Ryuichi Azuma

Accelerated wound healing in healing-impaired db/db mice by autologous adipose tissue-derived stromal cells combined with atelocollagen matrix.

Adipose tissue-derived stromal cells (ATSCs) have recently gained widespread attention as a potential alternate source to bone marrow–derived mesenchymal stem cells with a proliferative capacity and a similar ability to undergo multilineage differentiation. In this study, we evaluated the effectiveness of freshly isolated autologous ATSCs-containing atelocollagen matrix with silicon membrane (ACMS) on wound healing of diabetic (db/db) mice. Cultured ATSCs from (db/db) mice secreted significant amounts of growth factors and cytokines, which are suitable for wound repair. Two full thickness round skin defects were made on the backs of healing-impaired db/db mice. Freshly isolated autologous ATSCs-containing ACMS or ACMS alone were applied to the wounds. Twelve mice were treated and then killed at 1 or 2 weeks (n = 6 each). Histologic sections of the wounds were prepared at each time period after treatment. Histologic examination demonstrated significantly advanced granulation tissue formation, capillary formation, and epithelialization in diabetic healing-impaired wounds treated with autologous ATSCs-containing ACMS, compared with mice treated with ACMS alone. These results suggested that transplantation of autologous ATSCs-containing ACMS significantly accelerated wound healing in diabetic healing-impaired db/db mice.

Enhanced Effect of Platelet-Rich Plasma Containing a New Carrier on Hair Growth

BACKGROUND Treatments for alopecia are in high demand, but not all are safe and reliable. Dalteparin and protamine microparticles (D/P MPs) can effectively carry growth factors (GFs) in platelet‐rich plasma (PRP). OBJECTIVE To identify the effects of PRP‐containing D/P MPs (PRP&D/P MPs) on hair growth. METHODS & MATERIALS Participants were 26 volunteers with thin hair who received five local treatments of 3 mL of PRP&D/P MPs (13 participants) or PRP and saline (control, 13 participants) at 2‐ to 3‐week intervals and were evaluated for 12 weeks. Injected areas comprised frontal or parietal sites with lanugo‐like hair. Experimental and control areas were photographed. Consenting participants underwent biopsies for histologic examination. RESULTS D/P MPs bind to various GFs contained in PRP. Significant differences were seen in hair cross‐section but not in hair numbers in PRP and PRP&D/P MP injections. The addition of D/P MPs to PRP resulted in significant stimulation in hair cross‐section. Microscopic findings showed thickened epithelium, proliferation of collagen fibers and fibroblasts, and increased vessels around follicles. CONCLUSION PRP&D/P MPs and PRP facilitated hair growth but D/P MPs provided additional hair growth. The authors have indicated no significant interest with commercial supporters.

Paraneoplastic pemphigus mimicking erosive mucosal lichen planus associated with primary hepatocellular carcinoma

A 58‐year‐old Japanese male visited us with painful lesions on the lower lip, oral mucosa and genital region of an 8‐month duration. Histological features of the genital lesion were almost consistent with lichenoid tissue reaction. A few intraepidermal acantholytic keratinocytes were also seen in the suprabasal clefts. Direct immunofluorescence exhibited cell surface immunoglobulin (Ig)G deposition and linear deposition of fibrinogen at the dermoepidermal junction. IgG anti‐desmoglein (Dsg)3 antibody, but not anti‐Dsg1 antibody, was detected in the patients serum by enzyme‐linked immunosorbent assay. Immunoblotting using normal human epidermal extract detected the 210‐kD envoplakin, 190‐kD periplakin and 130‐kD Dsg3. The diagnosis of paraneoplastic pemphigus (PNP) was made. Subsequent investigation revealed a large space‐occupying lesion in the liver. Histological findings from liver biopsy specimen were consistent with hepatocellular carcinoma. The patient has been alive 38 months after the diagnosis of PNP was made, although the liver mass has slowly enlarged. Our case is clinically and histologically similar to erosive mucosal lichen planus. Immunological studies confirmed the diagnosis of PNP. The results of negative Dsg1 and positive Dsg3 were consistent with clinical features showing severe mucosal involvement without cutaneous erosion. In PNP, the association with non‐hematological solid tumor is extremely rare.

Urticarial vasculitis presenting as erythema gyratum repens‐like eruption

© 2008 The Authors JEADV 2009, 23, 169–243 Journal compilation

Recalcitrant pemphigus foliaceus with Kaposi’s varicelliform eruption: report of a fatal case

An 88-year-old man presented with a 10-day history of erosive skin lesions on the trunk. On physical examination, multiple erythematous areas and erosions with flaccid bullae were found on the trunk and upper limbs. The oral mucosa was not involved. History of recurrent herpes simplex labialis or genitalis was uncertain. Histology showed subcorneal blisters with acantholytic keratinocytes in the upper epidermis. Direct immunofluorescence revealed IgG and C3 on the intercellular spaces of the epidermis. IgG antidesmoglein (Dsg)1 antibody was 960 (cut-off value 1⁄4 14), but antiDsg3 antibody was not detected in the patient s serum by ELISA (cut-off value 1⁄4 7). A diagnosis of pemphigus foliaceus (PF) was made, and the patient admitted to hospital. A regimen of oral prednisolone 40 mg daily was begun, but this did not control the skin lesions. Prednisolone was increased to a 100 mg and combined with azathioprine 100 mg daily. On the day after hospital admission, denuded areas which caused a severe burning sensation, appeared on the buttocks and trunk. The patient was febrile (37.8 C). Cutaneous examination revealed umbilicated vesicles and bullae widely disseminated and coalesced into large ulcers over the entire trunk (Fig. 1). Additionally, numerous, discrete, crusted ulcerative lesions appeared on the face (Fig. 2). Laboratory tests revealed raised liver enzymes including serum aspartate aminotransferase 1138 mU ⁄ mL (normal 5–43) and alanine aminotransferase 890 mU ⁄ mL (5–60), suggesting possible herpes hepatitis. IgG anti-Dsg1 ELISA index was increased to 1640, although anti-Dsg3 antibody was not detectable. Serum herpes simplex virus (HSV) antibodies IgG and IgM were measured by ELISA as > 128 (index) and 13.9 (positive), respectively. This suggested reactivation of HSV rather than an initial infection. Kaposi s varicelliform eruption was diagnosed and intravenous aciclovir was administered. Methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa were also PD

Localized pemphigoid (pretibial type) with IgG antibody to BP180 NC16a domain successfully treated with minocycline and topical corticosteroid.

sclerotic skin lesions along Blaschko’s lines, usually involving a single unilateral change in the frontoparietal area of the head. We report the case of a Japanese woman with this disease, which initially developed as a plaque-type morphealike lesion on the vertex and gradually spread into the frontoparietal region along a Blaschko’s line. A 22-year-old Japanese woman visited our hospital because of a circumscribed round area of hair loss on the scalp. She had found a small area of hair loss on the vertex region 2 years previously. Since then, the hair loss region had gradually enlarged, without specific symptoms. At presentation, she had an asymptomatic, well-circumscribed, round area of nonscarring hair loss, about the size of a hen’s egg, on the vertex region (Fig. 1a). The plaque was slightly depressed and had a few normal hairs. The adjacent skin was normal. There were no other similar skin lesions on the rest of the body. She did not report previous clinical signs of arthralgia, myalgia, or unexplained fever. There was no family history of collagen diseases. Routine blood test and urinalysis were normal. Autoantibody testing showed positive antinuclear antibody (1 : 320, speckled pattern) and negative rheumatoid factor and antisingle-stranded DNA antibody. A skin biopsy taken from the peripheral region of the plaque showed atrophy of epidermal appendages, thickened and hyalinized collagen bundles, and a mild perivascular lymphocytic infiltration in the dermis. She was given a diagnosis of plaque-type morphea, and treated with topical corticosteroids. However, no significant effect had been observed. During the follow-up period of 5 years, a slightly depressed linear lesion gradually developed from the left front edge of the plaque to the left frontoparietal region (Fig. 1b). As this lesion spread along a Blaschko’s line, we diagnosed this case as linear scleroderma en coup de sabre . An electroencephalogram and a cerebral computerized tomography scan revealed no abnormalities. Throughout the whole course of the follow-up period, no additional skin lesion had developed on the rest of the body and there had been no change in the blood results. In 2001, Happle et al. demonstrated the distribution of Blaschko’s lines on the head and neck. According to their report, the lines show a spiral configuration that culminates on the vertex. Based on these previous data, we speculated that the plaque-type morphea-like lesion was formed as a result of spiral distribution of a linear sclerotic lesion on the vertex. Although we cannot deny the coexistence of a plaque-type morphea with linear scleroderma, it is reasonable to explain the present case as an unusual case of linear scleroderma en coup de sabre , which affects the vertex region as well as the frontoparietal region. Our case suggests that a plaque-type morphea-like lesion on the vertex should be carefully followed up because it may be an unusual clinical manifestation of linear scleroderma en coup de sabre spreading along Blaschko’s lines. Y. Asano, H. Ihn* and K. Tamaki Department of Dermatology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan; and *Department of Dermatology and Plastic and Reconstructive Surgery, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan E-mail: yasano-tky@umin.ac.jp Conflict of interest: none declared. Accepted for publication 9 April 2007

A case of nodular cystic fat necrosis with systemic lupus erythematosus presenting the multiple subcutaneous nodules on the extremities

Editor Nodular cystic fat necrosis (NCFN) is a rare dermatosis characterized by the subcutaneous nodules with the histologic features of encapsulated fat necrosis showing membranocystic lesion. We describe a case of NCFN with systemic lupus erythematosus (SLE) presenting numerous subcutaneous nodules on the forearms and lower legs. A 62-year-old Japanese woman presented with a 1-year history of multiple subcutaneous nodules on the extremities. She had noted an asymptomatic nodule of the left forearm for 5 years. The nodules had increased in number and spread to the extremities for the last 1 year. She had suffered from anaemia, joint pain, and Raynaud’s phenomenon with the positivity of antinuclear antibody. She was diagnosed with SLE and had been treated with dexamethasone discontinuously for 15 years. On physical examination, the mobile, firm, subcutaneous nodules were symmetrically distributed on the bilateral forearms and lower legs. These nodules measured 1 to 5 mm in diameter, and the number of the nodules was more than 40 (fig. 1). The skin of her forearms and legs revealed atrophic changes probably due to the long-term corticosteroid therapy for SLE. Erythrocyanosis was also seen on the hands and feet, which resembled chilblain. Two subcutaneous nodules taken from the right forearm revealed the similar histologic features: well-demarcated, round-shaped nodules that consisted of matured adipose cells encapsulated by the fibrous tissue. Centre and peripheral portions of the nodules disclosed lipomembranous changes (fig. 2). Sixteen months after the first visit, the subcutaneous nodules showed decreased in size and number. NCFN is the diagnostic term advocated by Przyjemski and Schuster in 1977. Hurt et al. suggested that mobile encapsulated lipoma and encapsulated fat necrotic nodules should be integrated into NCFN. In general, NCFN occurs predominantly on the lower legs in female. The number of the nodules is usually less than 10. The most impressive part of her clinical features was the numerous nodules symmetrically distributed on the forearms and lower legs, which differed distinctively from previously reported NCFN. The aetiology of NCFN is unknown. There are several hypotheses with regard to pathogenesis: (i) trauma, (ii) ischemia by rapid vascular insufficiency, (iii) panniculitis or fat necrosis due to the corticosteroid therapy. The patient had SLE and received the long-term systemic corticosteroid therapy. She had skin atrophy caused by steroid administration and erythrocyanotic lesion of hands and feet resembling chilblain due to vascular insufficiency. Accordingly, the vascular insufficiency of the extremities related to SLE and fat degeneration by the long-term corticosteroid therapy may be involved in the pathomechanisms of NCFN in the present case. Although lipomembranous changes can be seen in lupus panniculitis, the association of NCFN with SLE has not been reported. Toritsugi et al. described a case of mobile subcutaneous nodules and histologically by encapsulated fat necrosis associated with systemic sclerosis. This is the first reported case of NCFN with SLE presenting multiple subcutaneous nodules on the extremities. The peripheral circulation disturbance due to SLE and the fat damages caused by the long-term corticosteroid administration may be responsible for the development of multiple NCFN in the present case. We think that many similar cases may be under-reported. NCFN should be listed up in a differential diagnosis when dermatologists encounter fig. 1 Multiple subcutaneous nodules on the forearm. fig. 2 An encapsulated tumour contains mature adipose cells showing lipomembranous fat necrosis in the centre of the lesion.

Two cases of cutaneous phaeohyphomycosis due to Exophiala jeanselmei: diagnostic significance of direct microscopical examination of the purulent discharge.

Phaeohyphomycosis (PHM) is a fungal skin infection, usually caused by Exophiala jeanselmei. The disease is characterized by a cutaneous or subcutaneous nodule, which predominantly occurs on the exposed areas of the skin surface, particularly the limbs. PHM is known to arise at the site of trauma and often occurs in immunocompromised hosts such as those under treatment with systemic corticosteroid, recipients of organ transplantation or people with haematological malignancies. Generally, the diagnosis of PHM is confirmed by histological examination, which reveals the morphology of fungal elements in the tissue, and by mycological findings. There have been few reports about direct microscopical examination of the purulent discharge for the early diagnosis of PHM, although the usefulness of the direct potassium hydroxide (KOH) test for detecting sclerotic cells in chromomycosis is well known. We report two cases of PHM due to E. jeanselmei in immunocompromised patients and emphasize the usefulness for the diagnosis of PHM of direct microscopical examination of discharge from skin lesions. Patient 1 was a 75-year-old Japanese man, who was referred to our department with a subcutaneous abscess on the left lower leg. He had first noticed the lesion 1 week previously, but was uncertain about the precise onset of the skin lesion because it was asymptomatic. The patient had

Urticarial vasculitis with haemorrhagic vesicles successfully treated with reserpine.

1006

Neutrophilic, urticaria-like erythema associated with immunoglobulin A monoclonal gammopathy of undetermined significance

A 70‐year‐old‐male had suffered from non‐pruritic, erythematous eruptions on the trunk for 3 months without any general symptoms. The individual lesions lasted for several days. Laboratory investigation showed marked elevation of serum immunoglobulin A (2235 mg/dL) with monoclonal gammopathy (IgA k‐type). Monoclonal gammopathy of undetermined significance was diagnosed. Histopathological examination of the eruption revealed diffuse neutrophilic infiltration with leukocytoclasia in the dermis. There was no vasculitis. Treatment with antihistamines alone was not effective. Diaphenyl sulfone (DDS) at 75 mg/day dramatically improved the skin lesions. A similar case of urticarial erythema associated with IgA myeloma has been previously reported. We suggest that neutrophilic, urticaria‐like erythema associated with IgA monoclonal gammopathy may be regarded as a new entity.