Acquired hyalinosis cutis et mucosae in plasmacytoma with monoclonal IgG-lambda gammopathy

A 66-year-old female patient developed within 2 years clinical symptoms of hyalinosis cutis et mucosae due to a plasmocytoma with monoclonal IgG-light-chain gammopathy. The clinical diagnosis was supported by light- and electron-microscope studies. The form of hyalinosis cutis et mucosae described by Urbach and Wiethe is a genetic disease with its onset in early childhood. For this reason, we propose the designation "acquired hyalinosis cutis et mucosae" for the case reported here.     

Hyalinosis cutis et mucosae--a case report

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.     

Hyalinosis cutis et mucosae (Urbach-Wiethe) in 2 sisters

The authors report on 2 sisters who had suffered from both atopic eczema and hoarseness since their birth. Rough, yellowish-white papular deposits in the skin and the oral mucosa had developed during their childhood. The clinical diagnosis of hyalinosis cutis et mucosae was confirmed in both cases by means of histology and electron microscopy.     

Corrective dermatosurgery in childhood--own experience

Congenital and acquired lesions on children's skin impose great burden upon the children and their parents. These children are frequently faced with various kinds of embarrassment in communication with their peers, ranging from sneering and mockery to isolation. That is why these lesions, especially if readily observable, should be completely removed or at least corrected as soon as possible to enable the child to establish normal communication with the environment and to prevent psychic trauma that may entail serious consequences later in life. Seven pediatric patients burdened with such lesions are presented (naevus papillomatous et verrucosus colli, atrophia linearis cutis faciei, naevus hyperkeratoticus systemicus dorsi, ichthyosis nigra, poikiloderma congenitum, hyalinosis cutis et mucosae, and alopecia post combustionem). Dermabrasion was used in six patients, whereas occipital hair graft transplantation to the alopecic sites was used in a girl with posttraumatic alopecia.     

Late onset hyalinosis cutis et mucosae

Two cases of non-familial, late onset (50 and 62-years-old) hyalinosis cutis et mucosae were studied and compared with classical early onset cases. Late onset cases showed essentially the same histological and ultrastructural features described for early onset cases. The late onset variety should be distinguished from other diseases; they resemble systemic amyloidosis and sometimes the adult form of colloid milium.     

Selected disorders of connective tissue: pseudoxanthoma elasticum, cutis laxa, and lipoid proteinosis

There has been progress made in the understanding of 3 Mendelian disorders: pseudoxanthoma elasticum, cutis laxa, and lipoid proteinosis cutis and mucosae. While they are primary connective tissue diseases, their names imply a connection to the skin, and in fact, it is often the dermatologist who makes the diagnosis. It seems rational that defects in various extracellular matrix proteins cause lipoid proteinosis or subtypes of cutis laxa, yet the discovery of a liver- and kidney-based transmembrane transporter as the culprit of pseudoxanthoma elasticum was rather surprising and may shed new light on elastic tissue homeostasis.     

Familial benign chronic pemphigus (Hailey-Hailey disease): successful treatment with carbon dioxide laser

Hailey-Hailey disease is a rare, autosomal dominantly inherited genodermatosis, which manifests with recurrent intraepidermal blistering and erythematous hyperkeratotic patches in intertriginous areas. Conventional therapeutic approaches include topical and systemic steroids, antibiotic agents, as well as oral retinoids. Alternative treatments include surgical interventions such as excision, dermabrasion and laser ablation. A 56-year-old woman presented with 15-year history of severe therapy-resistant Hailey-Hailey disease. We performed laser ablation with carbon dioxide laser under general anesthesia. Six weeks after treatment complete remission within ablated areas was achieved. Six-month follow-up showed no relapse. In our opinion carbon dioxide laser ablation represents an effective and safe therapeutic option for Hailey-Hailey disease.     

Efficacy of oral retinoids for keratoacanthoma centrifugum marginatum

Keratoacanthoma centrifugum marginatum (KCM) is a rare variant of keratoacanthoma. This condition is difficult to diagnose because of its large size and expansive nature and may be diagnosed as a malignant tumor. There are various treatments such as surgery and oral retinoids; however, limited studies have verified their effectiveness. Here, we report a case of KCM on the anterior chest of a 50‐year‐old woman and evaluate the efficacy of oral retinoids. In this case, oral retinoids were highly effective for KCM treatment. A total of 55 cases of KCM, including 54 previously reported cases, were reviewed, and their clinical characteristics and treatment were examined. In this report, 14 of 16 patients were effectively treated with oral retinoids, resulting in a treatment rate of 87.5%. Furthermore, even low‐to‐medium doses were sufficient for treatment and prevention. KCM can be misdiagnosed as a malignant disease based on its clinical features. Due to its large size and expansive nature, a wide excision may be performed; however, because oral retinoids have a very high response rate, an accurate diagnosis will help avoid an unnecessary wide excision.     

Hyalinosis cutis et mucosae (Urbach-Wiethe disease)--ultrastructural and immunological characteristics

In this report on a young female patient with hyalinosis cutis et mucosae (Urbach-Wiethe disease, lipoid proteinosis), we present the clinical, immunological and ultrastructural features of this inherited disorder and discuss the differential diagnosis against other interstitial connective tissue depositions. Immunologically, the most important result was the increased amount of collagen type IV at the junction zones of epidermis, dermal vessels and appendages. This was in accordance with the ultrastructural deposition of hyalin material, mainly consisting of multiplied basal laminae at the respective junction zones. The pathogenesis (gene defect or defective gene regulation?) and therapy are discussed.     

Clinical and molecular abnormalities in lipoid proteinosis

Lipoid proteinosis (hyalinosis cutis et mucosae) is a rare, autosomal recessive disease. The main clinicopathological features comprise skin and mucous membrane infiltration and scarring with deposition of hyaline material. In this report, we describe a 6-year-old boy in whom a diagnosis of lipoid proteinosis was first suspected when he presented with blisters and erosions at 4 years, a history of life-long dysphonia and a previous epileptic convulsion. The diagnosis was confirmed by histology and identification of a homozygous frameshift mutation, 501insC, in exon 6 of the gene encoding extracellular matrix protein 1, ECM1. Lipoid proteinosis may show protean clinical features and be difficult to diagnose on clinical grounds alone. This case report illustrates that lipoid proteinosis may show protean clinical features and yet remain undiagnosed for many years. Although the gold standard for definite diagnosis remains histology, molecular characterisation of the gene mutation will add to our understanding of genotype-phenotype correlation and perhaps to the development of a rationale for future therapeutics.     

The molecular basis of lipoid proteinosis: mutations in extracellular matrix protein 1

Lipoid proteinosis (OMIM 247100), also known as Urbach-Wiethe disease or hyalinosis cutis et mucosae, is a rare autosomal recessive disorder characterized by generalized thickening and scarring of the skin and mucosae. In 2002, the disorder was mapped to a locus on chromosome 1q21 and pathogenic mutations were identified in the ECM1 gene, which encodes for the glycoprotein extracellular matrix protein 1 (ECM1). ECM1 has since been shown to have several important biological functions. It has a role in the structural organization of the dermis (binding to perlecan, matrix metalloproteinase-9 and fibulin) as well as being targeted as an autoantigen in the acquired disease lichen sclerosus. ECM1 also shows over-expression in certain malignancies and is abnormally expressed in chronologically aged and photo-aged skin. Thus far, 26 different inherited mutations in ECM1 have been reported in lipoid proteinosis. In this article, we provide an update on the molecular pathology of lipoid proteinosis, including the addition of 15 new mutations in ECM1 to the mutation database, and review the biological functions of the ECM1 protein in health and disease.     

Combined retinoid plus surgical treatment of hypertrophic Darier's disease

A 28-year-old male with severe hypertrophic Darier's disease was successfully treated with a combination of retinoids, dermabrasion and surgical excision. No recurrences have been noted after a follow up of 2 years.     

Behçet's disease

A 29-year-old man presented with oral and genital ulcers, erythematous papules and pustules on his back and chest, and deep vein thrombi. A diagnosis of Beh?et disease was made. Beh?et disease is a relapsing disorder that affects the mucocutaneous surfaces. It presents usually as ulcers on the orogenital mucosae, but can also present as an acneiform eruption. The International Study Group on Beh?et disease has established criteria that consist of oral and genital lesions, ocular involvement, skin findings, and a pathergy. Treatment of choice is colchicine or prednisone.     

Elektronenmikroskopische Befunde des Hyalins bei Hyalinosis cutis et mucosae. Gleichzeitig ein Beitrag zur Frage der Entstehung des Hyalins

Zusammenfassung Bei einem Kranken mit Hyalinosis cutis et mucosae wurde das Hyalin elektronenmikroskopisch untersucht. Es läßt sich als ein nicht orientiertes Flechtwerk feiner Filamente in breiten mantelartigen Schalen um Gefäße darstellen. Die Basalmembran ist lamellär einbezogen. Einzelne kollagene Fasern finden sich im Hyalin eingebaut. Es bestehen räumliche Beziehungen zu Fibroblasten.In Analogie zu neueren pathogenetischen Vorstellungen beim Amyloid wird auch beim Hyalin die primäre Veränderung am Ort der Ablagerung selbst vermutet und die Transsudation von Plasmaeiweißen als sekundär und fakultativ im Sinne des Schlammfangs gedeutet.

---

Electron microscopic investigation of hyaline in hyalinosis cutis et mucosae (lipoid-proteinosis urbach-wiethe)

Summary Electron microscopic investigation of hyaline in a patient with lipoid-proteinosis (Urbach-Wiethe) revealed a non-orientated network of thin filaments broadly coating the blood vessels and including the laminated basal membrane. Isolated collagen-fibrils were found in the hyaline. Spatial connection to fibroblasts could be detected.In analogy to more recent views about the pathogenesis of amyloid it is suggested that in hyalinosis, too, the primary changes seem to be located at the side of the deposits and transsudation of plasma-proteins is secondary and facultative.

---

---

Herrn Prof. Dr. J. Tappeiner zum 60. Geburtstag gewidmet.     

Medikamentöse Therapie der Akne

Acne is treated according to the clinical picture and the pathophysiologically relevant mechanisms, such as seborrhea, follicular hyperkeratosis, P. acnes colonisation,and inflammation. In mild forms of acne, topical therapy is most appropriate. Comedonal acne can be treated with topical retinoids; papulopustular acne with a combination of retinoids and topical antimicrobial substances (benzoyl peroxide, antibiotics, or azelaic acid). Moderate forms or those with extrafacial involvement can be treated with oral antibiotics combined with topical retinoids or benzoyl peroxide. Acne conglobata and other severe manifestations are treated with oral isotretinoin. Women are also treated with oral contraceptives containing anti-androgenic progestins. If inflammation is prominent, initial short term treatment with oral glucocorticoids is helpful. Second-line agents include oral zinc or dapsone. Following successful treatment, topical retinoids are suitable for maintenance therapy.     

Hyalinosis cutis et mucosae

Hyalinosis cutis et mucosae is a rare autosomal recessive disorder which is characterized by deposition of hyaline material around the basement membrane of the skin and mucous membranes. Typical clinical symptoms are hoarseness, infiltration of the mucous membranes and papular verrucous skin changes. Mutations within the extracellular matrix protein gene (ECM‐1) are the underlying defect.We report on a 24‐year‐old man, who had first been seen inour department at the age of seven and had undergone the necessary diagnostic procedures and who revisited 17 years later with hoarseness and extensive verrucous skin changes at elbows and knees which were removed by excision. A new mutation of the ECM1 gene was identified.     

HISTOGENESIS OF HYALINOSIS CUTIS ET MUCOSAE

Light microscopically, reticulum fibers and argyrophilic materials were found by reticulum staining, and lipid droplets by Sudan III staining, around the blood vessels and in the interstices of the smooth muscle fibers of tunica dartos; toluidine blue staining of thick sections of Epon-embedded tissue revealed poorly-stained, glass-like, amorphous hyalin with configuration of collagen fibers in the same areas and hyalinized muscle fibers in tunica dartos. Electron microscopy disclosed that multiplication of the basal lamina and its transition to the fibrogranular amorphous material, probably a hyalin substance, was seen around the true smooth muscle cells of tunica dartos and also around the blood vessels. In addition, dilated rough-surfaced endoplasmic reticulums with fibrogranular content were often observed in the endothelial cells, pericytes, and smooth muscle cells, with Golgi apparatus in some parts. These findings suggest that hyalinosis cutis et mucosae is due to the accumulation and invasion of hyalin into the normal collagen fibers due to a genetic abnormality in the synthetic processes of smooth muscle cells, vascular endothelial cells, pericytes and some fibroblast-like connective tissue cells. In my speculation, the hyalin substance in this disease may be normal collagen invaded by basal lamina glycoprotein, most probably involving type III and/or type IV collagen.     

Leukemia cutis - epidemiology, clinical presentation, and differential diagnoses

Leukemia cutis is an extramedullary manifestation of leukemia. The frequency and age distribution depend on the leukemia subtype. The clinical and morphological findings have a wide range of cutaneous manifestations and may present with nodular lesions and plaques. Rare manifestations include erythematous macules, blisters and ulcers which can each occur alone or in combination. Apart from solitary or grouped lesions, leukemia cutis may also present with an erythematous rash in a polymorphic clinical pattern. Consequently, leukemia cutis has to be distinguished from numerous differential diagnoses, i. e. cutaneous metastases of visceral malignancies, lymphoma, drug eruptions, viral infections, syphilis, ulcers of various origins, and blistering diseases. In the oral mucosa, gingival hyperplasia is the main differential diagnosis. The knowledge of the clinical morphology is of tremendously importance in cases in which leukemia was not yet known.     

The rationale for using a topical retinoid for inflammatory acne

Both comedogenesis and the development of inflammatory lesions in acne vulgaris appear to be related to genetic as well as immune processes. The key regulatory cytokine, interleukin-1alpha, has recently been documented as playing a major role in both the hypercornification and the orchestration of immune factors, ultimately resulting in noninflammatory and inflammatory lesions. Topical retinoids, such as tretinoin, and topical retinoid analogs, such as adapalene and tazarotene, help normalize the abnormal follicular keratinocyte desquamation - a key pathophysiologic factor in comedogenesis. This normalization also helps mitigate against the development of a propitious microenvironment for Propionibacterium acnes. Preclinical data suggest that topical retinoids and retinoid analogs may also have direct anti-inflammatory effects. A wealth of clinical data confirms that topical retinoids and retinoid analogs significantly reduce inflammatory lesions. Comparative clinical trials also demonstrate that adapalene has the best cutaneous tolerability profile of all these agents. Optimal therapy for inflammatory acne would involve the use of topical retinoids or retinoid analogs combined with oral or topical antibacterials.