Herpes zoster: daily marking of new vesicles in therapeutic studies. A clinical method for objective assessment of the end of the eruptive phase.

BACKGROUND: The efficacy of a therapeutic agent must be evaluated by objective criteria. However, in herpes zoster (HZ) studies there has been no generally accepted objective clinical criterion. OBJECTIVE: Our purpose was to establish a clinical method for determining objectively the point in time at which the eruptive phase of HZ is completed (no new vesicle formation). This point is said to be a clinical criterion for the end of viral replication in the skin and thus for measuring the efficacy of a virustatic agent. METHODS: Newly formed vesicles were marked with differently colored permanent marker pens each day. This method was evaluated by comparing the results of acyclovir therapy in two groups of patients with HZ. (Group A, no underlying malignancy; n = 9. Group B, underlying malignancy; 64% of these patients were undergoing cytostatic polychemotherapy or had immunodeficiency; n = 22). RESULTS: In both groups, acyclovir stopped the eruption of new vesicles within 1.8 and 2.8 days, respectively (not statistically significant). Group B showed a tendency toward more protracted hematogenous dissemination and a longer duration of therapy. The total duration of the eruptive phase depended solely on the length of the interval between the onset of the HZ and the beginning of therapy. CONCLUSION: The method of marking new vesicles is independent of laboratory facilities, simple, and cost effective; in addition, this method is suitable for statistical evaluation. It is thus superior to other clinical methods for objective assessment of the progression of HZ.

Sequential concentration of chloroquine in human hair correlates with ingested dose and duration of therapy.

Human scalp hair was analyzed for chloroquine using gas-chromatography. In 5 patients it was demonstrated that the amount of uptake of chloroquine into the hair varied proportionally with the dosage (from 500 mg/week to 10 g single dose) and with the time of administration. The chloroquine concentrations ranged from 8 to 1100 micrograms/g hair. Chloroquine could be determined quantitatively after a single toxic dosage used in a suicidal attempt and also after low therapeutic doses. The sequential examination of the hair shaft allows an assessment of the chloroquine amount taken over time, the individual dosage, the initiation and termination of therapy. As hairs can be collected easily, they are a unique specimen for investigation, and it is suggested that they can virtually be used as a "tachogram" of chloroquine drug-therapy or intoxication.

Psoriatic alopecia: acute and chronic hair loss in 47 patients with scalp psoriasis.

Symptomatic hair loss and alopecia were seen in psoriatic lesions of the scalp in 47 patients. Remarkably, in 66% of the cases it was an inaugural manifestation, and in 36% the scalp was exclusively involved. Therefore 34% of the patients presented with a primary manifestation of isolated scalp psoriasis. Hair loss varied in intensity from protracted to moderate and massive (36% in tufts). It presented as acute (51%), chronic (36%) or chronic recurrent (13%). Thirteen patients (28%) became aware of the hair loss with the beginning of therapy. The alopecia was found to be circumscribed in 75% of the cases and diffuse in 25%. In 2 cases psoriatic alopecia also manifested itself at sites other than the scalp. The telogen count was found to be increased up to 25-86% in the florid stage. Examinations under the light microscope showed a patchy perifollicular lymphohistiocytic infiltrate in the upper and middle dermis with adnexotropia in several cases. This infiltrate can alter the follicle epithelium and may lead to a granulomatous foreign-body reaction with destruction of the hair follicle. After topical antipsoriatic treatment, most of the reexamined patients showed complete hair regrowth, while 5 developed a residual scarring. Therefore, in the patient with circumscribed or diffuse symptomatic alopecia, with or without scarring, psoriatic alopecia should be considered.

[Subacute chloroquine overdosage]. / Subakute Chloroquin-Uberdosierung.

Owing to a misunderstanding a 26-year-old man took for malaria prevention 2 tablets (1.0 g) chloroquine daily instead of the recommended dose of two tablets weekly. After 2 weeks he developed vertigo, generalized weakness and, after sun-bathing, severe bullous light reaction. After 4 weeks generalized hair depigmentation occurred. Two weeks later abnormal accommodation and double vision set in so that he lost distant and near vision. All these signs disappeared after the drug was discontinued (vertigo, weakness and abnormal accommodation within 2 weeks; hair regrew in normal colour after 8 weeks). This case shows the whole spectrum of subacute chloroquine overdosage.

[Chloroquine and hydroxychloroquine: side effect profile of important therapeutic drugs]. / Chloroquin und Hydroxychloroquin: Nebenwirkungsprofil wichtiger Therapeutika.

Precise knowledge of the undesirable effects of chloroquine and hydroxychloroquine allows better exploitation of their therapeutic effects. Retinopathy can be avoided by observing a maximum daily dosage of 3.5-4 mg/kg ideal body weight for chloroquine and 6-6.5 mg/kg for hydroxychloroquine. In this way, both can be used for long-term therapy. The pharmacokinetics of chloroquine (storage in deep compartments with long plasma half-life) means that it can cumulate, especially with higher dosages and in the presence of renal or hepatic insufficiency. A high plasma concentration reinforces the side-effects without reinforcing the therapeutic effects. Besides subjective symptoms (e.g. anorexia, diarrhoea, nausea), the following undesirable reactions are significant. On the skin exanthema, hyperpigmentation and photodynamic reactions can develop. The hair can become white in blonde and red-haired men. In the eye, chloroquine deposits in the cornea and disturbances of accommodation can occur, besides retinopathy. Neuromyopathy and central nervous system disturbances (e.g. psychosis) are rare, as is impairment of auditory function or blood cells. During pregnancy there is a risk of potential fetal damage (hearing loss, abortion). An acute overdose is extremely dangerous: the lethal dose is 1 g for children and 4 g for adults. As death occurs rapidly, chloroquine has to be stored where it is absolutely inaccessible to children.

Interleukin-2 in combination with interferon-alpha in disseminated malignant melanoma and advanced renal cell carcinoma. A phase I/II study.

In vitro, the combination of interleukin-2 (Il-2) with interferon-alpha (IFN-alpha) seems to act synergistically on the generation of lymphokine activated killer (LAK) cells. Due to this fact two clinical trials with the combination of Il-2 and IFN-alpha were initiated in malignant melanoma (MM) and renal cell cancer (RCC). Patients with disseminated MM were treated by a sequential application of 10 x 10(6) U/m2 rIFN-alpha 2b s.c. on days 1-7 followed by continuous intravenous infusion of 3 x 10(6) U/m2 rIl-2 on days 8-13 and 15-20. After a pause of 4 weeks the cycle was repeated. In advanced or disseminated RCC, the patients were treated with a daily alternating scheme of 10 x 10(6) U/m2 rIFN-alpha and rIl-2 as 1 h infusion 1 x /day for 14 days. The rIl-2 escalates intra- and interindividually beginning with a dose of 3 x 10(6) U/m2. The cycles were repeated after a pause of 3 and 4 weeks, respectively. The preliminary results show that the schedules are practicable and that the toxicity of the combination of rIl-2 and IFN-alpha does not accumulate. Within the MM group 3/11 evaluable patients achieved partial remission and 2/11 stable disease. In the RCC-group 2/5 evaluable patients achieved partial remission and 2/5 had stable disease so far.

[Psoriatic alopecia manifestation, course and therapy in 34 patients]. / Alopecia psoriatica Manifestation, Verlauf und Therapie bei 34 Patienten.

We report on a long-term clinical study on 34 patients (aged 6 to 88) suffering from psoriasis vulgaris capillitii with ensuing loss of hair and alopecia. Most patients showed heavy hyperkeratosis. The loss of hair was either massive (sometimes in tufts) or moderate; its course was acute in 53%, chronically recurrent in 15%, and chronically progressive in 32% of the cases. The psoriatic alopecia was circumscribed in 80% (from the size of a coin up to that of a palm of a hand; thinned out or bare) and diffuse in 20% of the patients. Alopecia was only observed in psoriatic lesions, but not necessarily in every plaque. Thus, psoriasis of the entire scalp did either result in circumscribed or in diffuse alopecia. The trichogram taken from regions next to alopecic areas revealed a telogen rate between 25 and 86%, according to the respective progression of the disease. The light microscope showed the typical features of psoriasis associated with distinct follicular hyper-(para-)keratosis; in some of the histologic sections, we saw a well-defined perifollicular adnexophilic infiltration of lymphocytes and histiocytes, which could cause alterations of the follicular epithelium and sometimes even destroy it altogether. In due course, these alterations resulted in granulomatous foreign-body reaction with scar formation. After topical anti-psoriatic treatment, we noticed regrowth of hair in more than 70% of the patients, whereas 25% developed scarring alopecia. - What we call psoriatic alopecia is the symptomatic loss of hair in psoriatic lesions of the scalp. In most of the cases, it can easily be identified on account of the underlying psoriasis.(ABSTRACT TRUNCATED AT 250 WORDS)

[Therapy of oral hairy leukoplakia with acyclovir]. / Therapie der oralen Haarleukoplakie mit Acyclovir.

Oral hairy leukoplakia was treated in six patients with (a) acyclovir (i.v. or p.o.), (b) 0.1% vitamin-A acid solution or (c) human beta-interferon-gel (10(5) I.E./g) in a total of 23 therapeutic courses. In 5/6 patients, acyclovir (7.5 mg/kg every 8 h i.v. or 5 x 400 mg p.o. over 5-10 days) led to partial (n = 1) or complete (n = 4) remission. After 1-6 months, however, the leukoplakia recurred in all cases. Vitamin-A acid solution (n = 3) led to remission in one and to improvement in the others. Human beta-interferon gel (n = 3) had no visible effect. The efficacy of acyclovir is further evidence of the concept that the Epstein-Barr virus is a major cause of oral hairy leukoplakia.

[Chloroquine retinopathy: preventable by monitoring the maximum daily dose]. / Chloroquin-Retinopathie: vermeidbar durch Beachtung der maximalen Tagesdosis.

Decisive for the development of chloroquine retinopathy is not the total cumulative dose. Recent findings indicate that retinopathy develops if daily dosages are too high. Therefore, daily dosages of 4 mg chloroquine/kg ideal body weight and 6.5 mg hydroxychloroquine/kg body weight, respectively, should not be exceeded. If these maximum daily dosages are observed, long-term therapy over periods of months or even years seems to be safe.

[Changes in telogen rate, hair density, hair diameter and rate of growth in androgenetic alopecia of the male. Simultaneously a contribution to the significance of dysplastic hair]. / Veränderungen von Telogenrate, Haardichte, Haardurchmesser und Wachstumsgeschwindigkeit bei der androgenetischen Alopezie des Mannes. Zugleich ein Beitrag zur Bedeutung dysplastischer Haare.

In a pilot study, comparative measurements of frontal and occipital trichograms, hair density, hair diameter and hair growth rate were performed on 26 male volunteers (ages 20-33 years) with androgenetic alopecia between stages II and V (Norwood scale). In the frontal region, the proportion of telogen hair was, in general, pathologically higher and increased according to stage. The density of the frontal hair was significantly lower (166 +/- 28/cm2) compared with that of the occipital region (193 +/- 24/cm2) and decreased according to stage. The average hair diameter in the higher Norwood stages decreased similarly in both the frontal and occipital regions, as shown by the correspondence between the two measurement points (frontal, 0.068 +/- 0.011 mm; occipital, 0.069 +/- 0.010 mm). Anagen and dysplastic hair from both the frontal and occipital regions was significantly thicker than telogen hair (0.07 mm vs 0.05 mm). The frontal growth rate (0.355 +/- 0.024 mm/day) was significantly lower than that of the occipital region (0.389 +/- 0.021 mm/day). In addition, the frontal growth rate decreased according to stage. Dysplastic hair exhibited high growth rates and diameters similar to those of typical anagen hair. In our opinion, dysplastic hair is growing hair, the roots of which have been artificially modified by plucking. - These intra-individual comparisons of frontal and occipital regions showed a reduction in the anagen phase, density, diameter and growth rate of the endangered frontal hair. A reduction in the size and dividing activity of the matrix is indicated by our data. It seems that these regressive changes occur primarily without a prior indication of accelerated hair growth.

[Acute exanthematous eruption of multiple Kaposi sarcomas of the AIDS type in a female drug-addict. Successful chemotherapy with vincristine, bleomycin and dactinomycin]. / Akute exanthematische Eruption multipler Kaposi-Sarkome vom AIDS-Typ bei einer drogenabhängigen Frau. Erfolgreiche Chemotherapie mit Vincristin, Bleomycin und Dactinomycin.

In a 30-year-old German women who appeared to be in good general health, numerous Kaposi sarcomas of the AIDS type appeared on her face and trunk within a few days. Her arms, legs and oral mucosa were also affected. The patient has been a prostitute for more than 10 years and an i.v. drug addict for 5 years. Her face and upper trunk were densely covered with livid red tumors that were up to the size of coffee beans, with a longitudinal axis that followed the relaxed skin tension lines. HTLV III antibodies were present. No severe cellular immune defect could be demonstrated (OKT4 + to OKT8 + cell ratio 1.15; later control = 2.4). Recall antigens were negative. Since no severe immune defect was present, cytostatic therapy with vincristine, bleomycin and dactinomycin was carried out. Infiltrates began to regress after just one cycle. After four cycles, the facial lesions had completely disappeared. On the chest slight erythemas remained, but there were no histological signs of Kaposi sarcoma. On the legs there were still some solitary brown infiltrates. It was shown that the AIDS type of Kaposi sarcoma responds to combined chemotherapy.

Severe polyneuropathy in Tangier disease mimicking syringomyelia or leprosy. Clinical, biochemical, electrophysiological, and morphological evaluation, including electron microscopy of nerve, muscle, and skin biopsies.

Polyneuropathy in Tangier disease can be divided into three clinical types. The most severe form (type III) with a syringomyelia-like syndrome has been described in three cases only. Here, a fourth case of this type is presented. Because of unusual trophic disturbances even leprosy was suspected. Electrodiagnostic findings, including evoked cerebral potentials in this case, were suggestive of a generalized neuropathy with some degree of primary or secondary demyelination and implied possible impairment of central structures. Sural nerve biopsy, including electron microscopy and quantitative analysis, revealed a predominant reduction of smaller myelinated and unmyelinated fibres. The main morphological feature was the abundance of abnormal non-membrane-bound vacuoles in Schwann cells, mostly of the unmyelinated type, and in some endoneurial fibroblasts, macrophages and perineurial cells. There was no inverse relationship between lipid vacuoles and axons in Schwann cell complexes as suspected by others. An excess of endoneurial collagen as well as an increased fascicular area were obvious. In five skin biopsy specimens of different regions typical vacuoles were noted in Schwann cells, histiocytes, nevus cells, and rarely in perineurial cells.

["Minute therapy" of psoriasis with dithranol and its modifications. A critical evaluation based on 315 patients]. / Die "Minutentherapie" der Psoriasis mit Dithranol und ihre Modifikationen. Eine kritische Wertung anhand von 315 Patienten.

A total of 315 psoriasis patients were treated on the basis of short-contact "minutes" therapy: 230 with 0.1-3% dithranol-2% salicylic acid-white soft vaseline (DSV) for 10-20 min daily; 85 patients in left-right comparison with modified therapeutic schemes. The object was to study the influence of concentration, contact time, psoriasis type, self-treatment at home, frequency of application, ointment base, and the admixture of corticosteroids on the efficacy of "minutes therapy." The clearing quotient for the individual psoriasis types was varied; it reached on an average 75% with a treatment period of 29.4 days. Even lower dithranol concentrations below 1% proved efficacious with part of the patients. Self-treatment at home and irregular applications diminished the efficacy. Neither prolongation of the contact time to 1 hr nor the addition of corticosteroids to dithranol did anything to improve the therapy results. The relapse-free period averaged 3.9 months. Undesirable irritation was avoided to a great extent by adjustment of the treatment intensity to individual tolerances. The simultaneous application of dithranol and corticosteroids did not hinder or diminish the dithranol erythema. For additional safety, a preliminary test treatment can be confined to a limited area for 1 week. Fortunately, the staining due to dithranol brown can be reliably removed from certain textiles and from the bath tub or shower cabin by the use of hypochlorite.