Chronic cutaneous sclerodermoid graft-versus-host disease: evaluation by 20-MHz sonography.

BACKGROUND: Chronic graft-versus-host disease (GVHD) is an immunological disorder frequently occurring as a late consequence of allogeneic bone marrow transplantation. Two variants, cutaneous lichenoid and sclerodermoid, have been described, based on clinical and histopathological examinations. It is, however, difficult to determine non-invasively the degree of cutaneous GVHD in vivo. Ultrasonographic methods have recently provided us with the means for objective and non-invasive monitoring of the dynamics of many chronic skin diseases. AIM, PATIENTS AND METHODS: In five patients with chronic cutaneous sclerodermoid GVHD skin thickness was measured with a 20-MHz B-mode ultrasound scanner (DUB 20S, taberna pro medicum, Lüneburg, Germany) in a clinically well-defined target skin lesion. Additionally cutaneous GVHD was assessed histologically before and after treatment. RESULTS: In all patients before treatment the corium of sclerotic skin was thicker than the corresponding areas of healthy skin. The skin thickness was increased from 45% to 83%. In the subcutaneous tissue proper echo-rich reflexes were prominent, representing the correlate of subcutaneous fibrotic trabeculae. In all patients ultrasonographic evidence of regression was shown (decrease of skin thickness by 18-83%). Moreover, it was demonstrated that quantitative assessment of skin thickness is feasible. CONCLUSIONS: In this paper we describe the detailed sonographic features of cutaneous sclerodermoid GVHD for the first time. As the method is simple and non-invasive, repeated examinations are possible. This provides the basis for monitoring treatment effects and efficient follow-up in these chronically progressive clinical conditions after bone marrow transplantation.

[Death after bee-sting]. / Tod nach Bienenstich.

A ten-year-old girl collapsed on the street with the signs of acute anaphylaxis. Cardiopulmonary resuscitation was unsuccessful. At the autopsy a thorn-like object was found sticking in the tongue and was later identified as the stinger of a honey bee. Witnesses reported that the girl had drunk some ice tea from a box and then had complained about pains in the mouth. Postmortem blood tests revealed increased total IgE level as well as increased levels of specific IgE against bee and wasp poisons. Cause of death was a bronchospasm caused by an allergic reaction due to a sting of a honey bee.

Allergic contact dermatitis from natural latex.

BACKGROUND: Reports on natural latex allergy have increased steadily during the last 10 years. Latex allergy generally refers to a type 1 reaction to natural rubber latex (NRL) proteins with clinical manifestations ranging from contact urticaria to asthma and anaphylaxis. Previous United States studies on NRL allergy largely have been reported by allergists with little detailed information on hand eczema, contact allergy, or on outcome. The present study was performed from March 1998 to November 1999 with the aim of finding out the prevalence of type IV hypersensitivity to latex in patients with suspected rubber allergy. MATERIALS AND METHODS: A total of 167 patients with hand eczema and contact with rubber products underwent patch testing with the standard screening and rubber components (test series Deutsche Kontaktallergiegruppe), and NRL pure provided by Regent (liquid high ammonia 0.7% NRL, accelerator, and preservative-free latex) between March 1998 and November 1999. The charts of all NRL positive patients are reported with the results of history, prick, patch tests, total IgE, specific IgE to latex (FEIA) test and follow-up data (after 6 months). RESULTS: Four patients (3 men) showed positive patch test results to NRL. One of these patients also reacted to the rubber chemical tetraethylthiuram monosulfide, and another one of these patients revealed a type 1 reaction to NRL, diagnosed by positive reaction to prick test. The other 3 patients with patch test reactions to NRL had negative reactions to prick tests to NRL extracts after 20 minutes. All 4 patients had a positive delayed prick test reaction to NRL. Latex FEIA test result was negative in all 4 patients. The contact eczema healed after elimination of the latex gloves and medical latex devices in all patients. Furthermore, 10 of the 167 patch testing patients (6%) were positive for tetramethylthiuram monosulfide 1%. CONCLUSION: In the present study with 167 patients, the prevalence of type IV hypersensitivity to latex was 2.4%. We recommend that the patch test with NRL as well as with rubber additives should be performed in patients of suspected contact dermatitis caused by rubber products.

[Subcutaneous calcifications after radiotherapy]. / Subkutane Kalzifikationen nach Strahlentherapie.

A 75-year-old female patient presented with late stage cutaneous radiation syndrome, following postoperative combined radiotherapy for cervical carcinoma administered 32 years ago. She was hospitalized because of a deep abscess in the radiation-exposed area on the sacrum. Extension into the subcutaneous fibrosis was verified by 7,5-MHz-sonography and nuclear magnetic resonance imaging. With intravenous cefotiam (Spizef) 2.0 g three times daily, the inflammation decreased, as seen clinically and with nuclear magnetic resonance imaging. As a secondary finding, an unusual distinctive subcutaneous calcification was diagnosed in the radiation-exposed area by means of 7,5-MHz-sonography, as well as computer- and nuclear magnetic resonance imaging. These subcutaneous calcifications are most likely to have been radiation-induced.

[Allergic contact dermatitis in beauty parlor clients]. / Allergische Kontaktdermatitis bei Friseurkunden.

Occupational contact dermatitis in hair dressers and beauticians has increased in importance in the past years. Type IV-allergies against glyceryl monothioglycate components of permanent waves are most common. Other occupational allergens include bleach components such as ammonium persulfate and hair dye ingredients such as p-phenylenediamine (PPD) and p-toluylene-diamine (PTD) base. Allergies to hair dyes in customers of hair dressers have rarely been observed. Two female patients developed allergic contact dermatitis of the scalp and face after repeated use of Polycolor intensivtönung schwarz and of Movida color. We also review the current literature on type IV-allergies to components of hair dressing products components.

Interferon-gamma in 5 patients with cutaneous radiation syndrome after radiation therapy.

BACKGROUND: Irradiation can cause acute inflammatory responses as well as chronic fibrotic alterations of the skin. Cutaneous radiation fibrosis evokes a complex of therapeutic problems. However, therapeutic options, apart from surgical approaches, are limited. PATIENTS AND METHODS: Five female patients suffering from severe cutaneous fibrosis were treated with interferon-gamma on a low-dose regimen, 3 x 100 microg/week subcutaneously for 6 months, then once per week for another 6 months. In 4 patients, skin thickness was measured with high-frequency (20 MHz) ultrasound in a clinically well-defined target skin lesion. In 1 patient, nuclear magnetic resonance imaging was performed to quantify the extent of cutaneous radiation fibrosis and to monitor the therapeutic outcome. RESULTS: All patients suffered from radiation-induced cutaneous fibrosis. Additionally, in 1 patient, a fistula, as assessed by lymph vessel scintigraphy, and in another patient a radiation ulcer was diagnosed. In all patients, reduction of radiation-induced fibrosis could be documented. Both fistula and radiation ulcer regressed completely under interferon-gamma therapy. CONCLUSION: Low-dose interferon-gamma therapy is a new and effective treatment modality for cutaneous radiation fibrosis caused by radiation therapy. The positive impact of interferon-gamma on our patients warrants randomized double-blind trials on therapy of radiation fibrosis.

The outcome of local radiation injuries: 14 years of follow-up after the Chernobyl accident.

The Chernobyl nuclear power plant accident on April 26, 1986 was the largest in the history of the peaceful use of nuclear energy. Of the 237 individuals initially suspected to have been significantly exposed to radiation during or in the immediate aftermath of the accident, the diagnosis of acute radiation sickness (ARS) could be confirmed in 134 cases on the basis of clinical symptoms. Of these, 54 patients suffered from cutaneous radiation syndrome (CRS) to varying degrees. Among the 28 patients who died from the immediate consequences of accidental radiation exposure, acute hemopoietic syndrome due to bone marrow failure was the primary cause of death only in a minority. In 16 of these 28 deaths, the primary cause was attributed to CRS. This report describes the characteristic cutaneous sequelae as well as associated clinical symptoms and diseases of 15 survivors of the Chernobyl accident with severe localized exposure who were systematically followed up by our groups between 1991 and 2000. All patients presented with CRS of varying severity, showing xerosis, cutaneous telangiectasias and subungual splinter hemorrhages, hemangiomas and lymphangiomas, epidermal atrophy, disseminated keratoses, extensive dermal and subcutaneous fibrosis with partial ulcerations, and pigmentary changes including radiation lentigo. Surprisingly, no cutaneous malignancies have been detected so far in those areas that received large radiation exposures and that developed keratoses; however, two patients first presented in 1999 with basal cell carcinomas on the nape of the neck and the right lower eyelid, areas that received lower exposures. During the follow-up period, two patients were lost due to death from myelodysplastic syndrome in 1995 and acute myelogenous leukemia in 1998, respectively. Other radiation-induced diseases such as dry eye syndrome (3/15), radiation cataract (5/15), xerostomia (4/15) and increased FSH levels (7/15) indicating impaired fertility were also documented. This study, which analyzes 14 years in the clinical course of a cohort of patients with a unique exposure pattern, corroborates the requirement for long-term, if not life-long, follow-up not only in atomic bomb survivors, but also after predominantly local radiation exposure.

[Cutaneous radiation syndrome: clinical features, diagnosis and therapy]. / Das kutane Strahlensyndrom. Klinik, Diagnostik und Therapie.

Accidental exposure to ionizing radiation may occur during such catastrophic events as the Chernobyl accident in 1986 or over days to weeks as in Goiania in 1987 and in the military camp during the training of soldiers in Lilo/Georgia in 1997, as well as in medical institutions. The cutaneous symptoms after radiation exposure are based on a combination of inflammatory processes and alteration of cellular proliferation as a result of a specific pattern of transcriptionally activated proinflammatory cytokines and growth factors. They follow a time course consisting of prodromal erythema, latency period, acute stage, chronic stage and late stage. The entire complex is referred to as cutaneous radiation syndrome. The time course depends on several factors such as the radiation dose, radiation quality, individual radiation sensitivity, the extent of contamination and absorption and amount of skin exposed. For the diagnosis of the cutaneous radiation syndrome the following procedures are used: 7.5 MHz to 20 MHz-B-scan sonography, thermography, capillary microscopy, profilometry, nuclear magnetic resonance imaging, bone scintigraphy and histology. Based on the results of experimental and clinical research, today treatment may include topical or systemic corticosteroids, gamma-interferon, pentoxifylline, vitamin E and superoxide dismutase. The treatment depends on the stage of the cutaneous radiation syndrome. Due to the complexity of the clinical manifestations of radiation disease, most patients require interdisciplinary treatment in specialized centres. Dermatologists are essential partners in the life-long follow-up and therapy of such patients.

Eosinophilic fasciitis treated with psoralen-ultraviolet A bath photochemotherapy.

Eosinophilic fasciitis is a rare disorder which can markedly affect the quality of life in individual patients. So far, no generally accepted and effective treatment modality has been available. Although the precise nature of eosinophilic fasciitis is still unknown, it is often regarded as a variant of localized scleroderma (morphoea). Phototherapy and photochemotherapy have been shown to be effective in the treatment of sclerodermatous skin lesions. We report a patient with eosinophilic fasciitis which was successfully treated with psoralen plus ultraviolet A bath photochemotherapy within 6 months.

Accidental radiation exposure and azoospermia.

Seven Georgian male soldiers (19-25 years old) had accidentally been exposed to radiation by Cs-137 between April 1996 and May 1997. No information about the exact time and duration of exposure was available. All patients presented with the subacute stage of Cutaneous Radiation Syndrome with deep painful ulcers on different body sites, predominantly on the legs. Semen analyses showed complete azoospermia in 4 patients, with elevated follicle-stimulating hormone (FSH) in 3 and elevated luteinizing hormone (LH) in 2 of them. One patient had severe oligozoospermia of 7 million sperm per mL, with normal sperm motility and morphology; his FSH and LH levels were elevated. One patient had complete normozoospermia, and the seventh patient had polyzoospermia of 340 million per mL; both of these patients had normal serum hormone levels. Only the patient with oligozoospermia reported a history of delayed testicular descent; his physical examination showed relatively soft and small testicles and a varicocele with considerable reflux. The physical andrological examinations were normal in the other 6 patients. It is very likely that the azoospermia in the 4 patients can be attributed to the radiation accident. In conclusion, it is essential to perform andrological examinations in patients who have been exposed to radiation even if there are only cutaneous injuries detectable, as a high percentage of them can show azoospermia.

The radiation accident in Georgia: clinical appearance and diagnosis of cutaneous radiation syndrome.

BACKGROUND: Eleven male Georgian soldiers were accidentally exposed to radiation by cesium 137 during their training in a military exercise camp in Lilo, Georgia between November 1996 and May 1997. OBJECTIVE: The characteristic sequelae of accidental cutaneous irradiation and available diagnostic methods are described. METHODS: Magnetic resonance imaging (MRI) of radiation ulcers was performed in all patients; thermography was performed in 2. In 7 patients ulcers and white macules were examined with high-frequency 20 MHz sonography; histologic results were obtained from all patients. RESULTS: Predominant lesions were radiation ulcers in 11 patients and white hairless macules in 7. MRI showed ulcers down to the muscles and an increase of signal intensity in the musculature in 9 cases. The corresponding muscle histology demonstrated vasculitis in 7 patients and necrosis in 2. In 2 patients, MRI signal intensity of the musculature was normal. In 3 patients, 20 MHz sonography showed dermal defects; 1 patient had cutaneous fibrosis. Thermography demonstrated hypothermic zones with extended inflammatory zones adjacent to the radiation ulcers in both patients examined. CONCLUSION: High-frequency 20 MHz sonography, MRI, and thermography are useful noninvasive methods for diagnosis of the extent of cutaneous radiation syndrome and for therapy planning.

Quantitation of herpes simplex DNA in blood during aciclovir therapy with competitive PCR ELISA.

BACKGROUND: Monitoring viral load in blood has already been introduced into clinical routine for human immunodeficiency virus and hepatitis C virus. OBJECTIVE: This study was conducted to monitor the decline of herpes simplex (HSV) viral load in the blood of a patient with gingivostomatitis herpetica prior and during acyclovir therapy. METHODS: Analysis was done by quantitative PCR ELISA using an internal quantitation standard. RESULTS: Copy numbers were 66/microl blood prior to therapy, 60 during oral medication with valaciclovir, 97 and 72 copies/microl blood during the first 2 days of intravenous acyclovir therapy, followed by a sharp decline to 8 and 9 copies on days 3 and 4. During the following days, HSV was no longer detectable. CONCLUSION: As this quantitative approach can be easily adjusted to any other PCR, it provides a reliable, easy-to-apply method for monitoring therapy, also during new antiviral clinical trials.

Detection of herpes simplex virus and varicella-zoster virus in clinical swabs: frequent inhibition of PCR as determined by internal controls.

BACKGROUND: PCR-based detection of microorganisms is widely used for diagnostic purposes. Most routine PCR applications do not control for inhibition of PCR, thus leading to false-negative results. METHODS AND RESULTS: One hundred eighteen swab samples obtained from skin and mucosa were investigated for the presence of herpes simplex virus (HSV), varicella-zoster virus (VZV), and the control gene betaglobin by internally controlled PCR with purified and unpurified DNA in parallel. With unpurified DNA, inhibition of PCR was detected in 23% of betaglobin PCRs, 25% of VZV PCRs, and 16% of HSV PCRs versus 3% each for purified DNA. Approximately 20% of the samples with positive results for HSV or VZV had negative or inhibited results using unpurified DNA. CONCLUSION: These results indicate that PCR from clinical swab specimens should be performed exclusively with internal controls because the positive control alone cannot exclude PCR inhibition in individual samples. Purification of DNA will decrease, but not exclude, PCR inhibition.

Chronic sclerodermic graft-versus-host disease refractory to immunosuppressive treatment responds to UVA1 phototherapy.

Graft-versus-host disease is a frequent complication of allogenic bone marrow transplantation. Approximately 10% of patients suffering from chronic graft-versus-host disease develop sclerodermic graft-versus-host disease of the skin, which often does not respond to conventional immunosuppressive therapy. An alternative to immunosuppressive treatment is photochemotherapy. We describe a patient with chronic sclerodermic graft-versus-host disease who did not respond to a combination therapy of cyclosporine and prednisone and later mycophenolate mofetil plus prednisone. A combination therapy of mycophenolate mofetil (2 g/day) and low-dose UVA(1) therapy (single dose, 20 J/cm(2), 4 times per week over 6 weeks) resulted in striking clinical improvement of sclerodermic graft-versus-host disease.

Interferon gamma in survivors of the Chernobyl power plant accident: new therapeutic option for radiation-induced fibrosis.

BACKGROUND: One of the remarkable clinical consequences of the Chernobyl accident was skin involvement, leading to extensive cutaneous fibrosis. Apart from surgery, no established treatment is available. METHODS: A group of survivors, working in or present at the accident site on April 26, 1986, and a few days thereafter, were examined, treated, and followed-up in 6-month intervals from September 1991 to November 1995. Eight individuals were identified as suffering from excessive cutaneous fibrosis. Skin thickness was measured with high-frequency (20 MHz) ultrasound in a clinically well-defined target skin lesion, in addition to histologic confirmation of radiation fibrosis. Interferon gamma was scheduled for all patients on a low-dose regimen (3 x 50 microg/week s.c.). In 2 patients, interferon was discontinued after the first injection, due to withdrawal of consent. In 6 patients, interferon was continued for 30 months, with 1 injection weekly for a further 6 months. Treatment was discontinued in November 1994. Four patients in the treated group and 1 of the 2 patients treated only once ("untreated patients") were reexamined 1 year later. RESULTS: In all individuals treated for 36 months, a significant (p < 0.005) reduction of radiation fibrosis could be determined, in contrast to a significant (p < 0.005) increase in the 2 untreated patients. Follow-up 1 year after discontinuation of the interferon treatment demonstrated significant (p < 0.005) recurrence of fibrosis. CONCLUSION: Low-dose interferon appears to be a safe and effective treatment of cutaneous radiation fibrosis following accidental exposure to high doses of ionizing radiation. Long-term supportive therapy may be required.