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One hundred years ago: the history of cryptococcosis in Greifswald. Medical mycology in the nineteenth century.

Medico-mycological investigations began at Greifswald in Germany as early as 1842 when Wilhelm Baum (1799-1883) was appointed to the chair of surgery of the university. This is shown by some theses of the time, as well as by the discovery of the contagious nature of pityriasis versicolor by Carl Ferdinand Eichstedt (1816-92), who identified a fungus as the cause (1846), later named Microsporon furfur (C. Robin 1853). In 1868 the physician Karl Friedrich Mosler (1831-1911) published clinical-mycological studies and investigations about animal feeding with yeasts. Some time later (1870) Friedrich Grohé (1830-86) and his assistants, Alwin R.A. Block (1843-?) and M.R. Roth of the Pathological Institute, described the results of transmission studies with 'Aspergillus glaucus, Penicillium glaucum and yeast'. His successor in the chair, Paul Grawitz (1850-1932), also published the results of his own mycological investigations. Finally, on 7 July 1894, at an evening lecture of the Greifswald Medical Society, Abraham Buschke (1868-1943) from the Hospital of Surgery gave a talk 'on a peculiar disease caused by coccidia', which was followed by a talk by the pathologist Otto Busse (1867-1922) on a 'demonstration of a pathogenic coccidia species'. Busse's subsequent publications are the first proper descriptions of cryptococcosis (1894 ff.). However, Cryptococcus neoformans was named after F. Sanfelice, whose results were published later (1895).

Animals↗

Growth inhibition of Malassezia species by pharmacological concentrations of polidocanol.

In vitro antifungal properties of polidocanol (Thesi), a hydroxypolyethoxydecan, were investigated against various yeasts at concentrations of 0.05-10% (w/w) by means of the agar diffusion test; in the case of lipophilic Malassezia furfur, polidocanol-containing olive oil was used additionally for sensitivity study. Six strains of M. furfur of different clinical origin were tested as well as strains of C. albicans (3), C. krusei (3), C. parapsilosis (2), C. robusta (2), Tr. cutaneum (2) and one strain each of C. guilliermondii, C. glabrata, C. tropicalis and M. pachydermatis. Both test systems revealed predominantly fungistatic activity against M. furfur, with a minimal inhibitory concentration (MIC) of 1% polidocanol (w/w), while yeasts of other genera (Candida species, Trichosporum species) showed no or only transitory (C. krusei) inhibition of growth. M. pachydermatis was also found to be sensitive with a MIC of 0.1%; this suggests a specific inhibitory effect against the genus Malassezia. Polidocanol, which has been used for decades as an antipruritic and analgesic in various topical preparations at concentrations between 3% and 5%, might therefore be suitable for prophylaxis of recurrent pityriasis versicolor or in veterinary medicine.

Malassezia↗

Hydrolase activity of 150 Malassezia furfur isolates of different clinical origin.

Apart from pityriasis versicolor, Malassezia furfur is thought to play a significant role in the pathogenesis of seborrhoic eczema and Malassezia folliculitis. However, it has not been clarified whether in addition to host factors (e.g. immune status, greasy skin), yeast-dependent activities are responsible for manifestation of the disease. In this context interstrain variability of hydrolase activity of Malassezia isolates might be significant. For determination of hydrolase activity, washed yeast suspension was applied to selective agar for pathogenic fungi containing 8% (v/v) Tween 80 or Tween 60 and was incubated at 37 degrees C for 10 days. Growth was accompanied by formation of a dense white zone around the colony, in which free fatty acids corresponding to Tween 80 (C18:1) or Tween 60 (16:0, 18:0) were demonstrated by means of thin layer and gas chromatography. Thus, this phenomenon is a parameter for yeast-dependent hydrolysis of Tween 80 and Tween 60. Considering different growth behaviour, a "hydrolase zone' (H2) was determined using the quotient colony diameter/(ring+colony) diameter in each of the 150 strains tested. Although no significant H2 variations were observed in strains of different clinical origin, the present study revealed that in addition to a known enzyme, which is located within the cell wall and/or membrane systems, these Malassezia isolates produce a very active hydrolase diffusing into the medium.

Chromatography, Gas↗

Sulconazole in the therapy of dermatomycoses in Nigeria.

A 1% cream of sulconazole nitrate, an imidazole derivative, was used to treat 38 patients with diverse clinical types of dermatomycoses, including 16 cases of pityriasis versicolor, 14 of dermatophytosis (tinea pedis, tinea cruris, tinea corporis), two of balanoposthitis due to Candida albicans, another two of candidosis of the groin, one each of groin and foot infection due to Trichosporon beigelii and one case each of lesions of the hand and trunk caused by Petriellidium boydii and Scytalidium hyalinum respectively. A complete cure was achieved in 91% of patients, with resolution of the lesions in the majority within 2-4 weeks. There were only two relapses. Sulconazole is recommended as an effective drug for topical treatment of superficial fungal infections of the skin.

Adolescent↗

Drug eruptions with lichenoid histology produced by captopril.

Three cases are presented with a rash due to captopril which, on histology, showed a lichenoid pattern of bandlike upper dermal infiltrate of lymphocytes and histiocytes, together with hydropic degeneration of the basal layer of the epidermis producing Civatte bodies and pigmentary incontinence. The rash presented either as a pityriasis rosea-like picture which appeared about three to six months after the onset of treatment in patients taking low doses, or alternatively, as lichenoid plaques which appeared three to six months after commencement of medication in patients taking high doses. Although both clinical patterns produced a "saw tooth" pattern of the epidermal rete ridges, hypergranulosis and acanthosis were seen only with the lichenoid plaques.

Aged↗

Superficial mycoses in Saudi Arabia.

Between June 1988 and December 1990, 1018 cases of superficial mycoses were investigated. Diagnosis was confirmed by microscopic examination in 503 cases and the causal agent was isolated in 490 cases. Tinea capitis accounted for 47.7% (92.5% in children below 10 years of age). The frequency of other clinical types in descending order was pityriasis versicolor 25.8%, tinea corporis 9%, onychomycosis 5.8%, tinea pedis 4%, intertrigo 3.9% and tinea cruris 2.8%. Erythrasma was encountered three times and mixed piedra and trichomycosis axillaris once. Microsporum canis was the commonest aetiological agent, responsible for 46.9% of ringworm infections. Malassezia furfur was the next most common agent (26.5%) followed by Candida albicans (8.6%) and Trichophyton violaceum (8.2%). Other species were found less frequently. T.simii was isolated from four cases of tinea cruris and one each of tinea capitis and tinea corporis, and Piedraia hortae and Trichosporon beigelii from a case of mixed piedra infection.

Adolescent↗

Survey of cutaneous lesions in Indian newborns.

A total of 900 consecutive newborns delivered at the Nehru Hospital, Chandigarh, India, over a period of 7 months were examined for presence of skin lesions within 48 hours of birth. Commonly observed skin lesions were Epstein pearls (88.7%), mongolian spots (62.2%), milia (34.9%), sebaceous hyperplasia (31.8%), salmon patches (28.4%), and erythema toxicum neonatorum (20.6%). These figures are comparable with earlier reports. Impetigo neonatorum occurred in 11.3% of infants, and was frequent in our hot and humid climate from May to August. Traumatic skin lesions were most often present in babies who had forceps deliveries. Three hundred ten (34%) babies were available for follow-up up to six weeks. Additional skin lesions observed were omphalitis (16 babies), oral thrush (9) and postinflammatory hypomelanosis (8). Three infants had atopic dermatitis, two each had seborrheic dermatitis, diaper dermatitis, pityriasis versicolor, and nevus achromicus. One each had vitiligo, ichthyosis vulgaris, urticaria, and strawberry hemangioma. These observations highlight the importance of repeat examination for the appearance of skin lesions during the neonatal period.

Female↗

Frequency and significance of minor clinical features in various age-related subgroups of atopic dermatitis in children.

The frequency and significance of minor clinical features for the diagnosis of atopic dermatitis (AD) were evaluated in different age-related subgroups of 100 children (up to 12 yrs) with AD and an equal number of controls. Additional features studied were infraauricular fissuring, diffuse scaling of the scalp, and Hertoghe sign. Features found to be nonspecific were ichthyosis, nipple eczema, cheilitis, keratoconus, anterior subcapsular cataract, pityriasis alba, anterior neck folds, and food intolerance. Other minor features were of variable significance in different age groups. Seasonal variation of AD was observed in 44% of patients, with worsening during winter in 29% and in summer in 15%. Of the additional features, diffuse scaling of the scalp and infraauricular fissuring were significant, but Hertoghe sign was not. It was therefore concluded that minor clinical features for the diagnosis of AD need modification, with deletion of some of the present features and addition of newer ones.

Age Factors↗

Epidemiology of skin diseases in school children: a study from northern India.

Little information is available about the prevalence of skin conditions among children in the general population of northern India. Low socioeconomic status, malnutrition, overcrowding, and poor standards of hygiene are important factors accounting for the distribution of skin diseases in developing countries such as India. In order to estimate the burden and relative frequency of dermatologic diseases among children in the community, we measured the point prevalence of skin conditions in 12,586 Indian school children ages 6-14 years. The overall point prevalence of one or more identifiable/apparent skin conditions was 38.8%. Of those studied, 3786 children (30%) had only one skin disease, 765 (6%) had two, and 336 (2.7%) had three skin pathologies. The most common skin conditions and their respective point prevalences were skin infections (11.4%), pityriasis alba (8.4%), dermatitis/nonspecific eczemas (5.2%), infestations (5.0%), disorders of pigmentation (2.6%), keratinization disorders (mostly keratosis pilaris) (1.3%), and nevi/hamartomas (1.1%). This study shows that skin conditions are common in children and about one-third of them are affected at any given time. The finding that more than 85% of the disorders can be grouped into fewer than eight categories is important in designing training programs for medical teams involved in the delivery of primary health care services in developing countries such as India, where about one-third of the population is less than 15 years of age.

Adolescent↗

Prevalence of skin disorders in school children in Ibadan, Nigeria.

Although skin diseases are common in children, there are very few population-based studies in West Africa. Recently, there has been considerable emphasis on hygiene and socio-economic impact on the incidence of allergic disorders in children. We determined the prevalence of skin diseases in a public primary school in Ibadan (southwest Nigeria). A questionnaire for assessing factors associated with the prevalence of diseases was completed, and a complete physical examination was carried out on 1066 students. The study included 529 (49.6%) boys and 537 (50.4%) girls with a mean age of 8.8 +/- 2.5 years. The mean family size of the subjects was 6.7 +/- 2.3 while the mean number of rooms in their homes was 2.6 +/- 1.45. Infectious dermatosis was commonly observed. Of 375 children with a skin lesion, 162 (15.2%) had dermatophytosis, most often tinea capitis, 50 (4.7%) had pityriasis versicolor, and 50 (4.7%) had scabies. Other dermatoses observed included papular urticaria in 35 (3.3%) and angular cheilitis in 27 (2.5%) children. One or more melanocytic nevi were found in 40 (3.8%) children while 138 (12.9%) and 77 (7.25%) had tribal and scarification marks, respectively. Atopic eczema and viral warts were virtually absent. We concluded that fungal infections and scabies were the most common skin diseases in our study population, whereas allergic illnesses were nearly absent.

Adolescent↗

Examination of cutaneous T-cell lymphoma for human herpesviruses by using the polymerase chain reaction.

The etiology of cutaneous T-cell lymphoma remains unknown, although an association with viral infection, in particular certain retroviruses and human herpesviruses, has been suggested. The purpose of this study was to examine skin biopsies of cutaneous T-cell lymphoma for the presence of Epstein-Barr virus, herpes simplex virus type 1 and type 2, and human herpesvirus-6 by using the polymerase chain reaction. Lesional skin biopsies from 30 patients with cutaneous T-cell lymphoma were studied. Control specimens included biopsies from 9 patients with lymphomatoid papulosis and 10 patients with pityriasis lichenoides et varioliformis acuta. DNA extracted from each specimen, as well as from a known positive control for each virus, was examined by using the polymerase chain reaction with viral-specific primers. Each DNA specimen was also amplified with control primers for human beta globin. The specificity of the amplified products was confirmed by Southern analysis. Neither Epstein-Barr virus nor herpes simplex virus was detected in any of the patient specimens examined. Human herpesvirus-6 was detected in one specimen of cutaneous T-cell lymphoma and one specimen of lymphomatoid papulosis. These results do not support a role for any of these herpesviruses in the pathogenesis of cutaneous T-cell lymphoma.

Biopsy↗

Histopathology in erythroderma: review of a series of cases by multiple observers.

This study examines the utility of objective histopathological studies in the evaluation of adult patients with erythroderma. A series of 56 skin biopsies, from 40 erythrodermic patients, was reviewed sequentially by 4 Canadian dermatopathologists who were unaware of clinical details of the cases. The final diagnosis (gold standard), in each instance, had already been determined by others, based on clinicopathologic data and response to therapy. Direct comparison revealed that the mean accuracy of the histopathological diagnoses was 53% (range: 48-66%), a favorable result in view of the difficulty of the task at hand. Additional points of information which evolved from the study are as follows: (i) identification, by microscopy alone, of spongiotic dermatitis, cutaneous T-cell lymphoma and psoriasis, as underlying causes of erythroderma was more successful than that of drug eruptions and pityriasis rubra pilaris; (ii) the epidermotropism which characterizes cutaneous T-cell lymphoma may be mistaken for inflammatory interface changes seen in drug eruptions and vice versa, thus constituting a pitfall in diagnosis; (iii) finally, it appears that submission of multiple simultaneous biopsies, rather than a single specimen, from patients with erythroderma would be likely to enhance the accuracy of histopathological diagnosis.

Adult↗

Evidence that apoptosis and terminal differentiation of epidermal keratinocytes are distinct processes.

Although there are clear parallels between apoptosis and epidermal terminal differentiation it is unclear whether terminal differentiation of keratinocytes is a form of apoptosis. We found that apoptosis was rare in adherent cultures of normal keratinocytes, even when growth factors were removed. When keratinocytes were placed in suspension for 24-96 h the majority of cells were induced to undergo terminal differentiation, as assessed by involucrin expression and cornified envelope assembly, but few cells underwent apoptosis, as assessed by morphological examination, TUNEL labelling and by DNA laddering. Withdrawal of serum and growth factors stimulated apoptosis of suspended keratinocytes but led to some reduction in the number of cells that underwent terminal differentiation. At 96 h the majority of cells retained their nuclei in the presence or absence of serum and growth factors. In normal epidermis only occasional cells within the granular layer had apoptotic nuclei, determined by TUNEL labelling and light and electron microscopy. In affected epidermis of psoriasis, Darier's disease and pityriasis rubra pilaris, diseases characterized by perturbation of growth, differentiation or adhesion, light microscopy revealed no higher proportion of apoptotic nuclei than in normal epidermis. However, the majority of viable epidermal layers in diseased skin were positive by TUNEL labelling, suggesting that TUNEL is not always a specific marker of apoptosis in keratinocytes. We conclude that in vivo and in culture keratinocyte terminal differentiation and apoptosis are distinct cellular events, subject to different stimuli.

Adult↗

Human infections due to Malassezia spp.

The genus Malassezia contains three member species: Malassezia furfur and Malassezia sympodialis, both obligatory lipophilic, skin flora yeasts of humans, and Malassezia pachydermatis, a nonobligatory lipophilic, skin flora yeast of other warm-blooded animals. Several characteristics suggest the basidiomycetous nature of these yeasts, although a perfect stage has not been identified. Classically, these organisms are associated with superficial infections of the skin and associated structures, including pityriasis versicolor and folliculitis. Recently, however, they have been reported as agents of more invasive human diseases including deep-line catheter-associated sepsis. The latter infection occurs in patients, primarily infants, receiving parenteral nutrition (including lipid emulsions) through the catheter. The lipids presumably provide growth factors required for replication of the organisms. It is unclear how deep-line catheters become colonized with Malassezia spp. Skin colonization with M. furfur is common in infants hospitalized in neonatal intensive care units, whereas colonization of newborns hospitalized in well-baby nurseries and of older infants is rarely observed. Catheter colonization, which may occur without overt clinical symptoms, probably occurs secondary to skin colonization, with the organism gaining access either via the catheter insertion site on the skin or through the external catheter hub (connecting port). There is little information on the colonization of hospitalized patients by M. sympodialis or M. pachydermatis. Diagnosis of superficial infections is best made by microscopic examination of skin scrapings following KOH, calcofluor white, or histologic staining. Treatment of these infections involves the use of topical or oral antifungal agents, and it may be prolonged. Diagnosis of Malassezia catheter-associated sepsis requires detection of the organism in whole blood smears or in buffy coat smears of blood drawn through the infected catheter or isolation of the organism from catheter or peripheral blood or the catheter tip. Culture of M. furfur from blood is best achieved with Isolator tubes and plating onto a solid medium supplemented with a lipid source. Appropriate treatment of patients requires removal of the infected catheter with or without temporary stoppage of lipid emulsions; administration of antifungal therapeutic agents does not appear to be necessary. Because many patients who develop Malassezia catheter-associated sepsis have severe underlying illnesses, caution must be exercised in attributing all clinical deterioration to Malassezia infection. Our better understanding of how these organisms cause disease awaits the development of a useful typing scheme for epidemiologic studies and further studies on microbial virulence factors and the role of the immune response in pathogenesis.

Dermatomycoses↗

Involvement of human papillomavirus type 20 in epidermodysplasia verruciformis skin carcinogenesis.

The involvement of human papillomavirus (HPV) in skin carcinogenesis in a patient with epidermodysplasia verruciformis was studied. This patient had disseminated pityriasis versicolor-like lesions, flat warts, and a malignant skin carcinoma. HPV types 3, 17, 20 (HPV-20), and 38 were isolated and molecularly cloned from the benign skin lesions of this patient. Of these HPVs, only HPV-20 was detected in the malignant skin carcinoma. Transcripts of HPV-20 were also expressed in the carcinoma. These findings suggest that HPV-20 was involved in the skin carcinogenesis in this patient.

Adult↗

Novel application of the masson-fontana stain for demonstrating Malassezia species melanin-like pigment production in vitro and in clinical specimens.

Melanin-like pigment produced in vitro and in vivo by Malassezia yeasts has not been described before. Masson-Fontana staining confirmed accumulation of black pigment on the cell walls of L-dihydroxyphenylalaline (L-DOPA)-cultured Malassezia species. Black pigment was also observed in cells and hyphae from hyperpigmented patient lesions with culture-confirmed pityriasis versicolor and seborrheic dermatitis.

Humans↗

Reticulate, patchy and mottled pigmentation of the neck. Acquired forms.

Besides the inherited forms of mottled and reticulate pigmentation, a vast number of diseases and trigger mechanisms can lead to acquired pigmentation of the neck. Nonhereditary variants of reticulate and mottled pigmentation can affect the neck as a typical site and therefore may give a diagnostic clue or it can occur sporadically on the neck as well as on other sites. A well-known and important factor in the pathogenesis is exposure to sunlight. Sun-induced pigmentation often presents on the neck and may result from phototoxic, photoallergic and cumulative actinic damage. Frequent forms comprise berloque dermatitis, Riehl's melanosis, poikiloderma of Civatte and tanning bed lentigines. Different infections may also lead to this distinct skin alteration as pediculosis capitis, pityriasis versicolor and syphilis II. Treatment-induced irregular pigmentations may occur after applications of topical agents (e.g. diphenylcyclopropenone), systemic medication (e.g. 5-fluorouracil, chlorpromazine), as a complication of laser resurfacing or as a chronic graft-versus-host reaction. Different neoplasms may also involve the neck. Widespread pigmented basal cell carcinoma, cutaneous T-cell lymphoma, syringolymphoid hyperplasia and histiocytic diseases may lead to reticulated pigmentation. Various other infrequent conditions as connective tissue diseases, malnutrition, lichen planus pigmentosus and others are summarized. The neck, a readily accessible site to medical inspection, may have an underestimated value for the diagnosis of different skin diseases.

Humans↗