Masanao Sakanoue

Granulocyte and monocyte adsorption apheresis for refractory skin diseases due to activated neutrophils, psoriasis, and associated arthropathy.

Granulocyte and monocyte adsorption apheresis (GMA), an extracorporeal apheresis instrument whose column contains cellulose acetate (CA) beads, is designed to remove activated granulocytes and monocytes. We previously demonstrated that GMA was useful for treating neutrophilic dermatoses and associated arthropathy as it adsorbs Mac‐1 (CD11b/CD18)‐expressing neutrophils to the CA beads by the binding of complement component (iC3b) and CD11b expressed on activated neutrophils. The objective of this study is to further assess the clinical effectiveness of GMA in the treatment of neutrophilic dermatoses and associated arthropathy. The effect of GMA for skin lesions and joint lesions was assessed in 44 and 23 patients, respectively. Mac‐1 expression on peripheral neutrophils was measured by flow cytometry. Skin lesions and arthropathy improved in 39 of 44 patients (88.6%) and 22 of 23 (95.6%), respectively. Mac‐1 (CD11b/CD18) expression on the peripheral neutrophils, 27.1 ± 6.66 MFI (mean fluorescence intensity) before treatment, was reduced to 17.9 ± 3.02 MFI by GMA (P < 0.05). Clinical effectiveness of GMA for the treatment of intractable neutrophilic dermatoses and associated arthropathy was further confirmed.

A case of anaphylaxis caused by polyethylene glycol analogues

A case of anaphylaxis caused by polyethylene glycol analogues Yoshiko Yamasuji1, Yuko Higashi1, Masanao Sakanoue1, Hiromi Katsue1, Kazuhiro Kawai1, Noriyoshi Arai2 and Takuro Kanekura1 1Department of Dermatology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, 890-8520, Japan and 2 Division of Chemical Process Engineering, Hokkaido University, Sapporo, 060-8628, Japan

Granulocyte and monocyte adsorption apheresis as an effective treatment for Reiter disease

Reiter disease (RD) is characterized by a triad of sterile arthritis, urethritis and conjunctivitis. The conditions occur concomitantly or sequentially, and are associated with mucocutaneous features such as circinate balanitis and stomatitis. Arthritis usually occurs in attacks followed by recovery, but it sometimes progresses to permanent damage of the affected joints. Because the symptoms of this disorder are attributable to activated neutrophils, we assessed the efficacy of granulocyte and monocyte adsorption apheresis (GCAP) in a 73‐year‐old man with RD who had skin rashes on his penis, scrotum and right hand, with severe arthralgia. The patient’s skin rash and joint pain responded dramatically to five sessions of GCAP delivered at intervals of 5 days. We present a detailed description of the patient and discuss the mechanisms of GCAP, and suggest that GCAP may be useful for treating RD.

Granulocyte and monocyte adsorption apheresis for palmoplantar pustulosis with extra-palmoplantar lesions and pustulotic arthro-osteitis

Dear Editor, Palmoplantar pustulosis (PPP) is a chronic inflammatory disorder characterized by sterile pustules on the palms and soles. In rare cases, extra-palmoplantar lesions and arthro-osteitis are seen. It is treated with topical or systemic anti-inflammatory and other drugs and ultraviolet therapy. Tumor necrosis factor-a (TNF-a) is involved in its pathogenesis. We reported the effectiveness of granulocyte and monocyte adsorption apheresis (GMA) for intractable skin diseases in whose development myeloid lineage cell-derived TNF-a plays a pivotal role. Here, we present a patient with PPP with extra-palmoplantar lesions and pustulotic arthro-osteitis treated successfully with GMA. A 47-year-old man with a 6-month history of pustules on his soles was given a diagnosis of PPP elsewhere. Treatment with oral minocycline, 200 mg daily for 14 days, and topical corticosteroid, betamethasone butyrate, was not effective and sharp pain developed on his chest and shoulders around the scapulae. Physical examination at our department revealed pustules on his arm (Fig. 1a) and soles (Fig. 1b) and acneiform

Inhibition of Inflammatory Cytokines and Induction of Myeloid‐Derived Suppressor Cells by the Effects of Granulocyte and Monocyte Adsorption Apheresis

Pro‐inflammatory cytokines are involved in the pathogenesis of inflammatory skin diseases attributable to activated neutrophils and macrophages. Myeloid‐derived suppressor cells (MDSCs) play an important role in the regulation of the immune response and possess strong immunosuppressive and anti‐inflammatory properties. Granulocyte and monocyte adsorption apheresis (GMA), an extracorporeal apheresis instrument featuring columns containing cellulose acetate (CA) beads, is designed to remove pathogenic myeloid lineage cells. The purpose of this study was to investigate the effects of GMA on cytokine production and MDSC induction. The serum level of various inflammatory cytokines and the incidence of MDSCs in peripheral blood before and after GMA treatment were recorded. Cytokines were assayed with the suspension‐array method in 38 patients. The incidence of MDSCs was analyzed by FACS in eight patients and the effect of GMA on in vitro MDSC induction was examined using a mini‐column system that mimics GMA. The serum level of IL‐2Rα (P = 0.030), IL‐8 (P = 0.018), and MIF (P = 0.0002) was significantly decreased by GMA and the incidence of MDSCs was increased (P = 0.030). With the mini‐column system, MDSCs were induced in the peripheral blood of five healthy volunteers; the in vitro induction was significantly inhibited by inactivation of the complement component iC3b. The clinical effectiveness of GMA may be attributable to the inhibition of pro‐inflammatory cytokines and the induction of anti‐inflammatory MDSCs by iC3b activation via the CA beads in the GMA column.

Bullous pemphigoid associated with type 1 diabetes mellitus responsive to mycophenolate mofetil.

1 Egan CA, Lazarova Z, Darling TN, Yee C, Yancey KB. Anti-epiligrin cicatricial pemphigoid: clinical findings, immunopathogenesis, and significant associations. Medicine (Baltimore) 2003; 82: 177–186. 2 Dainichi T, Takeshita H, Moroi Y et al. Cicatricial pemphigoid with autoantibodies against the laminin 5 gamma 2 subunit. Eur J Dermatol 2005; 15: 189–193. 3 Hsu R, Lazarova Z, Yee C et al. Noncomplement fixing, IgG4 autoantibodies predominate in patients with anti-epiligrin cicatricial pemphigoid. J Invest Dermatol 1997; 109: 557–561. 4 Egan CA, Lazarova Z, Darling TN, Yee C, Coté T, Yancey KB. Anti-epiligrin cicatricial pemphigoid and relative risk for cancer. Lancet 2001; 357: 1850–1851. 5 Taniuchi K, Takata M, Matsui C et al. Antiepiligrin (laminin 5) cicatricial pemphigoid associated with an underlying gastric carcinoma producing laminin 5. Br J Dermatol 1999; 140: 696–700.

Henoch–Schönlein purpura with epididymitis in an adult

1 Shitara A. Lupus miliaris disseminatus faciei. Int J Dermatol 1984; 23: 542–544. 2 Shitara A. Clinicopathological and immunological studies of lupus miliaris disseminatus faciei. J Dermatol 1982; 9: 383–395. 3 Berbis P, Privat Y. Lupus miliaris disseminatus faciei: efficacy of isotretinoin. J Am Acad Dermatol 1987; 16: 1271–1272. 4 Veien NK, Stahl D, Brodthagen H. Granulomatous rosacea treated with tetracycline. Dermatologica 1981; 163: 267–269. 5 Brinkmeier T, Schaller J, Herbst RA, Frosch PJ. Successful treatment of acquired reactive perforating collagenosis with doxycycline. Acta Derm Venereol 2002; 82: 393–395.

Skin eruption elicited by magnesium oxide (Maglax(

Magnetic resonance imaging (MRI) showed the tumor to be localized at the cutaneous site, with no sign of invasion toward the urostomy (Fig. 1d). We excised the tumor with a 5-mm margin. At the mucosal site, the urologist surgeon made a local monopolar excision to the depth of the chorionic membrane (Fig. 1e). We designed a hatchet flap on the lateral side of the skin defect part and performed reconstruction by rotating the flap (Fig. 1f,g). Surgical specimens showed regular papillary acanthosis consisting of keratinocytes. The upper dermis showed a moderate amount of inflammatory infiltrates. Atypical nuclei were partially seen, and the bottom line of the tumor was generally clear (Fig. 1h–l). We performed polymerase chain reaction (PCR) analysis to detect human papilloma virus (HPV), including 16 subtypes of HPV (6, 11, 16, 18, 30, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 66). However, none of these types were identified. Although we also considered VH as a differential diagnosis, VH is the name of a disease occurring on a mucosal site. Based on these clinical and histopathological findings, we made the final diagnosis of CPD. In this case, we first speculated from the biopsy specimen that the tumor was a verrucous tumor, including malignancy. Based on MRI imaging, we were able to choose surgical treatment without relocation of the stoma. Therefore, the patient was able to be discharged and return to productive life within several days, and the final diagnosis of CPD was made according to histopathological findings and the result of PCR analysis of HPV. In conclusion, we described a rare case of CPD arising on the stomal site. The collaboration between urologists and skin surgeons become contributory in diagnosing and treating tumors around stomal sites. It is clear that we skin surgeons play an important role. When we deal with tumors around stoma, we should keep CPD in mind as a differential diagnosis.

Allergic reaction caused by acesulfame potassium in foods.

The increasing frequency of obesity and related diseases such as diabetes and hypertension is an important healthcare issue. The use of artificial sweeteners has increased in recent decades, for the purpose of limiting excessive calorie intake (1). A large variety of nonnutritive sweeteners are available. Acesulfame potassium is one of these artificial sweeteners, and is used in many types of food and drink. Allergic reactions to artificial sweeteners are very rare. Only a limited number of cases of urticaria and anaphylaxis induced by aspartame (2, 3) and erythritol (4, 5) have been reported previously. We report a patient with allergic reactions caused by acesulfame potassium.

Striate palmoplantar keratoderma.

Figure 1. (a) Linear hyperkeratosis on the flexor aspects of both thumbs and index fingers. There were focal areas of hyperkeratosis on the palms. (b) Focal hyperkeratosis on the weight-bearing areas of both feet including the plantar aspects of the heel, forefoot and big toe. (c) Marked orthohyperkeratosis, acanthosis and hypergranulosis. There was no evidence of epidermolytic hyperkeratosis (hematoxylin– eosin, bar = 300 lm). (d) Widening of intercellular spaces and abnormal cytoplasmic condensation in some keratinocytes in the spinous layers of the epidermis (hematoxylin– eosin, bar = 30 lm). Dear Editor, Striate palmoplantar keratoderma (SPPK) of Brünauer–Fuhs–Siemens is a rare autosomal dominant genodermatosis characterized by linear hyperkeratosis on the digits and palms and focal hyperkeratosis on the soles. SPPK is known to be caused by heterozygous mutations in either the desmoglein 1 (DSG1) (type I SPPK, Online Mendelian Inheritance in Man [OMIM] no. 148700), desmoplakin (DSP) (type II SPPK, OMIM no. 612908), or keratin 1 (KRT1) (type III SPPK, OMIM no. 607654) gene. Only five cases of SPPK, including two unrelated familial cases and three sporadic cases, have been reported in Japan. The mutated gene(s) in these five Japanese cases have not been identified, although one patient was associated with Rubinstein–Taybi syndrome. We report the sixth Japanese case of SPPK. Although we were unable to perform genetic studies, we speculate that our case might be type I SPPK caused by a mutation in the DSG1 gene because the ultrastructural features were similar to a previously reported case. A 38-year-old Japanese man presented with a 25-year history of severe plantar calluses and a 13-year history of linear hyperkeratosis on the palmar aspects of both thumbs and index fingers (Fig. 1a,b). There were no hair, nail or dental abnormalities and no evidence of cardiac diseases. He stated that his father also suffered from plantar calluses and that no other family members including his 9-year-old son were affected. A biopsy specimen obtained from the lateral heel skin exhibited marked hyperkeratosis, acanthosis and hypergranulosis without granular degeneration (Fig. 1c). At higher magnification, widening of the intercellular spaces was evident in the spinous layers of the epidermis (Fig. 1d). Based on these clinical and histological features, a diagnosis of SPPK was made. He was treated with topical maxacalcitol ointment, but he was lost to follow up 2 months after the initiation of therapy.