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Evaluation of ketoconazole.

The pharmacology, microbiology, pharmacokinetics, clinical use, adverse effects, dosage and administration, and drug interactions of ketoconazole are reviewed. Ketoconazole, a new orally active antifungal agent, is an imidazole derivative structurally related to miconazole and clotrimazole. It impairs the synthesis of ergosterol (the main sterol in fungal cell membranes) in susceptible organisms, including yeast (Candida and Cryptococcus spp.), fungi, and dermatophytes. Ketoconazole is absorbed from the gastrointestinal tract; it is better absorbed from acidic aqueous solutions, so drugs that alter the pH of the stomach affect ketoconazole absorption. Therapeutic plasma concentrations are maintained for several hours following ketoconazole administration. Ketoconazole distributes readily into blood, urine, saliva, joint fluid, sebum, and cerumen; recent data indicate it may penetrate into cerebrospinal fluid as well. Elimination is biphasic, with a half-life of two hours during the first 10 hours following a dose, and a half-life of eight hours thereafter. Ketoconazole is metabolized by the hepatic microsomal oxidation system; metabolites are excreted renally. Ketoconazole is effective in treatment of several local and systemic fungal infections. It is approved by FDA for treating candidiasis, chronic mucocutaneous candidiasis, oral thrush, candiduria, coccidioidomycosis, histoplasmosis, chromomycosis, and paracoccidioidomycosis. Ketoconazole has also shown promise in other conditions not yet approved by FDA, including dermatophytosis, pityriasis versicolor, and vaginal candidosis. Controlled, comparative, double-blind trials of ketoconazole versus older agents are generally unavailable. Nausea and vomiting are the most common adverse effects encountered with ketoconazole. Transient elevations in serum liver enzymes have been noted occasionally. Initial daily ketoconazole dosage is 200 mg taken with a meal; 400 mg daily has been used for some conditions. Ketoconazole is a promising new drug, especially when one considers other available antifungal agents. However, large-scale comparative studies are not yet available; a more definitive evaluation of efficacy and safety, especially when the drug is used for long periods of time, must await more widespread use of ketoconazole.

Fungi↗

[Follicular psoriasis with cicatricial alopecia. Piccardi-Lassueur-Graham Little syndrome of a psoriatic nature].

The case of a 21 years old female patient is reported who has had scaly lesions on the scalp since the age of 3, alopecia (later scarring alopecia) since the age of 5, and erythematous and squamous lesions on the trunk and limbs since the age of 14. More recently she developed grouped follicular papules on the trunk, back of the neck and upper limbs. Seven biopsies from the scalp, trunk and sole of foot were performed which showed typical psoriatic changes in all but one, from the scalp, where only scarring alopecia changes could be found. In one lesion from the trunk pseudogranulomatous features were observed in some papillae which were probably due to ectasia, tortuosity and endothelial proliferation of papillary blood vessels. The oral administration of RO 10-9359 was followed by a good remission of the lesions with exception of the scalp alopecia. The differential diagnosis, particularly with pityriasis rubra pilaris and lichen planus, is discussed and the similarities of our case with the Piccardi-Lassueur-Graham Little syndrome emphasised. If one accepts multiple diseases as the cause of the syndrome psoriasis could be admitted as one of them.

Adult↗

[Industrial dermatoses among the Bełthatów brown coal miners].

443 subjects were examined, 235 applying to the physician due to the occurrence of skin dermatoses (group I) and 208 workers referred for periodic examinations (group II). In group I skin dermatoses were found in 100, i.e. 85%, of the subjects and in group II in 99 i.e. 48% of the subjects. In both groups the most frequent dermatosis was feet skin inflammation, especially interdigital intertrigo. Oil acne was diagnosed in 15, ordinary acne in 23, pityriasis versicolor in 19. erythrasma in 10, and eczema and contact dermatitis in 7 subjects of the first group and 3 subjects of the other group. 204 subjects with feet skin pathologies underwent mycologic examinations and 36 subjects--also bacteriologic examinations. The results of those studies indicate that in 23% of the subjects, feet interdigital intertrigo results from mycologic infections. Bacterial infections may contribute to etiopathogenesis. Imidazole compounds are useful for the treatment and prevention of interdigital intertrigo.

Adolescent↗

Tolerability and efficacy of bifonazole in dermatomycoses.

1-[(4-Biphenylyl)-phenylmethyl]-1-H-imidazole (bifonazole, Bay h 4502, Mycospor) is a broad spectrum antifungal agent for the topical treatment of dermatomycoses. In addition to tolerability studies, a report is given on the results of 43 clinical studies of efficacy and tolerability involving 1129 patients in various countries. These were placebo-controlled double-blind studies, randomised comparative studies with reference preparations and open studies. They were carried out with bifonazole cream 1%, solution 1%, gel 1% and powder 1%. 58.6% of the patients tested suffered from dermatophytoses, 21.9% cutaneous candidoses, 14.3% from pityriasis versicolor and 5% from other skin infections. The therapeutic efficacy of bifonazole, assessed according to mycological and clinical findings proved good for the indications studied and administered once daily for a treatment period of 2 or 3 weeks. Tolerability - local and systemic - was good. There was no evidence of substance-related side effects.

Adolescent↗

[The role of clothing in the transmission of pathogenic fungi ].

Laboratory studies were made to examine the possibility of transmission of pathogenic fungi through textiles. 1. Dermatophytes were proven to be present in clothing and leather articles worn over areas infected by fungi. In patients known to be infected with Pityriasis versicolor, contaminated scales were obtained from their textiles, the fungi could be demonstrated. 2. Artificially infected textiles were found to harbor dermatophytes and pathogenic yeasts for a number of weeks without limiting the survival capacity of the fungi. 3. At low temperatures, fungi were not affected by various detergents. Under conditions simulating machine washings (30 minutes exposure time) at a temperature of 60 degrees C any washing agent was sufficient to cause irreversible damage. At higher temperatures the time for killing the fungi was diminished. These results were confirmed by experiments with contaminated material from patients (scales, hairs, nail particles).

Arthrodermataceae↗

[Hyperthermic ulcero-necrotic parapsoriasis "en gouttes" with naso-pharyngeal lesions].

The clinical history of a patient affected by a chronic relapsing eruption is presented. Successive papulopustular, necrotic and ulcerous lesions with fever and general distress appeared. There was no visceral affectation. The case corresponded to the necrotic and hyperthermic parapsoriasis "en gouttes" or acute pityriasis lichenoides as described by Degos and col., 1966. The presence of vasculitis with lymphohistiocytic inflammation invading the epidermis is described. The aspect was similar to the parapsoriasis "en gouttes" pattern even though a biopsy showed the presence of necrotizing angeitis of small vessels, as previously reported. The patient also presented oral and nasopharyngeal ulcerous lesions similar to those found in malignant midline granuloma and Wegener granulomatosis, even though histopathologically different. It is interesting to note the absence of any visceral involvement in a 12 years evolution.

Adult↗

[Non-European open clinical studies on the efficacy and tolerance of ciclopiroxolamine in dermatomycoses (author's transl)].

A survey is given of twenty published open clinical studies carried out outside Europe. They concern the topical action of 6-cyclohexyl-1-hydroxy-4-methyl-2(1H)-pyridone, 2-aminoethanol salt (ciclopiroxolamine, Cic, Hoe 296, Batrafen) in 991 cases of skin disorders, mostly mycoses. 70.7% of the disorders were dermatophytoses, 18.9% candidoses. 6.1% pityriasis versicolor, and 4.2% other skin infections. Four trials were done with 1% Cic cream (o/w-type-emulsion) in 157 dermal disorders and 16 trials with 1% Cic solution (vehicle: polyethylene glycol 400) in 834 cases. Several selected studies are reported in detail, the other are parts of a summarizing survey. After a treatment period which, as a rule, was limited to 3 weeks, the global success rate was 96% (healing and distinct improvement). Any side effects were only seldom recorded.

Adult↗

Sézary syndrome presenting as a follicular dermatosis.

A patient with erythroderma initially characterized by follicular papular dermatosis was diagnosed clinically and histologically as having probable pityriasis rubra pilaris. In addition the patient had an elevated WBC with absolute lymphocytosis. Ninety percent of the lymphocytes had the features of Sézary cells by light and electron microscopy. He was diagnosed as having Sézary's syndrome despite the noncharacteristic findings in the skin biopsy. This case illustrates that Sézary's syndrome can present initially as a follicular dermatosis.

Humans↗

[Radiation therapy of psoriasis and parapsoriasis].

Selective UV-Phototherapy with lambda 300-320 nm (SUP) as well as oral photochemotherapy with 8-methoxy-psoralene plus UVA-radiation (PUVA intern) are very effective in clearing the lesions of th generalized psoriasis and those of the chronic forms of parapsoriasis. Being treated with 4 suberythemal doses per week psoriasis patients are free or nearly free of symptoms after averaging 6.3 weeks of SUP-therapy or after 5.3 weeks of PUVA orally. The PUVA-therapy is mainly indicated in pustular, inverse and erythrodermic psoriasis as well as in parapsoriasis in plaques and variegata. In all other forms of psoriasis and in pityriasis lichenoides chronica, we prefer the SUP-therapy because of less acute or chronic side effects, and because of its better practicability. X-rays are indicated in psoriasis of nails, grenz-rays in superficial psoriatic lesions of the face, the armpits, the genitals and the anal region.

Humans↗

Dermatological problems of onchocerciasis in Nebbi District, Uganda.

A cross-sectional survey of 770 subjects in onchocerciasis hyperendemic villages and 223 subjects from a control community in Nebbi District in the West Nile region of Uganda revealed a high prevalence of onchocercal skin disease of 48% in endemic villages. The most common skin problem was troublesome itching (40%); and the prevalent skin lesions were chronic papular onchodermatitis (16%), depigmentation (4%), lichenified onchodermatitis (2%) and acute papular onchodermatitis (1%). Other typical varieties of onchocercal skin diseases such as, hanging groin, lymphoedema and marked lymphadenopathy were infrequent, and considered rare. Pityriasis vergicolor was the most common non-onchocercal skin lesion in both control and endemic communities, accounting for 37% of all non-onchocercal skin lesions. These skin lesions were associated with a variety of psycho-social and economic impact; and there was a positive correlation between the prevalence of troublesome itching and the prevalence of modules (correlation coefficient r = 0.62, p = 0.00). Given the prospects of onchocerciasis control based on mass ivermectin distribution in communities where blindness is common, we recommend that treatment be extended to communities where blindness is less common, but skin disease known to be predominant.

Adolescent↗

[Cutaneous reactions to gold salts].

OBJECTIVE: Evaluate the clinical features of skin reactions to gold salts. INTRODUCTION: Gold dermatitis is described in the literature as a group of reactions non-specifically associated with these drugs. PATIENTS AND METHODS: Ten patients (7 males, 3 females, mean age 59.6 years [corrected] with a skin reaction were studied over a 6 year period. All were treated with Allochrysine for rheumatoid arthritis (n = 8), rhizomelic pseudopolyarthritis (n = 1) or arthropathic psoriasis (n = 1). RESULTS: The delay to the first signs was from 2 weeks to 8 months. Three lichenoid eruptions (including two with buccal lesions and two which followed an autonomous course), 2 pityriasis rosea (one with eosinophilia and one with liver disease), 2 eczematoid dermatoses and one urticaria were observed. Pathology examinations (8/10) were in agreement with clinical diagnosis. Imputability was 14 (1 case), 13 (8 cases) and 12 (1 case). DISCUSSION: The clinical features observed were variable and in agreement with a particular clinical situation. They were not specific to gold salts and cannot be qualified as "gold dermatitis". Two autonomous and severe lichenoid eruptions were observed. Generalized lesions were associated with biological signs. This situation must be considered as a marker of severity.

Adult↗

Clinical evaluation of clotrimazole. A broad-spectrum antifungal agent.

The efficacy and safety of the broad-spectrum, topically applied antifungal agent clotrimazole were evaluated in two double-blind, multicentric trials. Ten investigators reported on a total of 1,361 cases in which a 1% solution or a 1% cream formulation was compared with its respective vehicle. Clotrimazole was therapeutically effective, as confirmed by mycological cure (negative microscopy and culture) and clinical improvement, in tinea pedis, tinea cruris, tinea corporis, pityriasis versicolor, and cutaneous candidasis. Furthermore, species identification established the efficacy of clotrimazole against Trichophyton rubrum, T mentagrophytes, Epidermophyton floccosum, Microsporum canis, Malassezia furfur (Pityrosporum orbiculare), and Candida albicans. Safety was demonstrated by the low incidence of possibly drug-related adverse experiences, namely, 19 (2.7%) of 699 patients who were treated with clotrimazole, of whom four (0.6%) discontinued treatment.

Candida↗

Lymphomatoid papulosis: a model of lymphomagenesis.

Lymphomatoid papulosis (LyP) is a paradoxical cutaneous lymphoproliferative disorder. Clinically, it resembles the lesions of pityriasis lichenoides and behaves in a benign fashion in most patients. Histologically, it can mimic either Hodgkin's disease because of the presence of large atypical cells resembling Reed-Sternberg cells (type A LyP) or cutaneous T-cell lymphoma because of the presence of cerebriform lymphocytes (type B LyP). A review of this uncommon skin disease is presented here.

Diagnosis, Differential↗

Papulonecrotic tuberculid. A clinical, histopathological, and immunohistochemical study of 15 patients.

We report 10 women and five men with papulonecrotic tuberculid, an uncommon form of cutaneous tuberculosis (TB). The mean age was 22.6 years (range, 2 1/2-35 years) at presentation. The Mantoux test was strongly positive in 13 patients. Five patients showed presumptive evidence of associated TB; in one case, the presence of TB was proven by culture. Response to anti-TB was dramatic in all cases. Clinical findings were similar to those previously published. We emphasize the simultaneous occurrence of erythema induratum, associated Takayasu's disease, possible associated phlebitic tuberculid, and clinical mimicry of acute bacterial endocarditis. The main histopathological findings obtained from 27 biopsy specimens included dermal necrosis (26 of 27 cases), a poorly formed granulomatous infiltrate (27 of 27 cases), vasculitis (11 of 27 cases), perivascular spongy edema (11 of 27 cases), and follicular necrosis or suppuration (five of 27 cases). A Ziehl-Neelsen stain was negative in all biopsy specimens. Immunohistochemical labeling revealed a preponderance of T-lymphocytes (UCHL-1+), monocytes-macrophages (S-100+), and Langerhans cells (ACT+), indicative of a type IV hypersensitivity reaction. B-lymphocytes (L26+) were sparse. Conditions that may be confused with PNT on clinical or histopathological ground include pityriasis lichenoides et varioliformis acuta, papular urticaria, papulopustular syphilide, miliary TB, septicemia, perforating granuloma annulare, chondrodermatitis nodularis, reactive perforating collagenosis, allergic granulomatosis, suppurative folliculitis, and infectious causes of palisading granulomas. Papulonecrotic tuberculid has distinct clinical, histopathological, and immunohistochemical features. Awareness of this entity is important since an appropriate diagnosis is necessary for the institution of timely curative treatment.

Adolescent↗

Pigmentary problems in the tropics.

Pigmentary problems are one of the most frequent causes of dermatologic consultation in the tropics. This article deals with diseases seen mostly in tropical countries (ashy dermatosis, lichen planus pigmentosus, frictional dermatitis, pityriasis versicolor, and pinta) and in which a combination of racial, ecologic, nutritional, and social factors all contribute. Other common dermatoses seen worldwide, such as vitiligo and melasma, sometimes acquire dramatic expressions in tropical countries, and their management is usually difficult even for the most experienced dermatologists.

Dermatitis↗

[One hundred years of cryptococcosis. Medical mycology in the 19th century in Greifswald].

Not later than 1842 medico-mycological investigations began at Greifswald in Germany following the appointment of Wilhelm Baum (1799-1883) to the chair of surgery at the university. This is indicated by some theses as well as by the discovery of the contagious characteristics of pityriasis versicolor by Carl Ferdinand Eichstedt (1816-1892) who found a fungus as the cause (1846), which was named Microsporon furfur later (C. Robin 1853). In 1868 the physician (Karl) Friedrich Mosler (1831-1911) published clinical-mycological studies and investigations on animal feeding with yeasts. Some time later (1870) Friedrich Grohé (1830-1886) and his assistants Alwin R. A. Block (1843-?) and M. R. Roth of the Pathological Institute described results of transmission-studies with "Aspergillus glaucus, Penicillium glaucum and yeast". The successor to the chair, Paul Grawitz (1850-1932), also published results of his own mycological investigations. Finally, on 7 July, 1894, during the 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" followed by the talk of 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 f). Nevertheless, Cryptococcus neoformans has been named in connection with F. Sanfelice, whose results were published later (1895).

Cryptococcosis↗

Differentiation and clonality of lesional lymphocytes in small plaque parapsoriasis.

BACKGROUND: Small plaque parapsoriasis is an idiopathic chronic dermatosis characterized by patches on the trunk and extremities that are often smaller than 5 cm in diameter and that sometimes have a digitate contour. These latter cases are often referred to as digitate dermatosis. Histopathologic examination reveals a mild superficial perivascular lymphocytic infiltrate associated with mild spongiosis and parakeratosis. To characterize this disease more completely, we analyzed the differentiation and clonality of lesional lymphocytes using immunohistologic and molecular biologic methods. OBSERVATIONS: We studied five cases using a frozen-section immunoperoxidase technique. In each case, there was a predominantly CD4+ T-cell infiltrate admixed with CD8+ T cells, Langerhans cells/indeterminate cells, and macrophages. In three cases, the clonality of lesional T cells was studied by denaturing gradient gel electrophoresis of polymerase chain reaction-amplified T-cell receptor-gamma gene rearrangements. Two cases showed a dominant clonal pattern, while one case exhibited a polyclonal pattern. Clinical follow-up disclosed persistent disease in one of the two clonal cases, while lesions in the other clonal case and the polyclonal case gradually resolved. CONCLUSIONS: Our findings indicate that small plaque parapsoriasis is a clinically indolent, histopathologically nonspecific, predominantly CD4+ T-cell-mediated disease that, at least in some cases, contains a dominant T-cell clone. These features put small plaque parapsoriasis into a category with certain other members of the parapsoriasis group, namely, pityriasis lichenoides and lymphomatoid papulosis, which have been shown to be clonal T-cell disorders despite their clinically benign course. It remains to be determined if the dominant T-cell clones identified in some cases of small plaque parapsoriasis can ever be the direct precursors of overt cutaneous T-cell lymphomas.

Adult↗

Hypopigmented mycosis fungoides.

BACKGROUND: Only five cases of purely macular hypopigmented mycosis fungoides have been published in the literature. These patients all had clinical evidence of disease 7 months to 10 years prior to histologic diagnosis, suggesting that this clinical presentation of mycosis fungoides is easily misdiagnosed. OBSERVATIONS: Three African-American males, ages 9, 15, and 22 years, were found to have mycosis fungoides on evaluation of skin biopsy specimens after initially being clinically diagnosed with, and treated for, pityriasis alba. All three had typical histopathologic changes and cell marker studies showing a relative loss of the CD7 antigen, which is normally present on the majority of T cells. One patient who was treated with methoxsalen plus UV light (PUVA) therapy had clearance of his disease clinically and histologically. CONCLUSION: From the literature, it would appear that macular hypopigmented mycosis fungoides is exceptionally rare. This perceived rarity may be inaccurate due to either relative underreporting, incorrect diagnoses, or both. From the eight patients now reported to date, it may be said that hypopigmented mycosis fungoides may be seen in nonwhite individuals and more often than not, has onset before age 20 years.

Adolescent↗