Chronic superficial pyoderma of the face: an unusual male case of rosacea fulminans

A 62-year-old Japanese male developed acneiform papules on the face in November of 2002. The eruptions progressed to exudative erythema with central necrosis, and then to thick-crusted superficial abscesses in a short period. The shallow ulcers exposed by removal of the crusts and abscesses immediately re-epithelized without leaving scars. The histology of the eruption was a dense infiltration of neutrophils associated with granulomatous changes in the upper to middle dermis. Histology of the tiny white particles in the abscess showed an irregularly proliferated mass of keratinocytes including accumulated neutrophils. The skin lesions resisted intravenous injection of antibiotics but responded to systemic administration of a corticosteroid agent. Colchicine did not work well, but the additional administration of etretinate was effective. The patient is currently receiving combined therapy with prednisolone and etretinate, but eruptions are still episodically observed. We diagnosed this case as an unusual male case of rosacea fulminans.     

肛周坏疽性脓皮病合并糖尿病1例

患者男,80岁。肛周皮疹伴疼痛3个月。患2型糖尿病3年。皮损组织病理示:溃疡处表皮缺如,真皮中浅层大量中性粒细胞浸润,其间血管纤维束样变性,中性粒细胞浸润;皮损边缘表皮增厚水肿,血管周围中性粒细胞浸润;未见肿瘤细胞。诊断:坏疽性脓皮病。     

Three cases of Darier's disease in a family showing marked heterogeneous clinical severity.

We report a Japanese family in which two sisters and their mother with Darier's disease showed apparent heterogeneous clinical severity. The elder sister had extensive skin lesions typical of Darier's disease on the scalp, face, neck, axillae and chest. The skin lesions of the younger sister were less severe. The mother had had skin lesions due to Darier's disease with moderate severity since her teenage years. The lesions had gradually involuted as she grew older, leaving only postinflammatory pigmentation around the neck. Thus, spontaneous remission of skin lesions, rare in Darier's disease, and heterogeneous clinical severity between and within generations were noted in this family.     

Sweet's syndrome associated with Mycobacterium avium infection

A 68-year-old woman presented with a 3-month history of nontender, erythematous nodules on the right side of the neck. Subsequently, tender, circinate erythematous plaques appeared on the limbs, accompanied by peripheral leucocytosis. A biopsy specimen obtained from an erythematous plaque revealed diffuse infiltration of neutrophils in the dermis. Treatment with prednisolone improved the erythematous lesions, but upon tapering of prednisolone, numerous areas of indurated erythema with pustules recurred on the face and back accompanied by high fever. Computed tomography of the lung revealed multiple lesions. A smear of gastric juice contained acid-fast bacilli that were identified as Mycobacterium avium by DNA–DNA hybridization. Treatment with multiple antibiotics did not result in a favourable response of the M. avium infection, and dome-shaped, subcutaneous abscesses developed on the limbs and trunk. Sweet's syndrome may thus occur in association with nontuberculous mycobacterial infection.     

Kikuchi's disease (histiocytic necrotizing lymphadenitis) with cutaneous involvement

We report a case of Kikuchi's disease (histiocytic necrotizing lymphadenitis) in a 22-year-old Japanese man who presented with cervical and axillary lymphadenopathy and who developed edema of lips with desquamation and erosions and transient indurated erythematous papules on the face, neck and upper extremities. A lymph node biopsy specimen showed the typical necrotizing lymphadenitis of Kikuchi's disease. A skin biopsy specimen showed a dense, lymphohistiocytic, superficial, deep perivascular, and interstitial infiltrate, papillary dermal edema, and abundant nuclear debris with a conspicuous absence of neutrophils, paralleling the nodal histology of Kikuchi's disease. CD68 immunohistochemistry showed many plasmacytoid monocytes. Oral corticosteroid (prednisolone 40 mg) therapy improved the skin lesions and other clinical symptoms. Lip involvement by Kikuchi's disease has not been reported, and should be included as one of the possible cutaneous manifestations of Kikuchi's disease.     

Successful treatment of adolescent pemphigus vulgaris by immunoadsorption method.

A 15-year-old girl with pemphigus vulgaris did not respond to oral administration of prednisolone at 45 mg/day. The skin and oral mucous membrane lesions recurred after effective treatments with methylprednisolone pulse therapy and combination therapy with prednisolone and cyclosporine. The finally successful treatment involved eleven cycles of immunoadsorption using a tryptophan column and administration of a moderate dose of prednisolone. Serum gamma-globulin level and anti-intercellular antibody titer decreased from 1.08 g/dl to 0.5 g/dl and 1:320 to 1:20, respectively. She has been well controlled with 21.5 mg/day prednisolone for 8 months after the final adsorption. Considering the physical, mental and social situation of adolescent student patients, immunoadsorption is a highly preferable choice among a variety of treatment modalities for pemphigus vulgaris because it makes the term of hospitalization shorter and avoids undesirable side effects from initial high dose corticosteroids.     

Infectious urticaria with purpura: a mild subtype of urticarial vasculitis?

Urticaria is characterized by transient wheals. We report here five cases with long-lasting urticarial lesions persisting for more than 24 hours. Each lesion left purpura after fading. There was no systemic involvement. C-reactive protein and serum levels of complement were elevated or normal. Histologically, marked infiltration by eosinophils and neutrophils with karyorrhexis in the perivascular and intercollagenous spaces was observed, but there was no evidence of vasculitis (venulitis). Skin symptoms were resistant to systemic corticosteroids. In contrast, treatment of underlying bacterial infections resulted in marked improvement of skin lesions. E-selectin, VCAM-1 and ICAM-1 were expressed on endothelial cells. Marked deposition of C3a, C5a, neutrophil elastase and major basic protein in the dermis was observed. These urticarial lesions provoked by bacterial infections seem to lie on the continuum between urticaria and urticarial vasculitis.     

Decreased neutrophil skin infiltration after UVB exposure in patients with polymorphous light eruption

UV radiation, in particular UVB, suppresses the skin immune response. In patients with polymorphous light eruption (PLE) the skin immune response seems activated after UV exposure. Typical PLE skin lesions can occur as early as several hours after UV exposure. In healthy volunteers, neutrophils infiltrate the skin shortly after UV exposure. The kinetics and mechanisms of neutrophil infiltration in the skin of PLE patients after UVB exposure was studied. Skin biopsies at 0, 3, 6, and 18 h were taken from five PLE patients and six healthy controls after irradiation with three minimal erythema dose UVB. Furthermore, neutrophils were isolated from blood of five PLE patients and six healthy controls to test their chemotactic activity. Immunohistochemical analysis showed a significant decreased neutrophil infiltration in PLE skin after UVB irradiation compared with healthy controls (p<0.05). In both healthy controls and PLE patients, after UVB irradiation, ICAM-1 and E-selectin expression on endothelial cells increased at 6 h after irradiation. Blood neutrophil chemotactic response towards IL-8 and C5a, as well as the expression of cell surface markers involved in adhesion and chemotaxis, was not different between PLE patients and healthy controls. In conclusion, PLE is marked by a decreased skin infiltration of neutrophils after UVB irradiation, possibly leading to a diminished neutrophil-induced suppression.     

Scleromyxedema with multiple systemic involvement: Successful treatment with intravenous immunoglobulin

Scleromyxedema is a rare connective tissue disorder characterized by a generalized lichenoid eruption and sclerodermoid induration with histologic features of dermal mucin deposition. A 44‐year‐old man presented with a 3‐year history of generalized progressive skin thickening and sclerosis. He had diffuse skin‐colored to erythematous firm papules coalescing into indurated plaques over his whole body. He had been diagnosed with scleromyxedema from a skin biopsy with monoclonal gammopathy of undetermined significance (MGUS) at another tertiary hospital 3 years earlier. He had been treated with systemic corticosteroids and methotrexate, but his systemic symptoms (dyspnea, dysphagia, skin swelling, and induration) had worsened over the past year, so he visited our clinic seeking further evaluation and management. The patient received high‐dose intravenous immunoglobulin (IVIG) therapy once a month in combination with systemic corticosteroids. After three courses of IVIG, his cutaneous symptoms and dyspnea had improved dramatically. Herein we report a case of scleromyxedema with systemic involvement with significant improvement following IVIG therapy.     

Photo-distributed neutrophilic drug eruption and adult respiratory distress syndrome associated with antidepressant therapy

Drug reactions are well-known complications of antidepressant therapy, often related to photosensitization. Herein is reported a singular case of antidepressant (amoxapine and citalopram) and anxiolytic related (perphenazine) photo-distributed neutrophilic dermatosis and adult respiratory distress syndrome (ARDS). The clinicopathologic findings displayed overlapping features with drug-induced Sweet's syndrome, acute generalized exanthematous pustulosis (AGEP), and so-called sterile neutrophilic folliculitis with perifollicular vasculopathy. Of the three medications, only amoxapine has been associated with AGEP. Treatment with high-dose systemic corticosteroids and cessation of drug therapy was followed by rapid resolution of the cutaneous eruption and respiratory distress. The possibility that neutrophil infiltration of the lung and/or accumulation of neutrophils in the skin and blood served as a source for reactive oxygen species, leading to lung injury and subsequent ARDS, is discussed.     

Adult dermatomyositis with angiopathy and cecum perforation

This previously healthy 43-year-old man was admitted to our hospital with a history of rash, dysphagia and severe myalgia for two months. Physical examination showed prominent edema and erythema over the face and the chest, scattered ulcerations on the trunk, and muscle atrophy most prominent proximally. Serum levels of muscle enzymes were remarkably increased. Two weeks of oral prednisolone therapy (40 mg/day) was not effective, and betamethasone intravenous pulse therapy (3 x 1000 mg) was followed by slight clinical improvement. However, 12 days after pulse therapy, he complained abdominal pain on the right lower quadrant. The surgical findings included peritonitis due to single perforation of the cecum. After operation, cyclosporine therapy was added and over the next 14 month a considerable clinical improvement was noted. Prednisolone was reduced from 80 mg to 10 mg daily. Biopsy specimens from ulcerated+ skin and perforated cecum showed prominent vascular abnormalities: arterial and venous intimal hyperplasia, occlusion of vessels by fibrin thrombi, and lymphocytic infiltration which affected veins of all sizes. The evidence strongly suggests that both skin ulcers and cecum perforation were caused by vasculitis and occlusion of vessels, which often seen in childhood dermatomyositis.     

变应性肉芽肿病一例

报告一例变应性肉芽肿病。患者,女,33岁,过敏性哮喘6年,伴外周血嗜酸性粒细胞增高。2月来出现双下肢丘疹、结节、溃疡伴瘢痕形成,腓肠肌疼痛2周,皮损病理示血管炎和嗜中性粒细胞和嗜酸性粒细胞浸润,确诊为变应性肉芽肿病。     

Photohardening restores the impaired neutrophil responsiveness to chemoattractants leukotriene B4 and formyl-methionyl-leucyl-phenylalanin in patients with polymorphic light eruption

A failure to induce immune suppression after UV exposure has been implicated in the pathogenesis of polymorphic light eruption (PLE). This immunological resistance has been linked to an impaired neutrophil infiltration into the skin following UV exposure. Therapeutic photohardening can restore this abnormal neutrophil infiltration in PLE skin and is thought to be responsible for the prophylactic efficacy. The aim of this study was to elucidate the pathogenic mechanism of the described neutrophil deficiency in PLE. Peripheral blood neutrophil responses to the chemoattractants leukotriene B4 (LTB(4)) and formyl-methionyl-leucyl-phenylalanin (fMLP) were investigated in vitro. Samples from 10 patients with PLE before and after 6 weeks of photohardening therapy were assessed. Flow cytometry was used to measure the changes associated with neutrophil activation. We found a significantly reduced neutrophil responsiveness to LTB(4) and fMLP in PLE patients, which was restored to normal levels after phototherapy. Indeed, PLE neutrophil responsiveness to these two chemoattractants after (but not before) phototherapy was similar to that of age- and sex-matched healthy control subjects. This indicates that an abnormal chemotactic potential to neutrophils is a crucial factor in the pathogenesis of PLE. Normalization following photohardening may therefore account for the therapeutic efficacy by restoring UV-induced neutrophil skin infiltration. Our results reveal a completely novel pathogenic mechanism involved in PLE and offer unique targets for therapy.     

Pyoderma gangrenosum in a child with congenital partial deficiency of leucocyte adherence glycoproteins

Congenital deficiency of β2 integrin leucocyte adhesion molecules is a rare immunodeficiency and is often fatal. Neutrophils are unable to bind to ligands on the endothelium, and so cannot leave the circulation during inflammation or infection. When leucocyte adhesion deficiency (LAD) is caused by abnormally low expression of β2 integrins, it is termed LAD type 1. We describe a 5-year-old girl with a history of recurrent bacterial infections since early childhood who developed necrotic skin ulcers resembling pyoderma gangrenosum and a persistent circulating neutrophilia. Histologically, the lesions showed deep ulceration with a diffuse lymphohistiocytic infiltrate, but with a relative sparsity of neutrophils. Subsequent investigation revealed a complete absence of CD11a/CD18 β2 integrins on the surface of the patient's neutrophils, confirming the diagnosis of LAD type 1. The ulcers responded to treatment with oral prednisolone and colchicine.     

Two cases of pyoderma gangrenosum complicated with nasal septal perforation

We report two patients with pyoderma gangrenosum complicated with nasal septal perforation. An 18-year-old woman and a 65-year-old man had typical lesions of pyoderma gangrenosum on the legs that responded well to oral prednisolone. Both patients complained of mild nasal discharge, and nasal fibroscopy revealed nasal septal perforation. Biopsy of the nasal lesions showed an active inflammatory infiltrate, mainly of neutrophils. Systemic investigations failed to show any pulmonary or renal lesions of Wegener's granulomatosis. Cytoplasmic immunofluorescent pattern antineutrophil cytoplasmic antibody was negative. In both cases, intense neutrophilic infiltration was observed not only in skin lesions but also in nasal lesions, which may indicate that the nasal lesions had a pathogenesis in common with the skin lesions.     

A case of acne fulminans in a patient with ulcerative colitis successfully treated with prednisolone and diaminodiphenylsulfone: a literature review of acne fulminans, rosacea fulminans and neutrophilic dermatoses occurring in the setting of inflammatory bowel disease

A 19-year-old Japanese man had been treated for ulcerative colitis for 2 years. He was admitted to our hospital with nodulocystic inflammatory papules and pustules on his face and chest, high-grade fever, arthralgia and general malaise. A biopsy specimen from a pustule showed prominent infiltration of neutrophils in the epidermis and dermis, particularly around hair follicles. We made a diagnosis of acne fulminans. The systemic administration of prednisolone at 30 mg daily for 1 week immediately improved his skin lesions and other symptoms; however, during tapering of prednisolone at 20 mg daily, skin lesions flared up. The addition of oral diaminodiphenylsulfone improved the skin lesions. Although there have been a few reports of acne fulminans associated with Crohn's disease, this is the first case report of acne fulminans in a patient with ulcerative colitis. It is noteworthy that the addition of diaminodiphenylsulfone was effective for treating the relapse of acne fulminans in this case.     

Kikuchi's disease and the skin: case report and review of the literature

We report scattered indurated erythematous lesions that presented in an 18-year-old Japanese man with Kikuchi's disease (KD; histiocytic necrotizing lymphadenitis). A skin biopsy showed a proliferation of histiocytes and abundant nuclear debris without the presence of neutrophils, which is characteristic of KD. The specific dermatological and pathological details of KD have been yet to be fully described. In order to assess the typical skin features of KD better, we have reviewed all the previously well-documented reports of such lesions. As the clinical and histopathological cutaneous findings in KD are so heterogeneous, it is important that scattered indurated erythematous lesions should be included as one of the possible cutaneous manifestations of this disease.     

Lupus pernio with multiple bone cysts in the fingers

A 32-year-old Japanese man presented with a 3-year history of purple reddish, and painful swelling of his fingers along with indurated erythema on his nose and ears. He was diagnosed as having sarcoidosis 8 years prior because of uveitis and bilateral hilar lymphadenopathy. X-rays of the hands revealed multiple cystic lesions in the phalanges. Histological examination of the ear revealed epithelioid cell granulomas in the dermis. Oral prednisolone 20 mg/day improved his finger swelling and pain; however, his finger deformities and erythema remain unchanged. Bone involvement is sometimes seen in sarcoidosis and the hands are the most frequently affected areas. The frequency of bone involvement is higher in lupus pernio in comparison with other types of skin sarcoidosis. Systemic corticosteroids could be the first choice of treatment to relieve the symptoms.     

Disseminated metastatic cutaneous Crohn's disease

Metastatic cutaneous Crohn's disease, in which non-caseating granulomatous infiltration of the skin occurs at sites separated from the gastrointestinal tract by normal tissue, is the least common dermatological manifestation of Crohn's disease. We report the case of an 18-year-old man who developed very widespread metastatic cutaneous Crohn's disease 2 years after he had first developed mild oral and anal lesions. His gastrointestinal symptoms had been satisfactorily controlled for 18 months with sulphasalazine alone prior to his developing skin lesions. The cutaneous lesions responded rapidly to oral prednisolone which was tailed off over 5 months and then withdrawn. He relapsed 6 months later and now requires a low dose of oral prednisolone to control the skin lesions. The only complication of this therapy has been exacerbation of mild acne vulgaris.     

Psoriatic keratinocytes prime neutrophils for an overproduction of superoxide anions

Psoriatic plaques result from an abnormal proliferation of keratinocytes associated with the local presence of T lymphocytes and neutrophils. The exact role of neutrophils in psoriatic lesions remains unclear. The present investigation was aimed at deciphering the capacity of psoriatic keratinocytes to alter in vitro functions of neutrophils. Blood neutrophils from healthy donors were incubated with psoriatic (PK) or healthy keratinocytes (HK) with and without IL-2-activated healthy T lymphocytes. The study was focussed on neutrophil capacity of adherence, viability and superoxide anion production. PK or HK with or without T lymphocytes similarly augmented neutrophil viability after 48 h of co-incubation. PK or HK did not directly activate the superoxide production by neutrophils. However, they both primed neutrophils for an increased fMLF-induced production of superoxide, an effect enhanced by the presence of T lymphocytes. PK were 1.5-fold more efficient than HK to augment this superoxide production. PK cultured with T lymphocytes induced the adhesion of neutrophils 4.7 times more efficiently than HK. The adherence of neutrophils was mediated through ICAM-1, LFA-1 and Mac-1, independently of bioactive lipids. The effects of PK and HK on neutrophil viability and priming were independent of direct cellular contact. In conclusion, keratinocytes can impact neutrophils by increasing their lifespan, and by priming them to overproduce superoxide. PK are more efficient than HK in priming neutrophils, an effect enhanced by T lymphocytes. These results indicate that neutrophils could contribute to psoriasis pathogenesis partly through their pathological interactions with PK.