Metastatic melanoma mimicking solitary fibrous tumor: report of two cases

Malignant melanomas are known for their remarkable morphological variation and aberrant immunophenotype with loss of lineage-specific markers, especially in recurrences and metastases. Hot spot mutations in BRAF, NRAS, GNAQ, and GNA11 and mutations in KIT are oncogenic events in melanomas. Therefore, genotyping can be a useful ancillary diagnostic tool. We present one case each of recurrent and metastatic melanoma, both showing histological and immunohistochemical features of solitary fibrous tumor (SFT). Mutational analysis detected BRAF and NRAS mutations in the primary and secondary lesions, respectively. This result confirmed the diagnosis of recurrent/metastastic melanoma.     

Macrophage migration inhibitory factor may contribute to vasculopathy in systemic sclerosis

Increasing evidence supports the concept of macrophage migration inhibitory factor (MIF) as a central proinflammatory cytokine in autoimmune diseases. To further evaluate its role in systemic sclerosis (SSc), serum levels of MIF were determined by enzyme-linked immunoassay, and correlations to clinical manifestations were analyzed in 43 patients. MIF levels were significantly increased in patients (median, 18.8; range, <0.015-189 ng/ml) in comparison to healthy controls (n = 43, 8.0, <0.015-36.5 ng/ml; P < 0.0005). MIF values were higher in diffuse than in limited cutaneous SSc (P < 0.005). Patients with pulmonary hypertension and recurrent digital ulcers showed higher MIF levels than patients without these manifestations (P < 0.005). This association was also observed in limited cutaneous SSc. Sequential studies revealed decreased MIF levels after initiation of immunosuppressive therapy. MIF levels were not significantly different in patients with and without macrovascular disease of the peripheral arteries. The results suggest that MIF might contribute to inflammation and vasculopathy in SSc.     

The transforming growth factor-beta1 gene polymorphism (G915C) is not associated with systemic lupus erythematosus

Lymphocyte production of transforming growth factor (TGF)-beta1 is decreased in systemic lupus erythematosus (SLE). The lack of this immunoregulatory cytokine may contribute to the characteristic T cell disregulation and aberrant B cell stimulation in SLE patients. The less common C allele of the TGFB1 polymorphism (G915C) is associated with a lower TGF-beta1 production capacity. We performed a population-based case-control study to analyse the impact of this polymorphism on disease susceptibility, on clinical SLE manifestations and autoantibody production. A total of 203 German Caucasian SLE patients (fulfilling the 1982 ACR disease duration 11.5 +/- 7.0 years) and 158 ethnically, age- and sex-matched healthy controls were genotyped with a mutagenically separated polymerase chain reaction. There were no significant differences in the genotype distribution and allele frequencies between patients (915 C = 0.08) and healthy controls (915 C = 0.10). Comparing subgroups of patients, we found no association of major disease manifestations or specific autoantibodies with TGFB1 genotypes or alleles. The TGFB1 polymorphism (G915C) neither significantly contributes to the disease susceptibility, nor predisposes to clinical and immunological manifestations typical of SLE. Further studies are needed to corroborate the pathogenic role of TGF-beta1 in SLE patients and to identify the precise genetic elements controlling its production.     

Cat scratch disease (bartonellosis) mimicking an SLE flare.

Only recently Bartonella species have been recognized as important human pathogens. Cat scratch disease (CSD), caused by infection with Bartonella henselae, shows a steady increase in the number of cases throughout the world. We report a case of an 18-year-old woman with systemic lupus erythematosus (SLE) who presented with ongoing fever, arthralgias and loss of weight which did not respond to increasing doses of corticosteroids. After exclusion of common infections a photograph of her cat in combination with scratch marks on her arms finally led to the suspicion of CSD. This tentative diagnosis was confirmed serologically. Under clarithromycin treatment the patient rapidly responded and her temperature dropped within 2 days.     

Chirurgische Therapieergebnisse beim asymptomatischen primären Hyperparathyreoidismus

Zusammenfassung. Die Behandlung des symptomatischen prim?ren Hyperparathyreoidismus ist die Operation. Ein breiter Einsatz labortechnischer Untersuchungen hat zu einer geh?uften Diagnose eines asymptomatischen prim?ren Hyperparathyreoidismus (pHPT) geführt. Bei diesen Patienten wird die Indikation zum operativen Vorgehen kontrovers diskutiert. Ziel der Studie war eine Morbidit?tsanalyse sowie die potentielle Identifikation prognostischer Parameter in der Gruppe der asymptomatischen Patienten. Im prospektiv erfa?ten HPT-Krankengut unserer Klinik wurden zwischen Januar 1988 und August 1995 243 Patienten an einem pHPT operiert. 76 Patienten erfüllten die Kriterien eines asymptomatischen pHPT. 75 % der Patienten waren weiblich, das Durchschnittsalter lag bei 62 Jahren. Die fakultativ eingesetzte cervicale Sonographie wurde bei 87 % der Patienten zur Lokalisationsdiagnostik durchgeführt. Vor cervicalen Reeingriffen erfolgte eine selektive Halsvenenkatheterisierung zur stufenweisen Parathormonbestimmung. Eine univariate statistische Analyse zur Identifikation von Risikofaktoren für postoperative Komplikationen wurde erstellt. Chirurgisch wurden 68 singul?re Epithelk?rperchenadenome, 3 Doppeladenome und eine prim?re Hyperplasie erfolgreich therapiert (94,7 %). Vier Patienten verblieben hypercalci?misch, die Persistenzrate betrug somit 5,2 %. Eine korrekte Lokalisationsdiagnostik fand sich bei 58 % der cervicalen Sonographien und bei 77 % der selektiven Venenkatheteruntersuchungen. Postoperativ waren eine permanente Recurrensparese und zwei Nachblutungen, welche durch einen Reeingriff kontrolliert werden konnten, zu verzeichnen. 18 Patienten wiesen einen passageren Hypoparathyreoidismus auf, bei einem Patienten erfolgte auch nach zwei Jahren noch eine Medikation zum Ausgleich einer Hypocalci?mie. Eine postoperative Letalit?t trat nicht auf. Die Analyse potentieller Risikofaktoren wies nur für den cervicalen Reeingriff nach vorausgegangener Epithelk?rperchenrevision ein erh?htes operatives Risiko nach (p = 0,02). Die Operation beim asymptomatischen HPT ist von einer geringen Morbidit?t begleitet. Cervicale Reeingriffe bedürfen einer kritischen Indikation bei nachweisbar erh?hter Morbidit?t, abgesehen von dieser kleinen Gruppe aber sollten alle Patienten mit einem asymptomatischen pHPT für eine Operation evaluiert werden.      

P03Type‐I and ‐IV hypersensitivity to platinum salts

A 28‐year‐old female analytical chemist visited our patch test clinic with initially complaints of severe hand dermatitis. Later on she developed rhinitis, bronchial asthma and tightness of the chest. The complaints seemed work related: her condition improved during holidays and on sick leaves. She worked in a laboratory with several platinum salts and used different kinds of gloves (latex, nitril, etc.).
Methods:  Patch tests were performed with the European Standard series and prick tests with common inhalant allergens. Patch‐, prick‐ and open patch tests were carried out with various aqueous dilutions of platinum chloride (PtCl2).
Results:  Patch tests with 0.01–2% PtCl2 were positive on day 2, 3 and 6, and at 0.001% a follicular reaction was found. The prick‐test was already positive at the lowest concentration tested (0.001%). The open patch test, carried out retro‐auricular, showed a positive reaction at 1 and 2% PtCl2 after 20 min. Controls in healthy volunteers (n = 5) were all negative.
Discussion:  It is well known that platinum salts can cause type‐I hypersensitivity reactions like allergic rhinitis, conjunctivitis, bronchial asthma and urticaria, also referred to as platinosis. Contact dermatitis to platinum salts, however, is very rare. In our patch test clinic, 78 patients were tested between 1987 and 2001 with PtCl2 2%. Only 2 women showed a positive patch test for PtCl2. The patient presented here, stopped working with platinum salts and recovered from all complaints. We interpret our case as occupational type‐I and type‐IV hypersensitivity to platinum salts with mucosal and dermal manifestations.     

Double-blind randomized Phase I study comparing rdESAT-6 to tuberculin as skin test reagent in the diagnosis of tuberculosis infection

Limited specificity of the tuberculin skin test incited the development of in vitro assays based on Mycobacterium tuberculosis-specific antigens such as ESAT-6 that are lacking in Bacillus Calmette Guérin (BCG). In animal studies, intradermal ESAT-6 was safe and induced specific skin test responses. The aim of the study was to assess the safety of intradermal recombinant dimer ESAT-6 (rdESAT-6) compared with tuberculin and to determine the human dose. The study design was a double-blind Phase I study with intra-subject randomization to the left and right forearm, comparing 2 Tuberculin Units (TU) intradermal tuberculin (RT23) with 0.01, 0.1, 1 or 10 microg rdESAT-6 in groups of five healthy controls or treated tuberculosis (TB) patients. The risk of sensitization after skin testing was assessed in healthy volunteers. All doses were tolerated well by healthy volunteers and responses to rdESAT-6 were limited to transient redness after 24 h only at the highest dose. No sensitization was observed. Because 1 microg rdESAT-6 induced large responses with local side effects in some TB patients, the 10 microg dose of rdESAT-6 was not tested. Mean responses to 0.01, 0.1 and 1 microg rdESAT-6 measured 14.0, 19.8 and 38.8 mm of redness, respectively, and 7.0, 13.4 and 14.6 mm of induration. The response to tuberculin was similar to the responses to 0.1 microg rdESAT-6. Mild local side effects due to tuberculin and rdESAT-6 were observed in 8/15, respectively, 6/15 patients, more pronounced at the highest rdESAT-6 dose. In conclusion, this pilot Phase I study of safety, feasibility and dose finding of intradermal rdESAT-6 provides proof of principle of a specific skin test for human use. No serious adverse events were observed but the study was not sufficiently powered to demonstrate complete safety. Intradermal rdESAT-6 did not seem to sensitize healthy volunteers. In treated TB patients, responses to rdESAT-6 were optimal at 0.1 microg. Further studies are needed to evaluate sensitization after repeated doses and to study the effect of additional CFP-10 on the sensitivity of a TB-specific skin test.