[Cutaneous manifestations of sarcoidosis]. / Kutane Manifestationen bei Sarkoidose.

Skin manifestations of sarcoidosis occur in up to 30% of cases. This review summarizes and illustrates in detail the differences between specific and unspecific skin manifestations of sarcoidosis. Important differential diagnoses, such as tuberculosis, cutaneous lymphoma and syphilis have to be excluded. The indications for systemic treatment are primarily determined by the extent of organ involvement and also by the cosmetic impairment.

General anaesthesia-induced anaphylaxis: impact of allergy testing on subsequent anaesthesia.

BACKGROUND: Immunoglobulin E-mediated allergy to drugs and substances used during general anaesthesia as well as non-allergic drug hypersensitivity reactions may account for anaesthesia-induced anaphylaxis. As IgE-mediated anaphylaxis is a potentially life-threatening reaction, identification of the culprit allergen is essential to avoid anaphylaxis recurrence during subsequent general anaesthesia. OBJECTIVE: To study whether preventive recommendations derived from allergy testing after intraoperative anaphylaxis were followed in subsequent general anaesthesia. METHODS: Results of standardized allergy testing after anaesthesia-induced anaphylaxis and outcome of subsequent general anaesthesia were analysed retrospectively. RESULTS: Fifty-three of 107 patients were diagnosed with IgE-mediated allergy to a drug or substance used during general anaesthesia, and 54 patients were test negative. Twenty-eight of 29 allergy patients tolerated subsequent general anaesthesia uneventfully. One patient with cefazolin allergy suffered from anaphylaxis recurrence due to accidental reapplication of cefazolin. Twenty-two of 24 test-negative patients tolerated subsequent general anaesthesia, whereas two patients again developed anaphylaxis despite pre-medication regimens. CONCLUSION AND CLINICAL RELEVANCE: Our results confirm the practical impact of allergy testing in general anaesthesia-induced anaphylaxis. By identification of the allergen, it is possible to avoid allergic anaphylaxis during subsequent anaesthesia. In most cases, recommended pre-medication seems to prevent the recurrence of non-allergic drug hypersensitivity reactions.

Aminopenicillin-associated exanthem: lymphocyte transformation testing revisited.

BACKGROUND: The lymphocyte transformation test (LTT) has been promoted as in-vitro test for diagnosis of drug hypersensitivity. For determination of statistical LTT sensitivity, series of patients with clinically uniform reactions followed by complete drug hypersensitivity work-up are mandatory. Assessment of LTT specificity requires control patients who tolerated exposure to the drug studied. OBJECTIVE: To prospectively determine the diagnostic value of the LTT in a clinically and diagnostically well-defined series of patients. METHODS: Patients with exanthematous skin eruptions after ampicillin (AMP) intake were included in this study. After exclusion or confirmation of delayed-onset allergic AMP hypersensitivity by skin and provocation testing, two independent LTTs were performed: one standard LTT and a modified LTT with additional anti-CD3/anti-CD28 monoclonal antibody stimulation. RESULTS: By testing, delayed-onset allergic AMP hypersensitivity was diagnosed in 11 patients and definitely ruled out in 26. The standard LTT reached a diagnostic sensitivity of 54.5% while the modified LTT yielded 72.7%. However, the methodical test modification resulted in a decline of specificity from 92.3% (standard LTT) to 76.9%. CONCLUSIONS AND CLINICAL RELEVANCE: In cases of AMP-associated exanthems, the diagnostic value of the LTT compared with routine allergy testing is limited. When evaluating such exanthems, provocation testing remains the gold standard. Delayed reading of intradermal skin tests remains most useful to avoid positive provocation reactions.

[Serious complications following gluteal injection of silicone]. / Schwere Komplikationen nach glutealer Silikoninjektion.

Silicone has a broad range of medical applications and plays an important role, for example, in plastic reconstruction. The use of silicone, however, may result in unpredictable consequences for the patient. These range from swelling and erythema at the site of injection and regional lymphadenopathy to the development of disseminated granulomas distant from the administration site. We report a woman who developed extensive distally-spreading ulcerations in both buttocks several years after gluteal silicone injection. Potential systemic reactions of silicone include intrapulmonary granulomas, embolism and related pneumonitis. Moreover, an association with the development of autoimmune diseases and neoplasias has been discussed. Therapeutic options include surgically removing the silicone and topical or systemic anti-inflammatory drug therapy. However, due to the diffuse dissemination of silicone, the former is often not completely possible and for the latter empirical data are limited and follow-up studies are missing. Liquid silicone is no longer authorized in Europe or in the U.S.A. When silicone implants are used, the decision should be weighed carefully and the patient adequately counseled. In addition, follow-up care on a regular basis is mandatory for both those with implants and those who obtained injections of liquid silicone in the past.

[Uncommon cutaneous ulcerative and systemic sarcoidosis. Successful treatment with hydroxychloroquine and compression therapy]. / Seltene ulzerierende kutane und systemische Sarkoidose. Erfolgreiche Therapie mit Hydroxychloroquin und medizinischer Kompressionstherapie.

Sarcoidosis is a granulomatous multisystemic disease of unclear etiology, which can affect any organ. The cutaneous manifestations are variable, but ulcerative cutaneous sarcoidosis is very rare. One must rule out other granulomatous skin diseases, especially necrobiosis lipoidica. There is no standarized therapy; usually an interdisciplinary approach over years taking multiple side effects into consideration is needed. A 58-year-old woman with a long history of cutaneous, nodal and pulmonary sarcoidosis suddenly developed ulcerations within the disseminated skin lesions on her legs. The combination of systemic hydroxychloroquine and modern wound management lead to complete healing of the ulcers and a significant improvement in the remaining skin lesions.

Diagnostic testing in suspected fluoroquinolone hypersensitivity.

BACKGROUND: Because of their broad antibacterial activity in the gram-negative and gram-positive spectrum, high oral bioavailability, and good tissue penetration, fluoroquinolone antibiotics are widely used. Besides direct drug-related side-effects, fluoroquinolones may cause hypersensitivity reactions. OBJECTIVE: The aim of this retrospective analysis was to present the results of diagnostic testing in cases of clinically suspected fluoroquinolone-induced immediate or delayed hypersensitivity. METHODS: We studied 101 patients with a history of immediate or delayed hypersensitivity symptoms in temporal relation to treatment with a fluoroquinolone antibiotic using standardized skin testing, followed by oral challenges. Patients with anaphylaxis symptoms were further evaluated with in vitro tests. RESULTS: Fluoroquinolone hypersensitivity was excluded in 71 patients by tolerated oral challenge tests. During positive challenge tests, six patients (three out of these had positive and three had negative skin prick tests) developed anaphylaxis symptoms but the presumed IgE-mediated mechanism could not be confirmed by in vitro tests. Patch testing was constantly negative; however, in two patients a rash was induced by the challenge tests. CONCLUSION: History alone leads clearly to a considerable over-estimation of fluoroquinolone hypersensitivity. Moreover, skin or in vitro tests do not seem to be very useful in identifying hypersensitive patients. Challenge tests appear to be necessary for definitely confirming or ruling out fluoroquinolone hypersensitivity.

Superimposed linear psoriasis: differential therapeutic response of linear and nonlinear lesions.

Linear psoriasis is a very unusual clinical variation of psoriasis. Typical clinical features include early onset of erythematosquamous lesions along Blaschko's lines, ability to elicit psoriatic features, absence of pruritus and positive family history for psoriasis. Recently, the term 'superimposed linear psoriasis' was coined for cases with development of nonlinear psoriatic lesions at predilection sites in later life. We report a 19-year-old woman meeting all criteria for the diagnosis of superimposed linear psoriasis including typical histological features. Remarkably, treatment with topical steroids and dithranol cleared the psoriatic lesions on predilection sites whereas the linear lesions were resistant to topical therapy. Linear psoriatic lesions are believed to be caused by genetic alterations in early embryogenesis leading to loss of heterozygosity at a gene locus involved in the pathogenesis of psoriasis. Comparison of mosaic keratinocytes derived from linear lesions with wild-type keratinocytes from the same person may therefore allow identification of key regulatory genes.

Linear variant of chronic cutaneous lupus erythematosus: a clue for the pathogenesis of chronic cutaneous lupus erythematosus?

Lesions of chronic cutaneous lupus erythematosus usually occur in a discoid pattern as erythematous, well-defined, scaly patches affecting face and scalp. The linear variant of chronic cutaneous lupus erythematosus is an exceptional clinical variation with band-like arranged lesions along the lines of Blaschko which represent the developmental growth pattern of embryonic ectodermal cells. Therefore, this unusual clinical observation may provide additional clues for the pathogenesis of chronic cutaneous lupus erythematosus. It is intriguing to hypothesize that linear lesions of chronic cutaneous lupus erythematosus may be caused by increased susceptibility of resident skin cells due to mutations of genes in early embryogenesis.

A high school gym-induced disease.

Physical exercise may induce upper and lower airway symptoms such as rhinitis and asthma. Rhinitis symptoms are often neglected although runny nose and nasal congestion may interfere with performance of the affected individual. A detailed history regarding locality and time of symptoms is of most significance for taking the appropriate diagnostic measures and identifying, as in this case, an uncommon form of allergic rhinitis to airborne spores from moulds.

Rituximab in autoimmune bullous diseases: mixed responses and adverse effects.

BACKGROUND: Intolerably high doses of systemic corticosteroids and additional immunosuppressants may be required to control disease activity in autoimmune bullous skin diseases. New therapeutic options are needed for such patients. OBJECTIVES: To determine the efficacy and adverse effects of adjuvant rituximab. METHODS: Seven patients with refractory autoimmune blistering diseases (pemphigus vulgaris, PV, n = 4; bullous pemphigoid, BP, n = 2; mucous membrane pemphigoid, MMP, n = 1) were treated four times with rituximab at an individual dose of 375 mg m(-2) at weekly intervals. RESULTS: All lesions cleared in three patients (two PV, one BP), while they were reduced by more than 50% in three others (two PV, one BP). The concomitant immunosuppressive medication was reduced in five patients (four PV, one BP). The patient with MMP developed bilateral blindness while nasopharyngeal lesions resolved. Three patients (two BP, one PV) experienced severe adverse events including fatal pneumonia. CONCLUSIONS: Adjuvant B-cell depletion by rituximab is effective in otherwise therapy-resistant bullous autoimmune disorders but may be associated with substantial adverse effects including fatal outcomes.

Congenital brachydactyly and nail hypoplasia: clue to bone-dependent nail formation.

Congenital hyponychia and anonychia are rare malformations which may form part of syndromes such as nail-patella syndrome, ectodermal dysplasias and brachydactylies, or may occur as an isolated finding. Congenital hyponychia and anonychia are frequently accompanied by underlying skeletal abnormalities. A 20-year-old woman showed congenital bilateral hypoplasia or aplasia of the second, third and fourth toenails with corresponding phalanx dysplasia or aplasia of the affected toes. Malformations of the hands or other congenital defects were absent. The findings in this patient do not exactly fit any known entities. Our clinical observation prompted us to review the literature on congenital hyponychia/anonychia and to summarize recent advances in understanding molecular events in nail development. In conclusion, the association of nail anomalies with aplasia and/or hypoplasia of corresponding middle and/or distal phalanges supports the hypothesis of bone-dependent nail formation.

Trichorhinophalangeal syndrome type I: clinical and molecular characterization of 3 members of a family and 1 sporadic case.

BACKGROUND: Trichorhinophalangeal syndrome type I (TRPS I) is a rare autosomal dominant disorder clinically characterized by sparse and slow-growing hair, pear-shaped nose, elongated philtrum, thin upper lip, and bone deformities, in particular, cone-shaped epiphyses of the phalanges. Very recently, the responsible gene TRPS1 has been cloned on human chromosome 8q24. OBSERVATION: We describe a mother and her 2 daughters and a female patient with a sporadic case of TRPS I. In the familial case, mutation analysis showed an insertional mutation at position 2480 of the TRPS1 gene leading to a premature translational stop. Careful clinical examination showed craniofacial and radiologic features typical of TRPS I, including short stature, in all 3 affected individuals. Additionally, they presented with a receded triangular medio-occipital hairline, which has not been described in TRPS I so far. In the sporadic case, we identified a single base deletion at position 2110 of the TRPS1 gene leading to frameshift and premature translational stop at codon 766. The patient presented with the typical TRPS I phenotype but was of normal stature. CONCLUSIONS: The TRPS I is characterized by variable clinical expression of the triad of hair, craniofacial, and skeletal abnormalities. New genetic approaches, including mutation analysis, now allow identification of carriers of the TRPS1 gene mutations.

[Successful treatment of angiosarcoma with liposomal-encapsulated doxorubicin]. / Erfolgreiche Therapie eines Angiosarkoms mit liposomal verkapseltem Doxorubizin.

Cutaneous angiosarcoma is a rare tumor of endothelial origin, often difficult to diagnose and with an unfavorable prognosis. A 85-year-old woman presented with an extensive angiosarcoma involving her right leg. The tumor was not clinically typical but the diagnosis was confirmed histologically. Because of her age and the extent of the tumor, we elected to treat primarily with cobalt-60 irradiation. The tumor unfortunately progressed during radiation therapy, so we decided to begin palliative chemotherapy with liposome-encapsulated doxorubicin. The patient received six cycles of doxorubicin (Caelyx, 15 mg/m(2) i.v. in four-week intervals) which was well-tolerated and led to complete regression of angiosarcoma which has lasted for 6 months. Chemotherapy with liposome-encapsulated doxorubicin may represent a well-tolerable therapeutic option in cases where surgery and irradiation are not possible or fail. Further studies are necessary to prove the efficacy of doxorubicin therapy in angiosarcoma.

Ras-independent activation of the Raf/MEK/ERK pathway upon calcium-induced differentiation of keratinocytes.

MAPKs are crucially involved in the regulation of growth and differentiation of a variety of cells. To elucidate the role of MAPKs in keratinocyte differentiation, activation of ERK, JNK, and p38 in response to stimulation with extracellular calcium was analyzed. We provide evidence that calcium-induced differentiation of keratinocytes is associated with rapid and transient activation of the Raf/MEK/ERK pathway. Stimulation of keratinocytes with extracellular calcium resulted in activation of Raf isozymes and their downstream effector ERK within 10-15 min, but did not increase JNK or p38 activity. Calcium-induced ERK activation differed in kinetics from mitogenic ERK activation by epidermal growth factor and could be modulated by alterations of intracellular calcium levels. Interestingly, calcium stimulation led to down-regulation of Ras activity at the same time that ERK activation was initiated. Expression of a dominant-negative mutant of Ras also did not significantly impair calcium-induced ERK activation, indicating that calcium-mediated ERK activation does not require active Ras. Despite the transient nature of ERK activation, calcium-induced expression of the cyclin-dependent kinase inhibitor p21/Cip1 and the differentiation marker involucrin was sensitive to MEK inhibition, which suggests a role for the Raf/MEK/ERK pathway in early stages of keratinocyte differentiation.