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Primary cutaneous amyloidosis (PCA) is an itchy skin disorder associated with amyloid deposits in the superficial dermis. The disease is relatively common in Southeast Asia and South America. Autosomal dominant PCA has been mapped earlier to 5p13.1-q11.2 and two pathogenic missense mutations in the OSMR gene, which encodes the interleukin-6 family cytokine receptor oncostatin M receptor beta (OSMRbeta), were reported. Here, we investigated 29 Taiwanese pedigrees with PCA and found that 10 had heterozygous missense mutations in OSMR: p.D647V (one family), p.P694L (six families), and p.K697T (three families). The mutation p.P694L was associated with the same haplotype in five of six families and also detected in two sporadic cases of PCA. Of the other 19 pedigrees that lacked OSMR pathology, 8 mapped to the same locus on chromosome 5, which also contains the genes for 3 other interleukin-6 family cytokine receptors, including interleukin-31 receptor A (IL31RA), which can form a heterodimeric receptor with OSMRbeta through interleukin-31 signaling. In one family, we identified a point mutation in the IL31RA gene, c.1562CT that results in a missense mutation, p.S521F, which is also sited within a fibronectin type III-like repeat domain as observed in the OSMR mutations. PCA is a genetically heterogeneous disorder but our study shows that it can be caused by mutations in two biologically associated cytokine receptor genes located on chromosome 5. The identification of OSMR and IL31RA gene pathology provides an explanation of the high prevalence of PCA in Taiwan as well as new insight into disease pathophysiology.

The clinical findings of systemic amyloidosis are often variable and nonspecific. The early recognition of this disorder relies upon clinical suspicion, and definite diagnosis requires the confirmation of amyloid deposits in tissue. We reviewed 31 skin biopsy specimens from 20 patients, including 17 with amyloid light chain (AL) protein amyloidosis and 3 with serum amyloid A (AA) protein amyloidosis. Histologically, amyloid can be present in the papillary dermis, reticular dermis, subcutis, around the appendages, and in or around blood vessels. In our series, all 20 patients had at least one positive skin biopsy. Amyloid was found in 30 of 31 specimens (97%), a higher rate than in most series. Skin biopsy is a simple, safe procedure with high yield and may be used to obtain a firm diagnosis of systemic amyloidosis.

We report a case of Wells' syndrome (eosinophilic cellulitis) with acute cutaneous swelling followed by indolent infiltration. The histopathology is characterized by a dense infiltrate of eosinophils and "flame figures" in the dermis. The electron microscopic findings are peculiar. This case responded well to oral antihistamines. The skin signs and symptoms disappeared completely two weeks later.

We report a case of systemic amyloidosis with the initial sign of polyneuropathy. The patient eventually developed heart failure, macroglossia, and ecchymoses 6 years later. Biopsies from the sural nerve and normal-looking skin both proved the existence of amyloid.

We reviewed 86 cases of bullous pemphigoid and the results were compared with those reported in the literature. Seventy-eight per cent of the patients developed generalized blisters and 22% had localized blisters, including three cases of dyshidrosiform pemphigoid and one case of pretibial pemphigoid. Oral mucosal involvement was noticed in 12.8% of the patients. Fifteen per cent of the patients had internal malignancies but the incidence was not significantly different from the control group. Direct immunofluorescence in our series showed a high positive rate of 98.8%. Indirect immunofluorescence was positive in 48.1% of the 54 patients in whom this was carried out. Peripheral blood eosinophilia was observed in 22.1% of the patients. Prednisolone alone or in combination with immunosuppressive agents was the mainstay of treatment. Treatment side-effects was observed in 33% of the patients. Thirty per cent of the patients had a complete remission after a mean follow-up period of 26.9 months. Bullous pemphigoid (BP) is a chronic debilitating autoimmune blistering disease. It is characterized clinically by generalized tense bullae and histologically by subepidermal blisters. Immunofluorescence is crucial in the diagnosis and shows linear deposits of C3 and/or IgG at the basement membrane zone (BMZ). Information regarding this disease in Chinese patients is quite limited. In this study, 86 patients with BP were reviewed. The clinical and histological features, immunofluorescence, modes of therapy and outcome were studied.

The long-term use of immunosuppressive agents may cause profound suppression of the cutaneous immune function. Because epidermal Langerhans cells (LC) play an important role in the cutaneous immune system, they could be the target of immunosuppressants. Since little information is available about the direct immunosuppressive effects of methotrexate (MTX) and azathioprine (AZA) on LC, we studied the viability and immunostimulatory effects of purified LC after pulsation with MTX or AZA at various concentrations. Both MTX and AZA started to suppress the mixed LC-T lymphocyte reaction (MLCLR) significantly at a concentration of 1 microgram/ml. However, the suppressive effect of MTX was not dose-dependent; no further suppression was seen up to a concentration of 1 mg/ml. MTX showed no inhibitory effect on the viability of LC even at concentrations as high as 1 mg/ml. In contrast, the suppressive effect of AZA on the MLCLR was dose-dependent and AZA at a concentration of 500 micrograms/ml or higher markedly decreased the viability of LC. Our study confirmed the immunosuppressive effect of MTX and AZA on epidermal LC. In comparison to MTX, AZA at pharmacological levels showed stronger inhibitory effects on alloantigen-presenting capacity of human epidermal LC and was more cytotoxic to LC. In the therapeutic range, however, MTX and AZA probably have no direct effect on epidermal LC. Our study supports the notion that long-term immunosuppressants deplete cutaneous LC by bone marrow suppression.

Primary cutaneous amyloidosis is a relatively common skin disease in Southeast Asia, South America, and the Republic of China. Although most cases are sporadic, some patients have a family history, suggesting that genetic factors may play a role in its pathogenesis. Some patients with multiple endocrine neoplasia type 2A also have a clinical picture of primary cutaneous amyloidosis. It is thus suggested that the gene of familial primary cutaneous amyloidosis is linked to the pericentromeric region of chromosome 10, the location of the RET proto-oncogene. We have carried out linkage analysis in seven families with cutaneous amyloidosis using four dinucleotide repeat markers from the RET region. Negative lod scores at all recombination frequencies were obtained. We thus conclude that there is no evidence for linkage between Chinese families with primary cutaneous amyloidosis and the pericentromeric region of chromosome 10. The distinct genetic basis, plus their apparent phenotypic differences in sex ratio, age of onset, and sites of cutaneous lesions, suggests that familial primary cutaneous amyloidosis includes clinical subtypes attributable to genetic heterogeneity.

Extramammary Paget's disease (EMPD) is more frequently seen in Caucasian females than in males (3.2:1 female: male ratio). During the past 14 year period, we have collected 22 patients, all Chinese males, with EMPD. They presented with eczema-like lesions in the early stages in the genital or perianal regions. Histological sections showed Paget cells within the epidermis or skin appendages and even within the dermis. No underlying adnexal carcinoma or adjacent internal carcinoma could be detected after thorough examinations. Mode of therapy and outcome are presented. EMPD seems to affect more males than females in Orientals. The incidence of concomitant malignancy in Chinese male patients with genital Paget's disease seems to be much lower than that in Caucasians. However, if EMPD involves the glans penis or perianal area, a search for internal malignancy is still warranted.

Basal cell carcinoma (BCC) is rare on the penis. There have been only 17 cases of penile BCC reported in the literature. Eccrine differentiation may not be uncommon in BCC but has not been reported in penile BCC. We report here a 75-year-old man with multiple penile BCC with histological features of eccrine differentiation. A brief review of the literature is included. Basal cell carcinoma (BCC) is the most commonly diagnosed malignant skin tumour; it probably originates from pluripotential cells in the epidermis or hair follicle. More than 90% of BCCs are located on the head or neck, and its occurrence on the penis is rare. Seventeen cases of penile BCC have been reported in the literature.

Summary Highly enriched and specifically unlabelled human Langerhans cells (LC) from epidermal cell suspensions (ECS) are indispensable for the intensive study of LC function. Discontinuous Ficoll-metrizoate density gradient centrifugation was found to be a satisfactory method of enriching LC from ECS. In contrast to a previous study, however, the majority of LC floated on Ficoll-metrizoate with a density of 1.057 g/cm3 instead of 1.068 g/cm3. The concentration of unlabelled LC can be enriched to as high as 92% from the original 1.8–3.1% LC in ECS. Approximately 40–50% of original LC can be harvested. The procedure was also simplified by using a Schick razor instead of a dermatome to obtain thin epidermal sheets (about 0.25 mm in thickness), omitting the density gradients of 1.089 and 1.10 g/cm3 and using the avidin-biotin complex method to identify LC. LC are non-proliferative cells in in vitro culture systems. The viability of LC dropped to 20–30% after 3 days in the culture medium. It was also observed that LC tended to attach to aggregated keratinocytes in the culture system.

A 10-year-old Chinese boy with the characteristic skin manifestations of dyschromatosis universalis is described. In addition, the patient had congenital nystagmus with poor visual acuity, and ophthalmological examination revealed foveal hypoplasia and albino-like fundi. Histopathology showed giant pigment granules in the skin. Based upon the finding of giant pigment granules in clinically normal skin of the patient's mother, the patient was diagnosed as a case of dyschromatosis universalis with X-linked ocular albinism. To the best of our knowledge, this is the first documented case of this combination.

Tissue culture refers to the propagation of living tissue cells in special media conducive to their growth. Initially devised by Harrison 1 to study frog nerve fiber at the beginning of this century, tissue culture technology has now become an indispensable tool in almost every discipline of biomedical research. Dermatology is by no means an exception. Ljunggren 2 described the growth of skin in amniotic fluid early in 1898, and Lewis 3 observed human epidermal cells in tissue culture with phase-contrast microscopy in 1949. The development of modern methodology for keratinocyte culture did not start, however, until about two decades ago. In 1967, Briggaman et al. 4 prepared a viable suspension of postembryonic human epidermal cells and described their growth characteristics in cell culture. A cell line derived from mouse embryo fibroblasts by Todaro and Green, 5 3T3, was also utilized to promote growth of keratinocytes in culture. Rheinwald and Green 6 showed in 1975 that human epidermal keratinocytes could be cultured selectively on feeder layers of lethally irradiated 3T3 cells. Addition of hydrocortisone, cholera toxin, and epidermal growth factor 7 to the medium has made continued serial subculture possible over many cell generations. By altering the constituents of the medium, Peehl and Ham 8 further cultured keratinocytes from human foreskin successfully without a feeder layer. Various models proposed in recent years 9,10 for growing epidermal cells on a dermal equivalent at the air-liquid interface reflect attempts to more closely approximate physiological conditions in vitro .

Amyloid represents a broad group of chemically unrelated protein complexes that share uniform tinctorial and physical characteristics regardless of different pathogenetic mechanisms. Amyloid has long been identified by its histochemical properties, i.e., crystal violet metachromasia, violaceous appearance with periodic acid-Schiff reaction, positive staining with Congo red and Dylon, and dichroism of Congo red- and Dylon-stained sections on polarization microscopy. It has been further defined by its distinct fibrillar ultrastructures being comprised of 6 to 10-nm thick, straight, nonbranching, nonanastamosing filaments of indefinite length which have a tendency to aggregate as islands and run in random directions.

It has long been recognized that certain characteristic mucocutaneous symptoms and signs may act as important clues in diagnosing the early stage of systemic amyloidosis. Since the first description of clinical cutaneous lesions of primary amyloidosis by Koenigstein 1 in 1925, the spectrum of mucocutaneous manifestations in this disorder has been well documented. 2–7 There is no truly satisfactory classification of systemic amyloidosis; however, systemic amyloidosis could be simply classified as follows: 1.1. Primary systemic amyloidosis: usually no evidence of preceding or coexisting disease but paraproteinemia or plasma-cell dyscrasia can be found. 2.2. Amyloidosis associated with multiple myeloma. 3.3. Secondary systemic amyloidosis: evidence for coexistence of previous chronic inflammatory or infectious conditions. 4.4. Heredofamilial amyloidosis. Based on the result of amyloid protein analysis, Glenner 8 has proposed a more detailed clinical-chemical-pathological classification for human amyloidoses. It appears, however, that this classification is overly complex for clinicians, thus its clinical usage seems rather limited. In primary systemic and myeloma-associated amyloidosis, deposits consist mainly of light-chain (AL) amyloid protein produced as a result of plasma-cell dyscrasia. In a large series of 236 cases of systemic amyloidosis, 4 56% were of primary type and 26% were multiple-myeloma patients. During the period 1978–1987, we have found 14 cases of systemic amyloidosis in our hospital; primary systemic amyloidosis with a type of paraprotein and amyloidosis secondary to multiple myeloma occurred in nine cases (64%) and five cases (36%), respectively. Multiple myeloma associated with amyloidosis has been widely studied in medicine. It has been pointed out that amyloidosis develops in 6–15% of patients with myeloma. 9 In our hospital, five cases (4%) out of 159 myeloma patients showed an association with systemic amyloidosis.

A mass outbreak of poisoning occurred in central Taiwan in 1979 due to the ingestion of rice-bran oil contaminated with polychlorinated biphenyls (PCBs). In addition to PCBs, polychlorinated dibenzofurans (PCDFs) and polychlorinated quaterphenyls (PCQs) were also found in the contaminated oil. The levels of toxic agents in the rice-oil samples collected from factory and school cafeterias and the families of the intoxicated patients were in the range of 53-99 ppm, 0.18-0.40 ppm, and 25-53 ppm for PCBs, PCDFs, and PCQs, respectively. Major components of PCBs and PCDFs in the toxic oil were separated and identified by gas chromatography (GC) and gas chromatography/mass spectrometry (GC/MS) using glass capillary columns. The most toxic PCB reported in commercial PCB preparations, 3,4,3',4'-tetrachlorobiphenyl, was found in the toxic oil as well as in one of the patients' blood and adipose tissue at an early stage of poisoning. The blood samples of 165 patients collected 9 to 18 months after the onset of poisoning contained 10 to 720 ppb of PCBs with a mean value of 38 ppb. One of the most toxic PCDFs, 2,3,4,7,8-pentachlorodibenzofuran, was retained in the liver of a deceased patient. This compound could play an important role in the etiology of PCB poisoning in Taiwan.

A 65-year-old women with systemic amyloidosis was given dimethyl sulfoxide orally for 4 years without significant side effects. Her cutaneous lesions improved markedly after the treatment, and she still survives in satisfactory condition.

1) Basement membrane about 1 μ in thickness separates the hair matrix and dermal papilla. There is spotty alkaline phosphatase activity in the basement membrane. 2) The capillaries in the dermal papilla are surrounded by a characteristic multilayered basement membrane. The plasma in the capillary lumen contains a high concentration of the reaction product of alkaline phosphatase. The basement membrane around the capillary and the plasma membrane of the endothelium and pericyte also show the enzyme activity. No enzyme activity can be seen in the cytoplasm of the endothelium. 3) The cell components in the dermal papilla consist mainly of mesenchymal cells resembling fibroblasts and phagocytes containing melanin granules. The plasma membranes of both kinds of cells are regularly loaded with deposits of alkaline phosphatase. There is also enzyme activity around the melanin granules and in the lysosomes of the phagocytes. The extracellular substance in the vicinity of fibroblasts and phagocytes, including the tropocollagen-precollagen complex, shows alkaline phosphatase activity.

One Chinese construction worker and a Chinese cook experienced unknown insect bites during their stay in Abha of Saudi Arabia and then developed skin ulcers. After returning to Taiwan, Republic of China, they were diagnosed in our hospital as having cutaneous leishmaniasis on clinical and dermatopathologic grounds. We were successful in culturing the Leishmania organism with Tobie medium and liquid metacyclic stage culture medium from the skin ulcers of these two patients. The electron microscopic findings of the parasites, Leishmania tropica, both in the tissue (amastigote) and in the cultured medium (promastigote), were also reported.

In 1979, a mass outbreak of poisoning occurred in Central Taiwan due to the ingestion of rice-bran oil contaminated with polychlorinated biphenyls (PCBs). The major PCB isomers and congeners in the toxic rice oil and in the blood of PCB-poisoned patients were characterized by gas chromatography and gas chromatography/mass spectrometry using a highly efficient glass capillary column. The elimination of some major individual PCBs from blood of these patients was studied. The results indicate that tetra- and pentachlorobiphenyls with adjacent unsubstituted carbon atoms at meta-para positions are rapidly eliminated from the blood of patients, while PCBs with the same degree of chlorination but with adjacent unsubstituted carbon atoms at ortho-meta positions are eliminated more slowly. The results also indicate that most of the hexa- and heptachlorobiphenyls, with adjacent unsubstituted carbon atoms at ortho-meta positions of the biphenyl ring, are eliminated very slowly. Laboratory-animal studies have indicated that PCB excretion depends primarily on the rate of metabolism; therefore these differences in rates of elimination of PCBs should reflect the differences in their rates of metabolism.

A 41-year-old patient with classical manifestations of hyalinosis cutis et mucosae was presented. This rare genodermatosis has mainly been described in Caucasian patients. Our case is the first reported case of hyalinosis cutis et mucosae in a Chinese patient. The patient was given dimethyl sulfoxide orally. The possible mechanism of this therapy is discussed.

We report the successful treatment of lipoid proteinosis in a 41-year-old man using oral dimethyl sulphoxide. The initial dosage was 40 mg/kg/day, which was then increased progressively to 60 mg/kg/day. After 3 years of treatment, the patient's skin lesions, hoarseness of voice and abnormal oesophageal function improved remarkably. No side-effects were noted except for a garlic-like smell on the patient's breath.

A mass outbreak of poisoning occurred in central Taiwan in 1979 due to the ingestion of rice-bran oil contaminated with polychlorinated biphenyls (PCBs), dibenzofurans (PCDFs) and quaterphenyls (PCQs). The incident was called PCB poisoning or Yu-Cheng in Taiwan. The major PCB and PCDF congeners in the toxic oil and in the blood and tissues of the poisoned patients were characterized by gas chromatography and gas chromatography-mass spectrometry using highly efficient glass capillary columns. The levels of toxic agents in the rice oil samples collected from the factory and school cafeterias and the families of the poisoned patients are in the range of 53 to 99 ppm, 0.18 to 0.40 ppm and 25 to 53 ppm for PCBs, PCDFs, and PCQs, respectively. The blood samples of 165 patients collected 9 to 18 months after the onset of poisoning contained 10 to 720 ppb of PCBs, with a mean value of 38 ppb. The blood samples of 10 patients collected 9 to 27 months after poisoning contained 0.02 to 0.20 ppb of PCDFs. Comparative rates of elimination of some PCB congeners from the blood of patients were studied. Various tissues from a patient who died 2 years after poisoning were analyzed for PCBs, PCDFs and PCQs. The intestinal fat contains the highest level of PCBs, while the liver contains the highest concentration of PCDFs. The PCB congeners retained in the tissues either do not have adjacent unsubstituted carbon atoms or have a pair at ortho-meta positions of the biphenyl ring. The major PCDF congeners retained in the tissues were 1,2,3,4,7,8-hexachloro-DF, 2,3,4,7,8-pentachloro-DF and 1,2,4,7,8-pentachloro-DF. The former two congeners, especially 2,3,4,7,8-pentachloro-DF, are very toxic PCDFs; they may play important roles in the etiology of Yu-Cheng.

To the Editor.— Calcinosis cutis may be the most troublesome and debilitating complication in juvenile dermatomyositis. The pathophysiology of this peculiar state is unknown. Treatment, so far, remains unsatisfactory. We report a case of juvenile dermatomyositis with calcinosis cutis that showed remarkable response to orally administered aluminum hydroxide. Report of a Case.— A 13-year-old girl was admitted to our department in August 1986. The patient suffered from multiple erythematous, slightly elevated, papular eruptions over the cheek, trunk, both arms, and both legs, associated with proximal muscle weakness and fever, at the age of 2 years. The diagnosis of juvenile dermatomyositis was made in another hospital, and the patient was treated with low-dose orally administered prednisolone thereafter. In 1982, a flare-up of skin lesions occurred and was followed one year later by multiple yellow-white nodules and plaques protruding over the forehead, back, and upper extremities. On examination, the child appeared with

• Seven patients with lichen amyloidosus were treated with dermabrasion during the last seven years. All patients have had follow-up examinations for at least five years (one patient for seven years). The main symptom, itching, disappeared in all cases, and the clinical results were satisfactory, except for mild hyperpigmentary and depigmentary changes in the treated areas. ( Arch Dermatol 1982;118:302-304)

Thirty cases of lichen amyloidosus were found in a skin clinic during one year. The peak incidence occurred in patients between 40 and 60 years of age. Most cases had long durations, ranging from 5 to 20 years. The extensor surfaces of the limbs were most commonly involved. No evidence of systemic involvement was found.