Integrating the Health-care Enterprise Pathology and Laboratory Medicine Guideline for Digital Pathology Interoperability.

Integrating the health-care enterprise (IHE) is an international initiative to promote the use of standards to achieve interoperability among health information technology systems. The Pathology and Laboratory Medicine domain within IHE has brought together subject matter experts, electronic health record vendors, and digital imaging vendors, to initiate development of a series of digital pathology interoperability guidelines, called "integration profiles" within IHE. This effort begins with documentation of common use cases, followed by identification of available data and technology standards best utilized to achieve those use cases. An integration profile that describes the information flow and technology interactions is then published for trial use. Real world testing occurs in "connectathon" events, in which multiple vendors attempt to connect their products following the interoperability guidance parameters set forth in the profile. This paper describes the overarching set of integration profiles, one of which has been published, to support key digital pathology use cases.

Pegylated liposomal-encapsulated doxorubicin in cutaneous composite lymphoma: A case report.

BACKGROUND: Cutaneous composite lymphomas are very rare. Their treatment depends upon the different contributing lymphoma entities. Peripheral T-cell lymphoma, not otherwise specified, (PTCL-NOS) represents an aggressive lymphoma subtype. Follicular cutaneous B-cell lymphoma (FCBCL) runs an indolent course. Treatment with pegylated liposomal encapsulated doxorubicin (PLE-DOXO) has yet not been reported in this entity. CASE PRESENTATION: A 73-year-old male patient presented with 3 rapidly growing, painful nodules on his left leg. He was diagnosed as composite cutaneous lymphoma consisting of PTCL-NOS and FCBCL. All lesions had been surgically removed. Staging was unremarkable. After 4 months a relapse occurred with involvement of inguinal lymph nodes and systemic treatment with PEL-DOXO 20 mg/ m every 3 weeks was initiated. After 6 cycles PLE-DOXO, which were well tolerated without grade 3 or 4 toxicities, a mixed response was obtained with complete remission of cutaneous lesions.Lymph nodes were treated by radiotherapy. A second relapse occurred after 8 months and various polychemotherapy regimens were applied without remission. The overall survival was 28 months. CONCLUSION: PEL-DOXO is a possible initial systemic treatment in case of PCTL-NOS. Whether polychemotherapy offers an advantage for survival remains questionable but further investigations are needed.

The Diagnosis and Treatment of Nail Disorders.

BACKGROUND: Nail disorders can arise at any age. About half of all nail disorders are of infectious origin, 15% are due to inflammatory or metabolic conditions, and 5% are due to malignancies and pigment disturbances. The differential diagnosis of nail disorders is often an area of uncertainty. METHODS: This review is based on publications and guidelines retrieved by a selective search in PubMed, including Cochrane reviews, meta-analyses, and AWMF guidelines. RESULTS: Nail disorders are a common reason for derma - tologic consultation. They are assessed by clinical inspection, dermatoscopy, diagnostic imaging, microbiological (including mycological) testing, and histopathological examination. Some 10% of the overall population suffers from onychomycosis, with a point prevalence of around 15%. Bacterial infections of the nails are rarer than fungal colonization. High-risk groups for nail disorders include diabetics, dialysis patients, transplant recipients, and cancer patients. Malignant tumors of the nails are often not correctly diagnosed at first. For subungual melanoma, the mean time from the initial symptom to the correct diagnosis is approximately 2 years; this delay is partly responsible for the low 10-year survival rate of only 43%. CONCLUSION: Evaluation of the nail organ is an important diagnostic instrument. Aside from onychomycosis, which is a common nail disorder, important differential diagnoses such as malignant diseases, drug side effects, and bacterial infections must be considered.

Atypical fibroxanthoma: a series of 56 tumors and an unexplained uneven distribution of cases in southeast Germany.

BACKGROUND: Atypical fibroxanthoma is a rare mesenchymal tumor of the head and neck region. METHODS: We analyzed the files of 3 large dermatology hospitals from the years 2001 to 2013 in southeast Germany. RESULTS: We identified 53 patients (56 tumors) with a male predominance. The mean age was 78.0 years ± 8.3 years. Mohs surgery was performed in all cases resulting in complete remission in 45 patients. Five patients had a relapse within 2 years, and 4 developed metastases. None of the tumors with a safety margin of ≥2 cm relapsed. The majority of cases were found in the Dresden region. CONCLUSION: Atypical fibroxanthoma demonstrates an uneven geographic distribution in southeast Germany that demands further investigations. Mohs surgery with ≥2 cm safety margins is the treatment of choice. A regular follow-up is recommended.

A reference model based interface terminology for generic observations in Anatomic Pathology Structured Reports.

BACKGROUND: Current terminology systems for structured reporting in pathology are more or less focused on tumor pathology. They have not been compiled in a systematic approach, therefore they gather terms of very different granularity. Generic models for terminology development could help in establishing reference terminologies for all fields of anatomic pathology. METHODS: For each element template of PathLex its possible generic nature and its value set was analyzed, looking for the uniqueness or multiplicity of the values in the value sets. RESULTS: The 488 PathLex element templates for Anatomic Pathology (AP) observations can be reduced to 53 generic templates, leaving out only 17 templates very specific for organ and/or disease. Among those 53 templates 28 are describing UICC-TNM staging, ICD-O-classification, and grading. Further 15 templates describe the results from marker investigations. Almost all of the terms, used in those templates could be mapped to SNOMED CT. All of the generic elements have their "organ specific" counterparts by assigning them to one of 20 organs and invasive or noninvasive cancer, respectively. Studying the structure of generic and specific terms it becomes obvious that any AP observation: - occurs always in a context; - consists of three basic elements (target of observation, property of observation, additional qualifiers, added by value sets for coded data). CONCLUSIONS: If a machine-readable terminology is aimed to preserve all the information of native speaking, then two principal solutions exist: - ystematic consideration of all the aspects mentioned above in each single term; - ocusing on the generic elements of terms and combining this with the structure of communication, reflecting the non-obvious elements of the terminology. The fastest way for establishing an interface terminology is the first approach, which lists all of the terms needed for e.g. a checklist in a comprehensive manner (precoordination).

A 10-year analysis of cutaneous mesenchymal tumors (sarcomas and related entities) in a skin cancer center.

BACKGROUND: Mesenchymal neoplasms (sarcomas) of skin are rare. Patients with sarcomas were analyzed over the last decade. METHODS: Over a 10-year period, we conducted a retrospective analysis of patients diagnosed and treated in an urban academic teaching hospital in Saxony, Germany. Clinical and pathologic files were used. RESULTS: We identified 65 adult patients with 67 primary cutaneous sarcomas. The mean age was 73.1 (± 15.5) years with a male predominance (78.5%). None of the sarcomas was detected by a skin cancer screening program. The diagnosis was atypical fibroxanthoma (n = 41 patients with 43 tumors), cutaneous angiosarcoma (eight), dermatofibrosarcoma protuberans (two), nodular epithelioid cell sarcoma (one), Kaposi sarcoma (three), leiomyosarcoma (five), malignant fibrous histiocytoma (two), fibromyxoid sarcoma (one), and cutaneous angiomyxoma (two). The preferred tumor localization was the head and neck area (44 patients). Follow-up was 0.5-5.5 years (mean 18 ± 12 months). We observed metastatic spread of atypical fibroxanthoma in 12.5%, demonstrating that this type of sarcoma can run an aggressive course. Mohs surgery is still the cornerstone of treatment, although new options in palliative or adjuvant treatment are available. CONCLUSIONS: Mesenchymal neoplasms (sarcomas) are an important group of cutaneous malignancies. Awareness needs to be improved.

A 10-year analysis of primary cutaneous malignant melanoma with sentinel lymph node biopsy and long-term follow-up.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is an important tool for accurate staging of patients with melanoma. There is an ongoing debate whether the procedure provides therapeutic benefits or not. OBJECTIVE: We wanted to analyze 10-year data from an academic teaching hospital. PATIENTS AND METHODS: During 1999-2009, 977 patients with early cutaneous melanoma have been treated. Of these, 419 patients had tumors ≥ 1 mm thickness. Patients with head and neck tumors were excluded, leaving 364 patients (202 men and 162 women). SLNB was not performed in 163 patients but was performed in 201 patients. For correction of bias, tumors >4 mm thickness were excluded from further statistical analysis. RESULTS: The detection rate of SLN was 94.4%. False negative SLN were observed in 8.9%. Adverse effects occurred in 5.5%. The rate of positive SLNB was 16.4% and lymph node involvement 20%. Patients undergoing SLNB had a lower relapse rate (10.6% vs. 33.3%; P < 0.001). The most important finding is an almost 50% lower total death rate and melanoma-related death rate in the SLNB subgroup (P < 0.001 for both). CONCLUSIONS: Sentinel lymph node biopsy is an accurate instrument for melanoma staging to detect occult regional lymph node involvement. Data suggest a positive effect on relapse-free survival. The observation of improved long-term survival needs validation in prospective multicenter trials. The limitations of this study were that it was a single center retrospective analysis.

Classification of vascular disorders in the skin and selected data on new evaluation and treatment.

Cutaneous vascular disorders are common. They include arteries, veins, and lymphatic vessels, or a mixture of them. In this review, we discuss classification, new developments in understanding and treatment of vascular diseases. We focus on infantile hemangiomas and drug therapy, vasculitides with new vasculitic syndromes, yellow nail syndrome and localized lymphatic malformations. Benign cutaneous vascular lesions may be a sign of severe internal diseases. In many cases multidisciplinary treatment is important. The dermatologist can often act as a pilot for these patients.

Short-term outcome of extra-levator abdominoperineal excision for rectal cancer.

BACKGROUND: Extra-levator abdominoperineal excision (ELAPE) has been introduced to avoid oncologic problems encountered with conventional abdominoperineal excision (APE) such as high rates of inadvertent bowel perforation and of positive circumferential resection margin. We compare our short-term results of this new approach with a historic patient cohort. PATIENTS AND METHODS: From 1997 until 2010, we performed 46 consecutive conventional APE and 28 ELAPE after neoadjuvant therapy with a macroscopically complete resection in the true pelvis. Patient data was prospectively collected in our colorectal tumor database. Patient and tumor characteristics were compared as were the rates of inadvertent bowel perforation, of circumferential margin involvement, and of wound abscesses. RESULTS: The rates of inadvertent bowel perforation, of circumferential margin involvement, and of wound abscesses were 15.2% vs. 0 (p = 0.04), 4.9% vs. 0 (p = 0.511), and 17.4% vs. 10.7% (p = 0.518), respectively, in the conventional APE vs. ELAPE group. CONCLUSION: With a significant reduction of the bowel perforation rate and a reduction of circumferential margin involvement and wound abscess formation, ELAPE improves important surrogate parameters for local recurrence rate and survival.

Combined cetuximab and volumetric modulated arc-radiotherapy in advanced recurrent squamous cell carcinoma of the scalp.

A 77-year old male patient presented with an ulcerated exophytic tumor (T2, N0, M0) with three macroscopically visible satellite metastases in the right temporo-occipital region. Mohs surgery could not control the disease due to lymphangiosis carcinomatosa and perineural infiltration, and recurrence of satellite skin metastases. Re-staging demonstrated a T2, N1, M0 profile (stage III, AJCC). Chemotherapy was limited by the patient's co-morbidities. Therefore, we used targeted therapy with monoclonal anti-epidermal growth factor receptor antibody cetuximab in combination with volumetric modulated arc- radiotherapy (VMAT). Cetuximab was well tolerated except for the loading dose when the patient developed fever chills. To verify the correct application of VMAT, it was applied to a 3-dimensional measuring phantom prior to the patient's first treatment session. To minimize these tolerances, patient set-up was checked and corrected by orthogonal fluoroscopic images recorded daily by the on-board imager used in our Varian accelerator. The average daily beam time was 6 min (6 arcs, 767 monitor units); the total treatment time including patient set-up and set-up correction was less than 20 min. Combined therapy was well tolerated and complete remission was achieved.

Pyoderma gangraenosum.

PURPOSE OF REVIEW: To describe current progress in understanding pyoderma gangraenosum, illustrate clinical observations and discuss therapeutic interventions. RECENT FINDINGS: The proline-rich, glutamic acid-rich, serine-rich and threonine-rich (PEST) family of protein tyrosine phosphatases is a critical regulator of adhesion and migration. PSTPIP1 is a cytoskeleton-associated adaptor protein that links PEST-type phosphatases to their substrates. This pathway seems to be involved in diseases related to pyoderma gangraenosum such as chronic inflammatory bowel disease and aseptic abscesses syndrome. Pyoderma gangraenosum is one of the most common extra-intestinal manifestations of chronic inflammatory bowel disease. In multivariate analyses, pyoderma gangraenosum was significantly and independently associated with black African origin, familial history of ulcerative colitis, uninterrupted pancolitis as the initial location of inflammatory bowel disease, permanent stoma, eye involvement and erythema nodosum. The treatment of choice for idiopathic pyoderma gangraenosum is systemic corticosteroids but cyclosporine A, mycophenolate mofetil and tumour necrosis factor-alpha inhibitors have been successful to control pyoderma gangraenosum as second line or adjuvant options. In addition, small studies have been published with successful therapeutic intervention using alefacept, visilizumab or anakinra but controlled trials are warranted. Although systemic immunosuppressants remain the choice therapy for most cases of pyoderma gangraenosum, a local approach should be considered in localized disease. Recently, topical tacrolimus has successfully been used as an off-label drug in localized disease. SUMMARY: By a better understanding of the underlying pathology and recent drug developments patients with pyoderma gangraenosum will benefit. For several new drugs, however, controlled trials are warranted.

Practicability of quality goals for the treatment of rectal cancer.

PURPOSE: In 2007, the German Working Group "Workflow Rectal Cancer II" published 19 quality indicators with 36 quality goals for the treatment of rectal cancer. We investigate whether these parameters are practicable in a specialized coloproctologic unit. PATIENTS AND METHODS: We included 578 consecutive patients with rectal cancer who were treated in our institution from January 2000 to December 2008. Patient data were collected in a prospective database. Follow-up was conducted in a colorectal tumor clinic. Data were analyzed for the defined reference groups, and the results were compared with the quality goals. RESULTS: Median follow-up was 54.4 (range 1-116) months. We achieved 19 of the 36 defined quality goals. Among these were important parameters such as the rate of postoperative mortality (0.9%), the rate of intraoperative local tumor perforation (2.2% for anterior resection and 8.5% for abdominoperineal excision), the 5-year local recurrence rate (5.9% stages I-III), and the 5-year overall survival rates for stages yII and II (79.9%), and stages yIII and III (60.7%) for patients with microscopically negative resection margins. CONCLUSION: Most of the defined quality goals can be achieved in a specialized coloproctologic unit. The debate on quality goals has the potential to enable further improvement in the care of rectal cancer patients.

N-domain of human adhesion/growth-regulatory galectin-9: preference for distinct conformers and non-sialylated N-glycans and detection of ligand-induced structural changes in crystal and solution.

Human tandem-repeat-type galectin-9 is a potent adhesion/growth-regulatory effector via lectin capacity of its N- and C-terminal domains. This bioactivity prompted further crystallographic study of the N-domain, combined with analysis in solution. Binding of lactose markedly increased the N-domain's resistance to thermal denaturation. Crystallography revealed its intimate contact profile, besides detecting an extension of the beta-sandwich fold by an antiparallel beta-strand F0 aligned to the C-terminal F1 strand. Ligand accommodation in its low-energy conformation leads to a movement of Arg87's side chain. As consequence, the ligand's glucose moiety and Arg87 become hydrogen bonded. The resulting predictions for spatial parameters in solution were verified by determining (a) the pattern of magnetization transfer from the protein to protons of lactose and Forssman disaccharide by NMR spectroscopy and (b) the ellipticity changes at wavelengths characteristic for Trp/Tyr residues in near-UV CD spectroscopy. Whereas solid-phase assays confirmed a previously noted tendency for homo- and heterotypic aggregation, gel filtration and ultracentrifugation disclosed monomeric status in solution, in line with crystallographic data. Using cell mutants with defects in glycosylation, this lectin domain was shown to preferentially bind N-glycans without alpha2,3-sialylation. Since proximal promoter sequences were delineated to diverge markedly among galectin genes and resulting differences in expression profiles were exemplarily documented immunohistochemically, the intrafamily diversification appears to have assigned this protein to a characteristic expression and activity profile among galectins. Our data thus take the crystallographic information to the level of the lectin in solution and in tissues by a strategic combination of spectroscopic and cell/histochemical assays.

Comparative genomic hybridization-based oncogenetic tree model for genetic classification of breast cancer.

OBJECTIVE: To describe a genetic progression pathway in breast cancer by a maximum likelihood-based tree model representing the dependencies between chromosomal imbalances. STUDY DESIGN: One hundred six cases were studied by comparative genomic hybridization, followed by maximum likelihood estimation of an oncogenetic tree model. RESULTS: The tree model identified 3 clusters with correlated chromosomal imbalances. The first cluster included losses at 4q, 5q, 6q, 9p, 13q and a gain at 17q; the second cluster included gains at 1q, 8q, 16p and 20q; the third cluster included losses at 8p, 11q, 16q and 18q. The imbalances nearest the root of the tree were the loss at 13q (cluster 1), the gain at 1q (cluster 2) and the loss at 18q (cluster 3), reflecting an early change in breast cancer evolution. Cox regression analysis revealed the tumor stage and the grade as relevant for overall survival (p = 0.001) and the tumor stage, the grade and the loss at 16q as relevant for disease-free survival (p = 0.001). CONCLUSION: Methods like oncogenetic tree analysis provide insights into the genetic progression of breast cancer and may extract relevant markers detected by screening methods like comparative genomic hybridization for further studies.

Deep ulcer shaving combined with split-skin transplantation in distal calciphylaxis.

Calciphylaxis is a cause of painful deep ulcers. There is controversy about best wound management in this disease. A retrospective study of inpatients during the 3 years was made. Seven calciphylaxis patients were identified. All patients suffered from various associated pathologies including diabetes mellitus type II and chronic renal insufficiency. Ulcers were treated by aggressive and deep shaving combined with autologous split-skin grafting in the same session. A 30% to 90% take rate of the grafts eventually with a complete ulcer healing in 6 of 7 patients was achieved. No patient developed a deep cutaneous infection or sepsis. All patients are still alive except one. The single death was related to cardiovascular complications. In distal calciphylaxis, aggressive ulcer surgery with defect closure offers a marked improvement in quality of life and prevents early deep skin infections and sepsis as major causes of mortality.

Tumescent suction curettage versus minimal skin resection with subcutaneous curettage of sweat glands in axillary hyperhidrosis.

BACKGROUND: Axillary hyperhidrosis is a common problem with a strong negative impact on professional and social life. Various types of surgical procedures have been developed for its treatment. OBJECTIVE: We want to compare efficacy and risk-benefit ratio of two local surgical procedures, i.e., the minimal skin excision with subcutaneous curettage (Method A) and tumescent liposuction curettage (Method B). METHODS: A total of 163 patients with primary axillary hyperhidrosis as assessed by positive iodine-starch test were included. The age range of patients was 16 to 61 years (mean 28 years), including 33 males and 129 females. A total of 125 underwent Method A, and 37 were treated by Method B. Both procedures were performed in tumescent anesthesia. The mean follow-up was 21 months (Method A) and 48 months (Method B). The outcome was evaluated by patient's global assessment and by Minor's starch test. Patient satisfaction was scored as "satisfied,""partially satisfied," or "dissatisfied." Adverse effects, complications, hospitalization time, and time to return to work were recorded and compared for both methods. In patients who underwent Method A, scar formation was assessed only for the first axilla (n=99). RESULTS: In Method A, the rate of residual sweating was 12.0%. The relapse rate was 1.0% of patients or 2% of axillae. In Method B, the relapse rate was 16.2% of patients or 14.5% of axillae within 12 months. If we consider both the relapses and the residual sweating, this modified relapse rate per axilla was 12.8% for Method A and 14.5% for Method B. Patients who underwent Method B had significantly less pain, no atrophic or hypertrophic scars, and no complications such as wound infections, bleeding (with the need of a second operation), or delayed healing. Using Method A, the stay in hospital was on average 5.8 days per patient or 3.2 days per axilla. Mean time to return to work was 8.8+/-3.5 days. For Method B, the procedure was performed in an outpatient setting. The mean time to return to professional work was 1.3+/-0.8 days. The total satisfaction rate was 97% for Method A and 89.2% for Method B, respectively. CONCLUSIONS: As shown by this study, minor skin resection with subcutaneous curettage of axillary sweat glands (Method A) is somewhat more effective in permanent reduction of hyperhidrosis than suction curettage. The minimal invasiveness of suction curettage and the minimal scarring, however, are significant advantages over excisional surgery. Downtime after surgery is significantly shorter for suction curettage. Therefore, suction curettage might be the surgical treatment of choice for axillary hyperhidrosis.

Chromosomal genotype in breast cancer progression: comparison of primary and secondary manifestations.

The purpose of this study was to compare the chromosomal genotype between breast cancers with and without secondary manifestations and between primary tumors and their secondary manifestations. Eighty six breast cancers, twenty lymph node metastases, ten distant metastases and ten local recurrences were analyzed by comparative genomic hybridization. Tumors with local recurrences showed significant more frequent losses at 2q32 than the tumors without recurrences. Lymph node positive cases showed significant more frequent losses at 9p21 than node negative cases. Lymph node metastases exhibited significant more frequent losses at 7q11, 14q24.3-q31 and 17q22-q24 than their primary tumors. In cases with distant metastases, losses at 5q23 were more frequent than in those without, but not reaching the significance level. The distant metastases showed significant more frequent losses at 5p15, 12q24 and 17q22-q24 than the primary tumors. These results reveal strong evidence that the potential for progression is determined in the primary tumor and that different ways of the development of local recurrences, lymph node and distant metastases exist. After confirmation of the results by interphase FISH on tissue micro arrays, the detection of these specific chromosomal imbalances may contribute to a more individual prediction of prognosis in breast cancer.

Isolated plexiform schwannoma of the hand.

BACKGROUND: The plexiform schwannoma, a peripheral nerve sheath tumor, is a very rare entity. But dermatologists should be familiar with since they may be the first who make diagnosis possible by taking a deep biopsy. MAIN OBSERVATION: A 24-year-old male presented with multiple asymptomatic subcutaneous nodules of the palmar side of his right hand. Histologic investigations revealed a plexiform schwannoma with numerous Antoni-A areas. There was no evidence of neurofibromatosis type 1 or 2. CONCLUSIONS: Plexiform schwannoma of the hand is a rare nerve sheath tumor. In individual (symptomatic) cases hand surgery is an option that needs a critical indication. In every case histologic investigations are mandatory to confirm the diagnosis and not to overlook the malignant variant of this disease.

Tumor necrosis factor-alpha inhibitor-induced psoriasis or psoriasiform exanthemata: first 120 cases from the literature including a series of six new patients.

Tumor necrosis factor-alpha (TNFalpha) inhibition is effective in the treatment of moderate-to-severe psoriasis. We report on 120 patients from the literature including six new patients (three women and three men) who developed pustular lesions during treatment with TNFalpha inhibitors. We identified 72 women and 36 men (several papers did not specify the gender of patients) with an age range of 13-78 years (mean 42.3 years). The primary diagnoses were rheumatoid arthritis (n = 61), ankylosing spondylitis (n = 21), psoriasis (n = 10), Crohn disease (n = 8), SAPHO (synovitis acne pustulosis hyperostosis osteitis) syndrome (n = 3), psoriatic arthritis (n = 2), and other diagnoses (n = 15). Psoriasis (except palmoplantar pustular type) was the most common adverse effect during anti-TNFalpha treatment (n = 73), followed by palmoplantar pustular psoriasis (n = 37) and psoriasis of the nail (n = 6), sometimes combined in the same patient. Palmoplantar pustulosis and psoriasiform exanthema was the diagnosis in ten patients each. A positive personal history of psoriasis was recorded in 25 patients. A positive family history was noted in eight patients. No data about personal (n = 7) or family history (n = 46) were available in a number of patients. Newly induced psoriasis was diagnosed in 74 patients whereas an exacerbation or aggravation of a pre-existing psoriasis was noted in another 25 patients. All three TNFalpha inhibitors available on the market were involved: infliximab (63 patients), etanercept (37 patients), and adalimumab (26 patients). Several patients were treated with more than a single TFNalpha inhibitor. The timing of cutaneous adverse effects (psoriasis and psoriasiform rash) varied considerably among patients, ranging from after a single application to a delayed response of up to 63 months after initiation of treatment. The mean time to appearance of the cutaneous adverse effect for all TNFalpha inhibitors was 9.5 months. Cessation of the responsible TNFalpha inhibitor was carried out in 47 patients either alone or in association with adjuvant anti-psoriatic therapy (mostly topical). This resulted in complete remission in 21 patients, partial remission in 20 patients, and stable disease in another three patients; in the other three patients, the outcome was not reported. TNFalpha inhibition was continued in 47 patients but anti-psoriatic adjuvant therapy was introduced. The outcome in this group was complete remission in 22 patients, partial remission in 25 patients, and stable disease in 2 patients. The response rate (complete remission plus partial remission) was 93.2% and 95.9%, respectively, in each group. In six patients, switching from one TNFalpha inhibitor to another one immediately after cutaneous adverse effects occurred resulted in an improvement in five patients. In nine patients, a second TNFalpha inhibitor was initiated after a break in TNFalpha inhibition. The response to a second or third drug in these patients was mixed. The underlying pathomechanisms of induction of psoriasis or psoriasiform exanthemata by TNFalpha inhibitors remain elusive but there is reason to assume that induction of such adverse events has more than one pathophysiology.