Noriko Yoshii

Efficacy of topical tacrolimus for treating the malar rash of systemic lupus erythematosus

Summary The rash of systemic lupus erythematosus (SLE) is usually treated with topical corticosteroids, but prolonged use causes adverse cutaneous side‐effects. We assessed the efficacy of topical tacrolimus for treating the skin lesions of SLE. Three patients with SLE affecting their facial skin applied 0·1% tacrolimus ointment on one side of their face twice daily for 3 weeks, in conjunction with a sunscreen cream. After 3 weeks, erythema on the treated side was ameliorated in all three patients compared with the untreated side. Although the study is preliminary, the results demonstrate that topical tacrolimus may be useful for treating the malar rash of SLE.

Expression of mucin core proteins in extramammary Paget's disease

Extramammary Pagets disease (EPD) is a relatively common skin cancer wherein tumor cells have mucin in their cytoplasm. However, little is known about mucin expression in EPD. We examined immunohistochemically the expression of mucin core proteins (MUC1, MUC2, MUC5AC and MUC6) in 36 cases of EPD and found different patterns of expression in intraepithelial (n = 36), microinvasive (n = 13) and invasive lesions (n = 6). In normal skin, MUC1 was expressed in the sebaceous, eccrine and apocrine glands. MUC2, MUC5AC and MUC6 were not expressed in any of these. In the 36 intraepithelial lesions, MUC1 and MUC5AC were expressed in 35 and 36 lesions, respectively. MUC1 expression was also observed in all 13 microinvasive lesions and in all six invasive lesions. In contrast to the intraepithelial lesions, a decrease or loss of MUC5AC expression was observed in five out of 13 microinvasive lesions and in all six invasive lesions. MUC2 and MUC6 were not expressed in any of the EPD lesions examined. The combination of immunohistochemical staining for MUC1 and MUC5AC was useful for identifying invasive Paget cells. The decrease or loss of MUC5AC expression may have an important role in the invasive growth of Paget cells.

Treatment of pustular psoriasis with granulocyte and monocyte adsorption apheresis

We studied the efficacy of granulocyte and monocyte adsorption apheresis in 2 patients with pustular psoriasis, one localized, the other generalized. Treatment with granulocyte and monocyte adsorption apheresis resulted in remarkable clearing of the skin lesions, suggesting that this therapy is a valuable tool for treating patients with intractable skin diseases attributable to activated granulocytes. We present detailed descriptions of these patients and this novel therapy.

A new case of alpha-N-acetylgalactosaminidase deficiency with angiokeratoma corporis diffusum, with Meniere's syndrome and without mental retardation

α‐N‐acetylgalactosaminidase (α‐NAGA) deficiency is a rare hereditary lysosomal storage disease, and only three α‐NAGA‐deficient patients with angiokeratoma corporis diffusum (Kanzaki) have been described. We report a further case in a 47‐year‐old Japanese woman, the product of a consanguineous marriage. The remarkable findings in this patient were her normal intelligence, Ménières syndrome, disturbance of peripheral sensory nerves, hearing loss and cardiac hypertrophy. α‐NAGA enzyme activity in her plasma was 0·77% of the normal value. Other enzyme activities, such as α‐galactosidase, β‐galactosidase, α‐l‐fucosidase, β‐mannosidase and aspartylglucosaminidase, were within normal limits. A large quantity of amino acid O‐glycans was detected in her urine. Gene analysis revealed a novel point mutation (G→A transition) at nucleotide 11018 (986 in the cDNA) resulting in an Arg‐329‐Gln substitution. Kanzaki disease has the same enzyme defect as Schindler disease, but the manifestations are quite different.

Syringoma-like eccrine sweat duct proliferation induced by radiation.

We report a 45‐year‐old woman with breast cancer who had undergone surgery and radiation and anti‐estrogen therapy and presented with many reddish papules in the irradiated breast area. Skin biopsy of the affected area disclosed proliferation of eccrine sweat ducts and cystic structures; the clinical and histopathological features were consistent with syringoma‐like eccrine sweat duct proliferation. The lesions spread rapidly on her chest during radiation therapy and regressed spontaneously 3 weeks after its completion. We postulate that the lesions were induced by radiation, and promoted by anti‐estrogen therapy.

Immunohistochemical comparison of β-catenin expression by human normal epidermis and epidermal tumors

β‐Catenin, a cytoplasmic protein that binds directly to the intracellular domain of cadherin, controls various functions such as cell adhesion. In many human carcinomas, E‐cadherin‐mediated cell–cell adhesion is lost or disturbed and related to metastasis. The purpose of this study was to compare the expression of β‐catenin in the normal epidermal keratinocytes and samples from cutaneous benign and malignant epidermal tumors in 140 patients. Our study population consisted of 140 patients with benign or malignant epidermal tumors. Using immunohistochemical methods, we compared the expression of β‐catenin in their normal epidermal keratinocytes, and in samples from 61 benign (seborrheic keratosis, n = 33; verruca vulgaris, n = 14; keratoacanthoma, n = 14), and 79 malignant (Bowens disease, n = 18; basal cell carcinoma, n = 33; squamous cell carcinoma, n = 28) epidermal tumors. β‐Catenin was found to be expressed in the cell membrane of normal keratinocytes. Compared to other cell components of the normal epidermis, basal cells showed the strongest β‐catenin expression in all 140 patients. While absent in three of 61 benign tumors, compared to normal basal cells, the expression of β‐catenin in the other 58 tumors was not significantly different; it was reduced in 71 of 79 malignant tumors (P < 0.0001). In Bowens disease, the expression of β‐catenin on the tumor cell membrane was reduced, however, strong expression was seen in the nuclei and cytoplasm. Our results suggest that β‐catenin expression on the membrane of keratinocytes is associated with the differentiation of normal keratinocytes but not with their stage of differentiation, nor with the proliferation ability of epidermal tumor cells.

Facial paraffinoma after cosmetic paraffin injection.

Dear Editor, Paraffinoma is characterized by a granulomatous inflammation of the skin due to exogenous paraffin. We encountered a 74-year-old Japanese woman with paraffinoma of the face that developed 40 years after cosmetic paraffin injections. She noticed indurated erythematous lesions with local heat sensation on her bilateral cheeks 2 months prior to visiting our department. Examination of the lesions that had expanded to affect her forehead revealed indurated erythematous plaques on her forehead and bilateral cheeks (Fig. 1). Cheek and forehead biopsy showed dense inflammatory infiltrates involving the entire dermis and epithelioid granulomas without caseation necrosis. Round or ovoid clear vacuoles, varying in size up to approximately 50 μm, were scattered in the dermis (Fig. 2). The results of routine laboratory examinations and her serum angiotensin-converting enzyme level were within normal limits. Acid-fast bacteria staining demonstrated no microbes. Chest X-ray and ophthalmological examinations revealed no abnormal findings. Repeat biopsy for fat stains and electron microscopic (EM) studies showed positive vacuolar fat staining with oil red O and Sudan IV (Fig. 3). There were minute clear deposits in the cytoplasm of macrophages (Fig. 4) that were not stained by osmium acid. Consequently, a diagnosis of paraffinoma was made and she received systemic prednisolone, 20 mg daily. Her skin lesions subsided gradually. Paraffinoma, defined as a granulomatous foreign body reaction, results from the i.d. injection of oily substances containing long-chain acyclic hydrocarbons. It usually manifest as irregular plaque-like indurations of the skin. Macroscopically, excised specimens are white or grayish-white; microscopically, there is granulomatous inflammation with multiple clear vacuoles, resulting in the so-called “Swiss cheese” appearance which was not clearly evident in our case. Because our patient received paraffin injections in the 1960s, we could exclude silicone granuloma. Paraffinoma is characterized by dense inflammatory infiltrates and fewer multinucleated giant cells than are seen in silicone granulomas. In our biopsy specimen, inflammatory infiltrates were dense throughout the dermis and giant cells were absent. In frozen sections, vacuoles were positive for fat stains with Sudan IV and oil red O; on EM study, they were negative for osmic acid.

Improvement of adult Still's disease with granulocyte and monocyte adsorption apheresis.

Adult Stills disease is characterized by a high spiking fever, transient skin rash, and polyarthralgia. Joint pain is one of the major complaints and is often intractable. We assessed the efficacy of granulocyte and monocyte adsorption apheresis (GCAP) therapy for treating arthralgia in adult Stills disease. A 33‐year‐old woman with adult Stills disease who suffered from recalcitrant arthralgia resistant to systemic corticosteroids was treated with GCAP therapy. She underwent five GCAP treatments at 5‐day intervals. Her joint pain responded dramatically to the GCAP therapy, suggesting that GCAP may be useful for treating adult Stills disease. We present a detailed description of the patient and this novel therapy.

Erythema elevatum diutinum manifesting as a penile ulcer.

Erythema elevatum diutinum (EED) is a rare cutaneous condition characterized by persistent red or purple papulonodular plaques and prominent neutrophilic infiltration. We recently encountered a patient with EED affecting the penis. This 74-year-old man manifested red or violaceous nodules, 10–20 mm in size, 1 on his knees, lower legs, and feet (Fig. 1a). A biopsy specimen from his knee revealed acanthosis and dense infiltration by neutrophils in the vicinity of the vessels throughout the dermis (Fig. 2a). Nuclear dust, eosinophils and extravasated red blood cells were seen in the dermis (Fig. 2b). His white blood cell count was 10.6 · 10 ⁄ L; other laboratory results were unremarkable. We made a diagnosis of EED, although chest X-ray, abdominal ultrasonography, colon fiberscopy, echocardiography, and haematological examinations showed none of the other systemic disorders often associated with EED. Because we had found nicotine to be useful for intractable skin diseases attributable to activated neutrophils, we Figure 1 Lesions (arrowed) visible on (a) the front and (b) the back of the thighs 3 .

Eruptive pruritic papular porokeratosis: A pruritic variant of porokeratosis

Porokeratosis is a chronic skin disorder characterized clinically by the presence of crater‐like patches with an elevated thick keratotic border and central atrophy. Histology reveals cornoid lamellae. While porokeratosis is practically asymptomatic, a pruritic variant has been reported. We recently encountered an 82‐year‐old man with pruritic porokeratosis. He presented with erythematous papules and intensively itchy patches on his lower limbs that had been present for 6 months. Histopathological examination revealed the characteristic cornoid lamellae. We describe this case in detail and provide a review of the published work.