one of the serious complications of chronic inflammatory skin diseases. However, the detailed mechanism of arteriosclerosis in dermatitis and the role of cytokines have not been clarified so far. In the current study, using a spontaneous dermatitis model, we investigated the pathophysiology of arteriosclerosis and the treatment option for inflammatory skin conditions. We employed spontaneous dermatitis model mice overexpressing human caspase-1 in the epidermal keratinocyte (Kcasp1Tg). The thoracic and abdominal aorta was investigated histologically. GeneChip and RT-PCR analysis were performed to measure the changes in mRNA levels in the aorta. To elucidate the direct effect on the artery by major inflammatory cytokines, endothelial cells, vascular smooth muscle cells, and fibroblast cells were co-cultured with several cytokines, and mRNA expression levels were measured. In order to observe the efficacy of IL-17A/F in arteriosclerosis, cross-mating with IL-17A, IL-17F, and IL-17A/F deficient mice was performed. Finally, we also measured snap tension in the abdominal aorta in WT, Kcasp1Tg, and IL17A/F-deficient mice. Kcasp1Tg showed a decrease in the diameter of the abdominal aorta compared to wild-type mice. mRNA levels for six genes including Apol11b, Camp, Chil3, S100a8, S100a9, and Spta1 were increased in the abdominal aorta of Kcasp1Tg. Some of the above mRNA levels were also increased in the co-culture with major inflammatory cytokines, IL-17A/F, IL-1ß, and TNF-α. Dermatitis improved and mRNA levels were partially ameliorated in Kcasp1Tg with IL-17A/F deletion. Arterial fragility was also evidenced in the inflammatory model, but arterial flexibility was revealed in the IL-17A/F deletion model. Severe dermatitis is closely related to secondary arteriosclerosis caused by the persistent release of inflammatory cytokines. The results also proved that treatment against IL-17A and F may ameliorate arteriosclerosis.

Septic pulmonary embolism and subsequent bilateral pneumothorax in patients undergoing chemoradiotherapy for head angiosarcoma: An autopsy case report and literature review.

RATIONALE: Septic pulmonary embolism (SPE) and subsequent pneumothorax are rare but serious conditions. We report a case of SPE and pneumothorax caused by central venous port (CV port) infection. PATIENT CONCERNS: A 73-year-old woman, who underwent chemoradiotherapy for a head angiosarcoma and a CV port placement, presented with general malaise and myalgia. DIAGNOSIS: A laboratory examination showed high levels of inflammatory markers. Chest computed tomography showed fluid collection around the CV port and multiple ground-glass opacities and nodular shadows in the bilateral lung field. She was admitted with a diagnosis of SPE due to CV port infection. The port was removed, and antibiotic administration was initiated; however, she was intubated because of refractory septic shock. Methicillin-susceptible Staphylococcus aureus was detected in the blood and pus around the port site. INTERVENTIONS: Her respiratory status did not improve despite recovering from septic shock, and radiologic findings showed a left pneumothorax and exacerbation of SPE on day 9. Her condition was judged ineligible for surgery for pneumothorax, and chest tube thoracostomy was continued. OUTCOMES: Air leaks persisted after chest tube thoracostomy, and her respiratory status did not improve despite ventilator management and recruitment maneuvers. Moreover, a right pneumothorax developed on day 19. Her respiratory status gradually worsened, and she died on day 21. Autopsy showed multiple cavitary lesions in the bilateral lungs and emboli containing organization and inflammatory cells that obstructed the pulmonary arterioles. LESSONS: This case indicates that CV port-related infections are infrequent and difficult to diagnose; understanding the clinical features of SPE is important because of its high mortality rate; and pneumothorax secondary to SPE is a rare but serious condition and is difficult to treat during ventilator management.

Skin graft fixation with negative pressure wound therapy with instillation and dwelling (NPWTi-d) for contaminated complex wounds of the extremities.

Objective: Negative Pressure Wound Therapy (NPWT) is increasingly being used as a major method of skin graft dressing and fixation. Negative Pressure Wound Therapy with Instillation and Dwelling (NPWTi-d) further enhances wound care over regular NPWT. However, only a few reports have been made on its use for skin graft fixation due to concerns of graft maceration or detachment. We used NPWTi-d to fix skin grafts for 4 cases of severely contaminated complex posttraumatic wounds. Methods: The age ranged from 37 to 72 years, and included trauma of the lower leg, forearm dog bite and incomplete amputations of the upper arm and hand respectively. The mean instillation saline volume per wound size was 0.21 ml/cm2 and the dwelling time reduced to 3 min. The NPWTi-d skin graft fixation was removed after about a week. Results: All the grafts healed well and no complications such as infection or contracture were observed. Follow-up time was 1 -8 months. Conclusions: NPWTi-d may be a useful option for fixing skin grafts particularly in contaminated wounds with a high risk of infection.

Three Cases of Lymphocytic Infiltration of the Eyelid.

Lymphocytic infiltration of the skin (LIS), first reported by Jessner and Kanof in 1953, is a disease of unknown etiology characterized by erythematous papules and plaques on the head, neck, and upper back and histopathological findings of a normal epidermis with underlying lymphocytic infiltration of the reticular dermis without mucin deposition. A 69-year-old man and a 21-year-old woman presented with edematous indurative erythema of the left upper eyelid. Lymphocytic infiltration of the dermis with CD4+ T cell predominance was noted on biopsy. A 68-year-old man presented with a four-year history of recurrent edematous indurative erythema of the right upper eyelid that extended up to the right cheek. Predominantly dermal infiltration of CD8+ T lymphocytes was found on biopsy. We treated all three patients with 8-16 mg of methylprednisolone daily, and the erythema and induration improved. CD4+ T cells were predominant in the acute phase (patients 1 and 2), whereas CD8+ T cells were predominant in the chronic phase (patient 3). CD8+ T cells may be involved in LIS recurrence. Lymphocytic infiltration of the eyelid may be associated with isolated circumscribed, edematous, indurative, colorless lesions that are responsive to daily low-to-middle doses of oral methylprednisolone.

Palisaded neutrophilic granulomatous dermatitis, interstitial granulomatous dermatitis and IgA vasculitis associated with incomplete Sjögren's syndrome.

Palisaded neutrophilic granulomatous dermatitis (PNGD) and interstitial granulomatous dermatitis (IGD) are rare granulomatous disorders. Differential diagnosis of PNGD and IGD is often difficult, but both conditions occasionally exist together. We report here the first potential overlapping case of PNGD, IGD, and Immunoglobulin A (IgA) vasculitis associated with incomplete Sjögren's syndrome. An 81-year-old woman who had been followed up for interstitial pneumonia and incomplete Sjögren's syndrome was referred to our clinic. She had multiple erythematous plaques and nodules on her entire body and purpura on her legs. Biopsied specimens showed granuloma formation with neutrophilic infiltration and degenerated collagen fibers in the center. In addition, interstitial granuloma and so-called "floating sign" in the periphery and leukocytoclastic vasculitis were noted. Elastica-van Gieson staining revealed phagocytosis of elastic fibers by multinucleated giant cells around the granulomas. Direct immunofluorescence showed IgM, IgA, and C3 deposition in vascular walls. We made a diagnosis of an overlap syndrome of PNGD, IGD, and IgA vasculitis in a background of incomplete Sjögren's syndrome. No such case has been previously reported. The pathogenesis of the present case may be associated with Sjögren's syndrome.

Verruca Vulgaris and Seborrheic Keratosis Exacerbated by Immunosuppression.

Verruca vulgaris is an infectious disease caused by the human papillomavirus and characterized by hyperkeratotic papules or plaques with a clear boundary. Seborrheic keratosis is a commonly encountered lesion on the face, trunk, or extremities and is described as seborrheic verruca because of its clinical similarity to warts; furthermore, it is occasionally associated with immune suppression, especially in cases of Leser-trélat syndrome. Although these diseases are frequently found in healthy individuals, they typically show a good response to cryotherapy. However, cases in immunosuppressed patients are intractable to therapy. Overall immune status is evaluated via complete blood count (CBC); however, white blood count does not show the exact immune ability, and NK cell activity is often decreased in cases of malignancy. Here, we present two cases of exacerbated verruca vulgaris and seborrheic verruca observed in patients with malignancy. Although the patients seemed to be in good condition and had a normal CBC, immunosuppression was suspected based on the degree of skin rashes. NK cell activity was decreased in both patients, and both cases had malignancy. The measurement of NK cell activity may be a useful approach to evaluate immune status.