["Die grosse Barb" in the museum of the University of Marburg. An early documentation of acromegaly]. / Die grosse Barb im Marburger Universitätsmuseum. Eine frühe Dokumentation der Akromegalie.

The university museum for cultural history in the castle of Marburg has a portrait "Die grosse Barb", which represents a women suffering from acromegaly. She shows the typical pathologic alterations: thickening of the skin folds, thickening of the lips and the eyelids, growth of bones and cartilages, lengthening of the nose, enlargement of the ears, protrusion of the zygoma, mandible and the chin. Acromegaly is a consequence of enhanced secretion of growth hormone, which occurs also as a symptom of several syndromes, such as multiple endocrine neoplasia type 1, McCune-Albright-syndrome, and NAME syndrome (Carney complex type I). The most remarkable symptom of acromegaly is the gigantism. This occurs also in androgen-deficient states, such as the Klinefelter syndrome and some more genetic syndromes, of which the Simpson-Golabi-Behmel syndrome, the Sotos syndrome, the Marfan syndrome, the homocystinuria, and the fragile X-syndrome may be mentioned. Nothing is known on the further fate of the patient shown in the portrait. It is also unknown, whether she owes her position as a chambermaid to her gigantism, for it was a common use in courts to have people with abnormal body shapes in attendance.

Treatment of psoriasis and psoriatic arthritis with interferon gamma.

In a placebo-controlled double-blind randomized study, 24 patients with psoriatic arthritis were given 28 d of treatment, and in an open study, 56 patients were treated for 9 months. We treated patients with 100 micrograms IFN gamma per subcutaneous injections, which were given daily for the first 2 weeks and then 3 times per week. The principal criterion for evaluation of therapeutic success on arthritis was improvement of the Ritchie joint pain index by at least 25% in the double-blind and 30% in the long-term study. In the double-blind study, the interferon arm was superior to the placebo arm with a statistically significant, one-side error probability of less than 5% in the chi-square test. In the long-term study, IFN gamma caused an improvement in a portion of patients in the first 3 months of therapy. No further improvement was observed after the third month, and patients classified as responders in the first months showed a deterioration of the disease by continuing treatment. The humoral inflammatory parameters did not normalize during therapy. Regression of the skin manifestations could not be observed. IFN gamma is evidently capable of inducing a psoriasis on the injection site. Investigations of IFN gamma serum levels, IFN antibodies, 2'-5' A synthetase levels in serum, and mononuclear blood cells and NK cell activity under long-term therapy showed no explanation for the loss of efficacy after 3 months treatment.

Examination of regional lymph nodes by sentinel node biopsy and molecular analysis provides new staging facilities in primary cutaneous melanoma.

Histopathologic parameters of the primary tumor, such as Breslow's tumor thickness and Clark's level of invasion are the current basis for prognostic classifications of primary cutaneous melanoma. Once patients develop regional node metastasis, histopathologic features of the primary melanoma no longer contribute significantly to survival prediction. In this tumor stage, the extent of lymph node involvement is the main prognostic factor. This study addresses the question whether application of a highly sensitive molecular biology assay for detection of submicroscopic melanoma cells in sentinel lymph nodes may be suitable to improve melanoma staging. One hundred and sixteen patients with primary cutaneous melanoma with a total of 214 sentinel lymph nodes were enrolled. Sentinel lymph nodes were analyzed by histopathology including immunohistochemistry and by reverse transcription-polymerase chain reaction for tyrosinase. Patients were examined for tumor recurrences during a follow-up period of 19 mo (median). Disease-free survival probabilities were calculated and independent prognostic factors were determined by multivariate analysis. Using histopathology, micrometastatic nodal involvement was detected in 15 patients (13%). Of the 101 patients with histopathologically negative sentinel lymph nodes, 36 were reclassified by positive tyrosinase reverse transcription-polymerase chain reaction and 65 patients were still negative by reverse transcription-polymerase chain reaction. Recurrences were observed in 23 (20%) of 116 patients. These tumor recurrences were demonstrated in 10 patients (67%) with histopathologically positive sentinel lymph nodes, in nine patients (25%) with submicroscopic tumor cells detected by reverse transcription-polymerase chain reaction, and in four patients (6%) negative by both methods. The differences in recurrence rates were statistically significant (p = 0.01). In a multivariate analysis, histopathologic and reverse transcription-polymerase chain reaction status of the sentinel lymph node were demonstrated to be the only significant prognostic factors for predicting disease-free survival. Tyrosinase reverse transcription-polymerase chain reaction for the detection of minimal residual melanoma in sentinel lymph nodes is a powerful tool to determine patients who are at increased risk for subsequent metastasis. Moreover, a group of patients with high tumor thickness was identified by negative reverse transcription-polymerase chain reaction to be at low risk for recurrent disease. These data may have an impact on future tumor classifications of primary cutaneous melanoma.

Patterns of local horizontal spread of melanomas: consequences for surgery and histopathologic investigation.

Understanding local spreading patterns of melanomas is a precondition for the localized surgical treatment and histopathologic investigation. We used hematoxylin and eosin-stained paraffin sections for a two-phase, cellular and microscopic study of patterns of lateral spread in superficial spreading melanomas (SSMs), nodular melanomas (NMs), lentigo maligna melanomas (LMMs), and acral lentiginous melanomas (ALMs). Complete histologic examination of vertical excisional margins was carried out with paraffin sections 5 mm beyond the clinical tumor border of 1395 SSMs, 376 NMs, 179 LMMs, 46 ALMs, and 37 acrally located SSMs or NMs. Further sections of embedded material were analyzed when tumor-positive margins were found. In case of continuous tumor spread, reoperations were continued until the tissue was free of tumor cells. In case of noncontinuity, a final excision was made to a minimum safety margin of 10 to 20 mm. Concentrically consecutive, 5-microm thick hematoxylin and eosin-stained sections were taken from the outside of a 10-mm safety margin inward to the clinical borders of 34 SSMs, five NMs, 10 LMMs, and five ALMs. Noncontinuous subclinical spread was found in all SSMs and NMs in the form of few isolated cell nests at the epidermis-dermis junction. Ninety-two percent of these were located within 6 mm of the central tumor. All LMMs and ALMs showed a clearly demonstrable, uninterrupted spread into the periphery at the epidermis-dermis junction, too, usually in groups of outgrowths. The probability of finding these outgrowths 5 mm beyond the clinical tumor border was 54% in LMM and ALM. Complete histologic examination of vertical excisional margins (micrographic surgery) is therefore the therapy of choice only for LMM and ALM and is inefficient for SSM and NM.

Detection of melanoma micrometastasis in sentinel nodes by reverse transcription-polymerase chain reaction correlates with tumor thickness and is predictive of micrometastatic disease in the lymph node basin.

The sentinel node has been reported to be representative for the presence or absence of metastatic melanoma in the draining lymph node basin. In this study, for the first time sentinel nodes and adjoining nonsentinel nodes were analyzed for micrometastatic disease using tyrosinase reverse transcription-polymerase chain reaction (RT-PCR) in comparison with standard immunohistochemistry. Successful identification of the sentinel nodes using a gamma probe-guided surgery was achieved in 73 (92%) of 79 patients with cutaneous stage I and II melanoma (tumor thickness > or =0.75 mm). A total of 794 regional lymph nodes, 148 sentinel nodes, and 646 adjoining nonsentinel nodes were evaluated. Tyrosinase RT-PCR was shown to increase the sensitivity for melanoma cell detection in sentinel nodes significantly (49% positivity) as compared with immunohistochemistry using antibodies against HMB-45 antigen and S-100 protein (18% positivity). Examination of sentinel nodes was highly predictive in determining the presence of regional lymph node micrometastasis by immunohistochemistry (99%) and RT-PCR (89%). Interestingly, detection of nodal micrometastasis by RT-PCR showed a strong positive correlation with tumor thickness of primary cutaneous melanoma. These results suggest the clinical significance and emphasize the importance of tyrosinase RT-PCR for detection of melanoma micrometastasis in sentinel nodes.

Chemotactic activity of substances derived from antibody-loaded tumor cells on granulocytes.

Chemotactic activity of granulocytes attracted by tumor cells loaded either with anti-ganglioside monoclonal antibodies (mAb) or with antibody-glucose oxidase conjugates (mAb-GO) was investigated. The melanoma cell line SK-Mel-28 which expresses the ganglioside GD3 at high density as well as the neuroectodermal cell line SK-N-LO which expresses GD2 were used for the experiments. In the presence of 50% human AB-serum, antibody-loaded tumor cells induced chemotactic activity on granulocytes, probably due to the generation of C3a/C5a which could be detected in serum incubated with anti-GD3 loaded SK-Mel-28 cells. Both compounds could also be detected in vivo in the plasma of patients suffering from neuroblastoma during therapy with anti-GD2 antibodies. In another set of experiments mAb-GO conjugates generating high amounts of H2O2 in the presence of glucose were bound to these tumor cells. A significant lipid peroxidation could be observed in the simultaneous presence of iron and ascorbate. The lipid peroxidation products were measured as thiobarbituric acid-reactive substances (TBARS) and were also shown to induce chemotactic effects on granulocytes.

Microstaging of squamous cell carcinomas.

The clinical classification of squamous cell carcinoma, which was established primarily by the International Union Against Cancer (UICC), does not permit optimal estimation of expected metastasis. The authors' results indicate that metastasis can be more accurately estimated on the basis of invasion depth, histopathologic grading, and especially tumor thickness. One essential advantage of these criteria is that they can be established by a histopathologist. It is interesting to note that in the authors' collective no carcinoma less than 2 mm thick metastasized, that is, a relatively high percentage of carcinomas (48%) can be graded as no-risk carcinomas. The risk of metastasis for undifferentiated carcinomas greater than 6 mm thick that have infiltrated the musculature, the perichondrium, or the periosteum, however, is quite high. Tumors between 2 and 6 mm thick with moderate differentiation and a depth of invasion that does not extend beyond the subcutis can be classified as low-risk carcinomas.

Anaphylactic reaction to bovine serum albumin after embryo transfer.

OBJECTIVE: To increase the awareness of bovine serum albumin (BSA) sensitivity as a potentially lethal complication during ET. DESIGN: Case report. SETTING: Routine ET in university hospital. PATIENT(S): A 26-year-old woman who was undergoing her first ET. INTERVENTION(S): ET with BSA containing standard fluid medium. MAIN OUTCOME MEASURE(S): Specific immunoglobulin (Ig) E antibodies and skin tests. RESULT(S): The patient demonstrated increased levels of specific IgE antibodies to BSA and a clearly positive scratch test for BSA. CONCLUSION(S): Anaphylactic reactions to BSA can occur during ET. The risk can be reduced substantially if a detailed medical history is obtained.

Psoriasis induced at the injection site of recombinant interferon gamma. Results of immunohistologic investigations.

Recombinant human interferon gamma used for treatment of psoriatic arthritis was found to induce expression of HLA-DR, but not HLA-DP or HLA-DQ, on keratinocytes at the site of injection. Some patients showed an improvement of their joint symptoms, but the cutaneous manifestations remained unaffected. In 10 of 42 patients, punctiform psoriatic foci could be induced at the site of injection of interferon gamma. For this presentation, we selected a female patient with psoriatic arthropathy and type II diabetes mellitus in whom psoriasis was induced at the site of application of interferon gamma, but not after subcutaneous injection of insulin or placebo. We conclude that interferon gamma is an important lymphokine in the development of psoriasis.

Dermatoscopy turns histopathologist's attention to the suspicious area in melanocytic lesions.

BACKGROUND: Histopathologically, the diagnosis of nevus-associated melanoma or melanoma close to a common nevus can be missed if the specimen is cut in a nonrepresentative area or if the section shows only the associated common nevus. OBJECTIVE: To find out whether dermatoscopy of suspicious areas within a nevus can improve the histological diagnosis of malignant melanocytic lesions of the skin. MATERIALS: The study was based on dermatoscopic images of more than 2000 benign and 115 malignant pigmented lesions and a collection of corresponding histopathologic slides. METHODS: The dermatoscopic images and the corresponding histopathologic diagnoses were compared. In case of differences, the histopathologic findings were reevaluated and compared with the dermatoscopic findings. RESULTS: Three cases were identified in which melanoma could have been histopathologically missed as a result of improper sectioning. After the dermatoscopic findings were evaluated, the specimens were reembedded and further sections were obtained. Finally, nevus-associated melanoma or melanoma close to a common nevus was diagnosed. CONCLUSIONS: Specific dermatoscopic patterns of malignancy can be found in highly suspicious areas, eg, broadened networks, radial streaming, pseudopods, or dots located at the periphery. The dermatoscopic-histopathologic correlation can improve the diagnosis of melanoma. Therefore, the clinician should point to the most suspicious area with a drawing or image, and the suspected diagnosis of melanoma and the history of the lesion should be also mentioned.

Positron emission tomography and ultrasonography. A comparative retrospective study assessing the diagnostic validity in lymph node metastases of malignant melanoma.

BACKGROUND AND DESIGN: A retrospective study involving 20 patients with melanoma with clinically suspicious lymph nodes was conducted to compare the diagnostic validity of fludeoxyglucose F 18 positron emission tomography (PET) and real-time ultrasonography in lymph node metastases of malignant melanoma. RESULTS: A total of 83 lymph nodes were assessed with ultrasonography and PET. Imaging results were confirmed by histologic studies or close follow-up ultrasonographic examinations. Positron emission tomography revealed a sensitivity of 74% and a specificity of 93%. Both investigative methods show comparative sensitivity and specificity. CONCLUSIONS: Ultrasonography is much easier to perform, less time-consuming, and less expensive than PET and it is nonhazardous; therefore, it is ideal for follow-up procedures. Since in routine staging procedures, only sites of expected lymph node involvement are examined, there is a risk of metastases being missed in cases of atypical drainage patterns. Fludeoxyglucose F 18 PET can image proliferating tumors in multiple organ systems and lymph node sites in one session, making it suitable for screening in primary staging procedures and for monitoring response to therapy. Since it is based on metabolic changes, there is good differentiation between scar and tumor tissue. Major disadvantages are restricted access to investigation centers, high imaging costs, and limited anatomical location of metastatic lesions. We conclude that PET does not offer significant advantages in the diagnosis of lymph node metastases compared with ultrasonography.

Anti-proliferative activity of natural interferon-alpha, isotretinoin and their combination varies in different human melanoma cell lines.

Natural interferon alpha (nIFN-alpha) isotretinoin and their combination were tested for their capacity to modulate the proliferation of different human melanoma cell lines. Modulation of cell growth was measured using the MTT-assay. Isotretinoin and nIFN-alpha as single agents inhibited the proliferation in a dose dependent manner in the three cell lines: SK-Mel-30, SK-Mel-28 and MaRi. The combination of isotretinoin and nIFN-alpha led to a marked enhancement of the antiproliferative effect compared with either nIFN-alpha or isotretinoin alone in SK-Mel-30 cells. In contrast, there were no additive effects on growth inhibition of melanoma cell lines SK-Mel-28 and MaRi when nIFN-alpha and isotretinoin was combined. In one melanoma cell line (MaRi) proliferation was actually enhanced by isotretinoin in combination with nIFN-alpha. These results demonstrate the heterogeneous response of human melanoma cell lines to noncytotoxic concentrations of isotretinoin and nIFN-alpha alone and in combination.

Activation of cellular cytotoxicity and complement-mediated lysis of melanoma and neuroblastoma cells in vitro by murine antiganglioside antibodies MB 3.6 and 14.G2a.

Mouse monoclonal antibodies against tumour-associated gangliosides GD2 (14.G2a) and GD3 (MB 3.6) were tested to mediate antibody-dependent cellular cytotoxicity (ADCC) with various effector cells or complement-dependent cytolysis (CDC). We also evaluated the immunomodulating potential of interferons in combination with cellular cytotoxicity. Using effector:target (E/T) ratios of 40:1, ADCC with effector cells such as granulocytes or mononuclear blood cells was not detectable against melanoma cell lines GR, SK-MEL-28 and G-361 which preferentially express GD3 and bind antibody MB 3.6. Neuroblastoma cell line SK-N-LO, which was used for comparative purposes, mainly expressed GD2 and the tumour cells were killed effectively after labelling with antibody 14.G2a. Granulocytes did not show significant killing of melanoma cells by ADCC, but neuroblastoma cells were killed very efficiently. Peripheral blood mononuclear cells (PBMC) also failed to kill melanoma cells. Interferon-beta slightly stimulated PBMC and increased killing of neuroblastoma cells, but no additive effects with ADCC were detectable. Incubation of target cells with interferons produced no significant differences in susceptibility of the target cells to interferon-activated PBMC cytotoxicity. Despite the lack of effectiveness in mediating cellular cytotoxicity, GD3 antibody MB 3.6 showed strong complement-dependent cytolysis in the presence of human plasma. There were remarkable differences in individual activity and different susceptibility of the melanoma cell lines. We assume that CDC may have more activity against melanoma cells than cytotoxicity associated with various effector cells.

Does intensive histopathological workup by serial sectioning increase the detection of lymph node micrometastasis in patients with primary cutaneous melanoma?

Various histopathological techniques have been developed in order to improve the detection of micrometastasis in the regional lymph nodes of patients with malignant melanoma. Our standard histopathological examination of lymph nodes included haematoxylin and eosin (H & E) staining and immunohistochemistry (IH) using antibodies to HMB-45 and S-100 proteins of three paraffin sections at one level. In addition, lymph nodes were examined by molecular biological methods using tyrosinase reverse transcription-polymerase chain reaction (RT-PCR). In this study, we investigated the use of step sections and IH in lymph nodes regarded as negative by standard histopathology but positive by tyrosinase RT-PCR, suggesting the presence of tumour cells. In a series of 76 consecutive patients with stage I and II cutaneous melanoma, a total of 156 regional lymph nodes were examined by H & E staining, IH and tyrosinase RT-PCR. All lymph nodes were bisected along their long axis for separate evaluation. In 21 patients, at least one lymph node in the regional nodal basin reported as tumour-negative by standard histopathology was demonstrated to express tyrosinase (total number of nodes = 33). These 33 lymph nodes were re-examined by H & E and IH at 10 additional levels of the paraffin block. Only one lymph node from one patient had occult melanoma cells in deeper levels detected exclusively by IH. Six out of 20 patients with positive findings exclusively on tyrosinase RT-PCR developed tumour recurrences during a median follow-up of 34 months. We therefore conclude that additional step sectioning with IH does not significantly increase the detection of tumour-positive lymph nodes. Patients with melanoma cells detected exclusively by RT-PCR, however, were shown to be at increased risk for tumour recurrence.

Significance of serum protein S100 levels in screening for melanoma metastasis: does protein S100 enable early detection of melanoma recurrence?

A number of recent reports suggest serum protein S100 as a prognostic parameter in patients with metastatic melanoma. In the present study, serum protein S100 was investigated as a tumour marker for screening for melanoma metastasis in patients attending regular follow-up examinations. During the period from September 1997 to December 1998, serum protein S100 levels were measured by an immunoluminometric assay in 411 consecutive high risk melanoma patients (666 samples) and in 120 control subjects. Melanoma patients with resected primary tumours with a tumour thickness of 1.5 mm or more with resected metastasis were included in the study. Overall, 41 of the 411 patients developed metastasis during the period of observation. According to the distribution of protein S100 levels, the following different cut-off values were examined: 0.08 microg/l (95 percentile of the control group) and 0.13 microg/l (95 percentile of the group of melanoma patients without metastasis). The test efficiency for protein S100 as a diagnostic test for the detection of metastasis was highest for the cut-off value of 0.13 microg/l. In eight of the 41 patients (19.5%), elevation of protein S100 was the first sign of recurrence. Of the 41 patients with metastatic disease, 13 had elevated protein S100, giving a sensitivity of 0.32. The specificity for the detection of metastasis was 0.96. In eight of the 14 patients (57%) who developed distant metastasis, elevated S100 values were the first sign of tumour progression. In conclusion, determination of serum protein S100 levels enables earlier detection of distant metastasis in patients at high risk for metastasis. The impact on survival time needs to be investigated in follow-up studies.

Prognostic impact of the type of anaesthesia used during the excision of primary cutaneous melanoma.

The prognostic value of the type of anaesthesia used for the excision of malignant tumours has been a subject of controversy. Cell-mediated as well as humoral immune responses can be compromised after general anaesthesia, and recurrences may therefore occur more frequently. On the other hand, excision of primary tumours under local anaesthesia might also influence the prognosis unfavourably. The aim of the present study was to determine the prognostic impact of general and local anaesthesia for the primary excision of cutaneous melanoma. Follow-up data of 4329 patients on the Central Melanoma Registry of the German Dermatological Society were analysed. Cox proportional hazards analysis was performed to evaluate the independent significance of the prognostic factors, and survival probabilities were calculated for matched pairs using Kaplan-Meier estimates. Statistical analysis revealed an independent significant effect on survival for tumour thickness, ulceration, level of invasion, anatomical site and gender. General anaesthesia for primary excision of melanoma was associated with a decrease in the survival rate (relative risk 1.46, P<0.0001). This study revealed a slight but significantly increased risk of death for patients treated with general anaesthesia for the primary excision of melanoma. Therefore local anaesthesia should be preferred for the treatment of primary melanoma.

Extent and consequences of physician delay in the diagnosis of acral melanoma.

The extent and consequences of professional delay in diagnosis were analysed in 83 patients with palmoplantar and subungual melanomas treated from January 1986 to March 1997 in our department. Seventeen (52%) out of 33 subungual melanomas and 10 (20%) out of 50 palmoplantar melanomas were clinically misdiagnosed by physicians. Three palmoplantar melanomas (6%) were initially misinterpreted by pathologists. In 23 of the 27 cases (85%) the clinical misdiagnosis was made by non-dermatologists. Misdiagnosis caused a median delay of 12 months in the diagnosis of palmoplantar melanomas and 18 months in the diagnosis of subungual melanomas. Delay in diagnosis was associated with increased tumour thickness, more advanced stage at time of melanoma diagnosis and a lower estimated 5-year survival rate (15.4% versus 68.9% for palmoplantar; 68.5% versus 90.9% for subungual). Acral melanomas are frequently misdiagnosed due to their less common locations and because plantar and subungual melanomas often do not fit the 'changing mole' pattern. To Improve the patient's prognosis it is necessary to increase the physicians' skill in the diagnosis of acral melanomas. Histological examination should always be performed in acral lesions that do not heal.

Effects of 8-methoxypsoralen plus 365 nm UVA light on Candida albicans cells. An electron microscopic study.

Candida (C.) albicans cells were exposed to 8-Methoxypsoralen (8-MOP) concentrations of 1.0 microgram/ml and 10.0 micrograms/ml medium and irradiated with 365 nm light. The amount of energy emitted was 4.8 J/cm2. Two divergent types of cell damage occured concerning yeast cell cytoplasm and cell wall. Two hours after exposure cytoplasmic changes involving mitochondria, which showed irregularities in shape, blurred appearance or loss of mitochondrial cristae and outer membrane were seen. The number of vacuoles was increased. The cytoplasm showed large electron transparent areas, the cytoplasmic membrane disappeared in some areas completely. Nucleus and nuclear envelope usually remained intact in early stages. 24 h after exposure conspicuous cell wall alterations were observed in addition to cytoplasmic changes. Newly produced cell wall material formed ball-like protrusions or was adherent sickle-shaped to the cell wall. The investigations strongly suggest that the results found after 8-MOP-UVA treatment of C. albicans cells can not be interpreted in the sense of a general cytotoxic effect. Apparently it takes the form of a combination of events involving regressive and progressive alterations.

Effects of 8-methoxypsoralen plus 365 nm UVA light on Candida albicans cells. An electron microscopic study.

Candida (C) albicans cells were exposed to 8-Methoxypsoralen (8-MOP) concentrations of 1.0 microgram/ml and 10.0 microgram/ml medium and irradiated with 365 nm light. The amount of energy emitted was 4.8 J/cm2. Two divergent types of cell damage occured concerning yeast cell cytoplasm and cell wall. Two hours after exposure cytoplasmic changes involving mitochondria, which showed irregularities in shape, blurred appearance or loss of mitochondrial cristae and outer membrane were seen. The number of vacuoles was increased. The cytoplasm showed large electron transparent areas, the cytoplasmic membrane disappeared in some areas completely. Nucleus and nuclear envelope usually remained intact in early stages. 24h after exposure conspicuous cell wall alterations were observed in addition to cytoplasmic changes. Newly produced cell wall material formed ball-like protrusions or was adherent sickle-shaped to the cell wall. The investigations strongly suggest that the results found after 8-MOP-UVA treatment of C. albicans cells can not be interpreted in the sense of a general cytotoxic effect. Apparently it takes the form of a combination of events involving regressive and progressive alterations.

Fetal alcohol syndrome (FAS) in dermatology: an overview and an evaluation.

Certain skin disorders are affected by alcohol abuse. Maternal alcohol abuse during pregnancy also gives rise to a typical malformation pattern in the child with a varying degree of severity (grade I-III). The diagnosis of fetal alcohol syndrome (FAS) is based on the detailed history of the maternal alcohol consumption in combination with the clinical, morphological, intellectual and psychosocial development of the child. The behavior of the child is also of diagnostic value. The grade of severity of the FAS can be determined during the first three years of life on the basis of a scoring system. In addition to medical care and surgical treatment of associated disorders, early support for the mental development of the child is of immense importance. Furthermore, the medical, social and psychological care of the mother must be considered. In the field of dermatology, knowledge about the pathomechanism of FAS is also important for its prevention in unborn children. Women of childbearing age presenting with dermatological signs of possible alcohol abuse, should alert the dermatologist to the possible risk to the child of FAS. Familiarity with FAS and the ability to recognise its clinical features are important for the adequate treatment and support of the affected child and for the mother suffering from alcohol disease, in cooperation with other treating doctors.