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Background Pemphigus vegetans is a rare variant of pemphigus vulgaris, accounting for 1–2% of all pemphigus diseases. Systemic corticosteroids are the therapy of first choice in combination with immunosuppressants as steroid-sparing agents. Objective To highlight the exceptional but successful use of minocycline/nicotinamide monotherapy in pemphigus vegetans. Methods A review of the literature to date about pemphigus vegetans with special emphasis on therapy was performed. Due to its rarity, multiple anecdotal reports without long-term follow-up are available and prospective controlled trials are lacking. Only one retrospective study from Tunisia includes 17 patients with pemphigus vegetans. Results We present a 76-year-old woman with pemphigus vegetans achieving complete response to a minocycline/nicotinamide monotherapy at onset and at relapse of the disease. Treatment has been discontinued after repeated direct immunofluorescence (DIF) of previously affected normal skin and anti-desmoglein 3 antibodies had become negative. In addition, DIF of previously involved oral mucosa was negative. During long-term follow-up clinical remission has been maintained for more than 5 years. Up to now, negative results of serial performed indirect immunofluorescence and desmoglein ELISA testing also predict immunological remission. Conclusion In our patient and in a case with oesophageal involvement, published more than 20 years ago, clearly the benefit of minocycline/nicotinamide monotherapy was demonstrated. We propose to consider minocycline/nicotinamide as first-line monotherapy in pemphigus vegetans, especially in elderly patients with comorbidities and contraindications to standard therapy, as it avoids the toxicities of systemic corticosteroids and immunosuppressants.

ZusammenfassungHintergrund und Ziel der Studie Die Purpura pigmentosa progressiva (PPP, Morbus Schamberg) ist eine seltene gutartige chronische Dermatose, die haufig als Vaskulitis oder Gerinnungsstorung fehldiagnostiziert wird. Obwohl die betroffenen Patienten eine wesentliche Einschrankung ihrer Lebensqualitat erfahren, gibt es bislang keine etablierte Therapie. Das Ziel unserer doppelzentrischen Fallserienuntersuchung war die Evaluation der Effektivitat und Vertraglichkeit der Antioxidantien Rutosid und Ascorbinsaure als Kombinationstherapie bei PPP. Patienten und Methodik Es erfolgte die retrospektive Datenauswertung von 35 PPP-Patienten, die zwischen 2004 und 2011 mit 2 × 50 mg Rutosid und 1 000 mg Ascorbinsaure taglich behandelt wurden. Die mittlere Behandlungsdauer betrug 8,2 Monate. Ergebnisse Bei 71,4 % der Patienten kam es zu einer kompletten Abheilung der Hautveranderungen wahrend es bei 20,0 % zu einer mindestens 50%igen Verbesserung der Symptome kam, einhergehend mit einer Steigerung der Lebensqualitat. Neun Studienteilnehmer (25,1 %) erlitten nach dem Absetzen der Therapie einen Ruckfall. Bei sieben von ihnen wurde daraufhin die Therapie wieder eingeleitet und fuhrte in allen Fallen zu einem erneuten Ansprechen. Bei drei Patienten kam es zu leichten unerwunschten Wirkungen. Patienten mit einer kurzeren Erkrankungsdauer zeigten bessere Behandlungsergebnisse, eine kurzere Latenzzeit bis zum Ansprechen auf die Therapie und ein geringeres Ruckfallrisiko. Schlussfolgerung Die orale Therapie mit Rutosid und Ascorbinsaure eroffnet eine effektive und gut vertragliche Therapieotion bei PPP. Um ein gutes therapeutisches Ergebnis zu erzielen, wird eine fruhe Therapie empfohlen.

SummaryBackground and Objectives Progressive pigmented purpuric dermatosis (PPPD, Schamberg disease) is a rare benign, but chronic dermatosis frequently misdiagnosed as vasculitis or bleeding disorder. Although affected patients experience significant impairment in quality of life no effective treatment has been established. The aim of our two center case series was to evaluate efficacy and tolerability of the antioxidants rutoside and ascorbic acid as combination treatment for PPPD. Patients and Methods A retrospective review was performed on 35 patients with PPPD treated with 2 × 50 mg rutoside and 1 000 mg ascorbic acid daily between 2004 until 2011. The mean treatment duration was 8.2 months. Results 71.4 % of the participants experienced complete clearance and 20.0 % an improvement of more than 50 %, accompanied by increased quality of life. Nine participants (25.1 %) relapsed after discontinuation. In seven, rutoside and ascorbic acid was re-initiated, and all responded again. Only three participants reported mild adverse effects. Participants with shorter disease duration showed better therapeutic success, shorter time to response and lower risk of recurrence. Conclusion Oral rutoside and ascorbic acid may be an efficient and well tolerated treatment for PPPD. Early treatment is recommended to achieve best clinical outcome.

In this prospective, cross-sectional, multicenter study, we assessed clinical and laboratory characteristics from patients with cutaneous lupus erythematosus (CLE) using the Core Set Questionnaire of the European Society of Cutaneous Lupus Erythematosus (EUSCLE). 1002 (768 females, 234 males) patients with different subtypes of CLE, such as acute CLE (ACLE, 304 patients), subacute CLE (SCLE, 236 patients), chronic CLE (CCLE, 397 patients), and intermittent CLE (ICLE, 65 patients), from 13 European countries were collected and statistically analyzed by an SPSS database. The main outcome measures included gender, age at onset of disease, LE-specific and LE-nonspecific skin lesions, photosensitivity, laboratory features, and the criteria of the American College of Rheumatology (ACR) for the classification of systemic lupus erythematosus. The mean age at onset of disease was 43.0±15.7 years and differed significantly between the CLE subtypes. In 347 (34.6%) of the 1002 patients, two or more CLE subtypes were diagnosed during the course of the disease and 453 (45.2%) presented with LE-nonspecific manifestations. Drug-induced CLE and Sjögren's Syndrome had the highest prevalence in SCLE patients (13.1% and 14.0%, respectively). Photosensitivity was significantly more frequent in patients with ACLE, SCLE, and ICLE compared with those with CCLE. The detection of antinuclear antibodies such as anti-Ro/SSA and anti-La/SSB antibodies revealed further significant differences between the CLE subtypes. In summary, the EUSCLE Core Set Questionnaire and its database facilitate the analysis of clinical and laboratory features in a high number of patients with CLE and will contribute to standardized assessment and monitoring of the disease in Europe.

Treatment of skin manifestations in systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and dermatomyositis (DM) is based on the results of only few randomized controlled trials. The first-line treatment for disfiguring and widespread cutaneous involvement in SLE is antimalarials, but some patients are therapy resistant. Recently, the monoclonal antibody belimumab was approved for SLE as an adjunct therapy for patients with autoantibody-positive disease who despite standard therapy show high disease activity, intolerance of other treatments, or an unacceptably high need for corticosteroids. However, a validated skin score has not been used to confirm the efficacy of belimumab on mucocutaneous manifestations. In SSc, another multi-systemic progressive disease, involvement of the lung, kidney, and the heart is frequently treated with corticosteroids and immunosuppressives, but therapeutic modalities for cutaneous lesions, such as skin sclerosis and digital ulcers, are limited. In the past years, treatment with the endothelin-receptor antagonist bosentan has been proven to reduce the occurrence of new digital ulcers in SSc patients but has no or limited effect on healing of digital ulcers. DM is an idiopathic autoimmune disease characterized by inflammation of the muscles and skin, which is treated with immunosuppressives. Corticosteroids are the first-line treatment for muscle involvement in DM, but skin lesions often flare by reduction or discontinuation. In summary, there is a high unmet need for new therapeutic strategies focusing on skin involvement in systemic autoimmune diseases. Therefore, innovative designs of randomized controlled trials with validated skin scores are warranted to develop new therapeutic strategies for patients with cutaneous manifestations.

In the first part of the review, topical agents and first-line systemic treatment options for cutaneous lupus erythematosus were discussed whereas in the second part, recent information on efficacy, dosage, and side effects for further systemic treatment options are described in detail. In contrast to other immunosuppressive agents, such as azathioprine, cyclophosphamide, and cyclosporine, methotrexate has recently received more attention in the treatment of the disease. Further second-line treatment includes retinoids, dapsone, and mycophenolate mofetil. Because of severe side effects or high costs, other agents, such as thalidomide or high-dose intravenous immunoglobulins, are reserved for severe recalcitrant CLE. Biologics, ie, rituximab, have been used to treat systemic lupus erythematosus; however, in CLE, most biologics have only been applied in single cases. In addition to successful treatment, induction of CLE subtypes by biologics has been reported. In conclusion, many treatment options exist for CLE, but not many are supported by evidence from randomized controlled trials.

Epidemiological data and standard European guidelines for the diagnosis and treatment of cutaneous lupus erythematosus (CLE) are lacking in the current literature. In order to provide a standardized tool for an extensive consistent data collection, a study group of the European Society of Cutaneous Lupus Erythematosus (EUSCLE) recently developed a Core Set Questionnaire for the assessment of patients with different subtypes of CLE. The EUSCLE Core Set Questionnaire includes six sections on patient data, diagnosis, skin involvement, activity and damage of disease, laboratory analysis, and treatment. An instrument like the EUSCLE Core Set Questionnaire is essential to gain a broad and comparable data collection of patients with CLE from different European centres and to achieve consensus concerning clinical standards for the disease. The data will also be important for further characterization of the different CLE subtypes and the evaluation of therapeutic strategies; moreover, the EUSCLE Core Set Questionnaire might also be useful for the comparison of data in clinical trials. In this review, the impact of the EUSCLE Core Set Questionnaire is discussed in detail with regard to clinical and serological features as well as therapeutic modalities in CLE. Lupus (2010) 19, 1144—1152.

There exists no treatment of choice for follicular mucinosis (FM). Historically two distinct entities of FM have been proposed: FM of children and young adults not associated with other diseases ('idiopathic' FM), and FM in elderly patients associated with mycosis fungoides and Sezary syndrome ('lymphoma-associated' FM). Nowadays it is suggested that 'idiopathic' FM might represent a localized form of cutaneous T-cell lymphoma. Six patients with 'idiopathic' FM were treated with hydroxychloroquine (HCQ) at a dose of 200 mg three times daily for 10 days followed by a dose adjusted to the ideal body weight, usually 200 mg twice daily. All patients showed an improvement of 'idiopathic' FM already after 6 weeks and a complete remission with full hair regrowth after 2-5 months of HCQ therapy. In all patients no relapse occurred during follow up of between 3 and 23 years and no patient developed lymphoma. We conclude that HCQ is a highly effective therapy without significant side-effects in the treatment of so-called 'idiopathic' FM.

Background Lupus erythematosus tumidus (LET) is a rare disease which was first described in 1909 but has not always been considered as a separate entity of cutaneous lupus erythematosus (CLE) in the international literature. Objectives To compare characteristic features of different subtypes of CLE and to analyse whether LET can be distinguished as a separate entity in the classification system of the disease. Methods The study involved 44 patients with CLE, including 24 patients with LET, 12 with discoid lupus erythematosus (DLE) and eight with subacute CLE (SCLE), from two centres in Germany. A core set questionnaire and an SPSS database were designed to enable a consistent statistical analysis. Results Location of skin lesions did not differ significantly between the CLE subtypes; however, the activity score was significantly lower in LET than in DLE (P < 0.01), and the damage score was significantly lower in LET than in SCLE (P < 0.01) and DLE (P < 0.01). Photosensitivity and antinuclear antibodies were confirmed to be different in LET compared with SCLE and DLE but without statistical significance. Moreover, histological analysis of skin biopsy specimens showed that abundant mucin deposition is significantly more present in LET compared with SCLE (P < 0.01) and DLE (P < 0.01) while prominent interface dermatitis and alteration of hair follicles were absent in LET. Conclusions Several significant differences were found between LET and other subtypes of CLE with regard to clinical, histological and laboratory parameters. These data strongly indicate that LET should be defined as a separate entity in the classification of CLE.

Bei Kollagenosen handelt es sich um eine Gruppe chronischer Autoimmunerkrankungen, die den systemischen Lupus erythematodes (SLE), die progressiv systemische Sklerodermie (PSS), die Dermato- (DM) und Polymyositis (PM) sowie die gemischte Bindegewebserkrankung („mixed connective tissue disease“, MCTD) und das Sjogren-Syndrom (SS) umfassen. Im Kindesalter kommen diese Erkrankungen seltener vor als bei Erwachsenen, manifestieren sich klinisch aber sehr vielfaltig. Unspezifische Allgemeinsymptome wie Mudigkeit, Fieber und Gewichtsverlust gehen haufig einer systemischen Organmanifestation voraus. In diesem Ubersichtsartikel werden aktuelle Angaben uber klinische Erscheinungsformen, diagnostisches Prozedere und therapeutische Strategien der Kollagenosen zusammengefasst und insbesondere auf spezifische Probleme im Kindesalter eingegangen.

Lupus erythematosus (LE) is an inflammatory autoimmune disease, characterized by a heterogeneous clinical presentation. The skin lesions are one of the most frequent symptoms of the disease and present with a broad spectrum of LE-nonspecific and LE-specific cutaneous manifestations. Therefore, the development of a classification for skin lesions in the disease has proven difficult. For example, the LE-nonspecific cutaneous manifestations include livedo racemosa, thrombophlebitis, and leukocytoclastic vasculitis and can be associated with high disease activity and systemic organ involvement. The LE-specific cutaneous manifestations encompass the subtypes of cutaneous lupus erythematosus (CLE): acute CLE, subacute CLE, and chronic CLE, such as discoid LE, chilblain LE, and LE profundus/panniculitis. In the “Duesseldorf Classification”, LE tumidus is included as a separate entity, named intermittent CLE. In this chapter, we describe the characteristic features of the various cutaneous manifestations of the disease.

Cutaneous lupus erythematosus (CLE) is a chronic inflammatory autoimmune disease with a broad spectrum of clinical manifestations and a variable course. In numerous investigations, it has been shown that exogenous factors, such as UV-light and drugs, can induce this disease. However, not all clinical aspects can be explained and therefore, the pathogenesis of CLE is currently under extensive research. The various cutaneous manifestations of LE are divided into LE-nonspecific and LE-specific skin disease based on histologic criteria. LE-nonspecific manifestations are mostly associated with systemic LE but can also occur in other diseases and include particularly vascular skin lesions such as pe-riungual telangiectases. LE-specific skin disease includes the subtypes of CLE such as acute cutaneous LE (ACLE), subacute cutaneous LE (SCLE), chronic cutaneous LE (CCLE), and intermittent CLE (ICLE). The subdivision of these subtypes with different prognosis and course is supported by genetic, clinical, histologic, and immunoserologic findings. The subtypes of CLE require a specific morphological and clinical analysis, which is described in the first part of this review. In the second part of this review, further diagnostic procedures and therapeutic strategies in patients with CLE are discussed.

Objective The aim of the study was to assess the efficacy and safety of fumaric acid esters (FAEs) in patients with cutaneous lupus erythematosus (CLE). Methods In this 24-week, prospective, open-label, phase II pilot study, 11 patients with CLE, refractory to topical corticosteroids, were included. The primary endpoint of the study was the evaluation of the efficacy of FAEs after 24 weeks of treatment as assessed by the Revised Cutaneous Lupus Disease Area and Severity Index (RCLASI). Results Compared to baseline, significant improvement in the mean total RCLASI activity score and the mean RCLASI activity score for skin lesions was observed in week 12 ( p = 0.002, p = 0.002, respectively) and in week 24 ( p = 0.009, p = 0.009, respectively). Most common adverse events included abdominal cramps and headache. Conclusions FAEs could be an alternative and safe treatment in patients with therapy-refractory CLE; however, randomized controlled trials are warranted to evaluate the efficacy and safety of FAEs in this disease.

Neutrophilic urticarial dermatosis (NUD) comprises a particular autoinflammatory condition within the spectrum of aseptic neutrophilic dermatoses characterized by a distinct urticarial eruption clinically and a neutrophilic dermatosis histopathologically.In this study, we reviewed skin biopsies of lesional skin of patients seen in our outpatient clinic for autoimmune dermatoses and in allergy department from 1982 to 2014 that fulfilled these criteria.A total of 77 biopsies from 50 patients were analyzed histopathologically. Included were cases of Schnitzler syndrome, Still disease, systemic lupus erythematosus, Sjögren syndrome, cryopyrin-associated periodic syndrome, primary biliary cirrhosis, inflammatory bowel disease, and those that had signs of systemic inflammation not otherwise specified, that is, fever, arthritis, leukocytosis, and elevated erythrocyte sedimentation rate. A control cohort was defined as including a total of 70 biopsies from 50 patients comprising neutrophilic urticaria (pressure-induced and not pressure-induced), conventional urticaria, lupus erythematosus expressing neutrophils, and exanthematous drug reaction of macular type expressing neutrophils.Skin biopsies of NUD revealed a perivascular and interstitial neutrophilic infiltrate focally extending into the epithelia of epidermis, hair follicles, sebaceous and sweat glands, a feature which we termed neutrophilic epitheliotropism. This neutrophilic epitheliotropism proved to be of high sensitivity (83.1%) and lower specificity (74.3%). The histological findings could be substantiated by immunohistochemical markers for leukocytes (elastase and myeloperoxidase), in particular in cases where neutrophils showed uncharacteristic band-like nuclei.Neutrophilic epitheliotropism is a new sensitive and specific histopathological clue for NUD, a histopathological reaction pattern within the spectrum of neutrophilic dermatoses that needs to be differentiated from conventional urticaria.

Cutaneous lupus erythematosus (CLE) is a disease with different subtypes and the new classification system includes acute CLE (ACLE), subacute CLE (SCLE), chronic CLE (CCLE), and intermittent CLE (ICLE). The broad spectrum of skin involvement and the possibility of systemic organ manifestations at the beginning and during the course of CLE require specific diagnostic procedures. Clinical assessment of the cutaneous manifestations is necessary along with a detailed patient's history. The diagnosis of CLE is confirmed by histopathology and immunofluorescence microscopy. Selective laboratory screening and additional diagnostic procedures depending on clinical symptoms are recommended. Photoprovocation tests can be performed to assess photosensitivity in patients with CLE and to support the diagnosis. Recently, a scoring system for the activity of the cutaneous manifestations in CLE has been developed and is now evaluated in several clinical studies. In this review, the classification and the characteristic clinical criteria of the different CLE subtypes as well as the current diagnostic possibilities are emphasized.

The diagnosis of cutaneous lupus erythematosus (CLE) requires a specific diagnostic approach to identify subtypes, to address differential diagnostic considerations, and to rule out systemic organ involvement. In addition to a detailed patient's history and clinical evaluation of the skin, histopathologic and immunofluorescent examination of a skin biopsy as well as laboratory screening are recommended. Photoprovocation tests can be performed to confirm the diagnosis of CLE and to assess photosensitivity in these patients. Recently, a scoring system for the activity of the cutaneous manifestations in CLE has been developed and validated which involves anatomical areas and morphologic signs of the skin lesions. In all subtypes of CLE, antimalarials are still the treatment of choice. Advances in biotechnology have led to the development of several novel agents for the treatment of autoimmune diseases; however, controlled trials have not been performed in patients with CLE. Furthermore, there is need for specific immunointervention, especially for patients who fail to respond to standard therapies. The second part of this review will enable the reader to differentiate CLE from other diseases and to suggest specific diagnostic procedures and treatment approaches.

Cutaneous lupus erythematosus (CLE) is a heterogenous disorder with a wide range of skin manifestations. Therefore, it has been difficult to develop a unifying concept for classifying CLE from the dermatologic perspective in the past. In 2004, the classification system was updated and includes now acute CLE (ACLE), subacute CLE (SCLE), chronic CLE (CCLE), and intermittent CLE (ICLE). Additional rarely described variants are not listed as separate entities but are included in the classical forms. Diagnosis of the different subtypes of CLE is made by considering genetic, clinical, histopathologic, and immunoserologic findings, with a systematic analysis of individual criteria. In the past years, the etiology and pathogenesis of CLE has been subject of intensive research and it has been shown by several groups that exogenous factors, such as ultraviolet light and drugs, can induce CLE. The first part of this review will enable the reader to identify the various clinical manifestations of CLE and to employ characteristic criteria to assess differential diagnostic considerations.

Leukocytoclastic vasculitis (LcV) is the most common form of vasculitis of the skin and usually results from deposition of immune complexes at the vessel wall. It presents in different forms and in association with different diseases. When IgA is the dominant immunoglobulin in immune complexes, systemic involvement is likely in both children and adults (Henoch-Schönlein purpura--HSP). LcV due to IgG- or IgM-containing immune complexes has less systemic involvement and a better prognosis than HSP. Other forms of LcV include cryoglobulinaemic, urticarial and ANCA-associated LcV as well as LcV associated with vasculopathy and coagulopathy in SCLE/SLE or in bacteraemia/sepsis. The aim of diagnostic guidelines is to determine the specific type and systemic involvement of LcV and to identify an underlying cause. Basic work-up should encompass history of drug intake and of preceding infections, biopsy with immunofluorescence, differential blood count, urine analysis and throat swabs. Therapy of immune complex LcV often does not require aggressive therapy due to a usually favourable course. It includes avoidance or treatment of eliciting agents and use of compression stockings to reduce purpura. There are no large prospective randomized controlled studies. Corticosteroids are indicated when there are signs of incipient skin necrosis. In chronic or relapsing LcV we suggest colchicine as a first-line and dapsone as a second-line therapy. Corticosteroids may reduce the incidence of severe renal insufficiency in children according to some studies, but there is no study showing such an effect in adults. Severe systemic vasculitis requires immunosuppressive strategies.

Lichen planus (LP) is an inflammatory skin disorder with a wide range of clinical appearances. The treatment of disseminated and especially erosive forms of LP is often difficult and disappointing. Activated T cells are important in the pathogenesis of LP as indicated by the dermal lymphocytic infiltrate leading to keratinocyte destruction and lesion formation. Similar histologic findings are present in graft-versus-host disease. Since T cells are key players in the development of both disorders and mycophenolate mofetil has been successfully introduced in the treatment of graft-versus-host disease, we have examined the therapeutic potential of this agent in 3 patients suffering from disseminated and erosive LP. Mycophenolate mofetil was well tolerated and induced complete remission in 2 patients, and substantial improvement in the third patient.

The topical therapy of cutaneous lupus erythematosus (LE) consists mainly of corticosteroids which may lead to significant side effects when overused. We report the efficacy of topical tacrolimus as a therapeutic adjunct in 3 patients with cutaneous LE of the face. All patients, 1 with systemic LE and a malar rash, 1 with annular subacute cutaneous LE, the other with a papular variant of subacute cutaneous LE, experienced significant improvement following application of tacrolimus ointment. Treatment with topical tacrolimus was tolerated well without major side effects in all patients. The presented cases are in line with recent reports that topical tacrolimus may be effective in facial LE.

Skin hyperpigmentation induced by minocycline is a well-recognized side effect of minocycline but has rarely been reported for other tetracyclines. Based on a previously reported unusual case of chronic doxycycline abuse in a psychotic patient, we have investigated the nature of the observed pigment changes in the same patient. Histopathologic investigation of lesional skin by light microscopy disclosed hyperpigmentation of the basal keratinocytes and pigment-laden histiocytes in the dermis and subcutaneous fat. Only the pigment in the histiocytes of the upper dermis was reactive for Fontana Masson stain and could be bleached by hydrogen peroxide. The other histiocytes contained iron and calcium deposits as shown by von Kossa and Perls staining as well as by laser microprobe mass analysis. Ultrastructurally, these histiocytes contained amorphous material within the cytoplasm and stored in lysosomal structures. Comparative cathodoluminescence disclosed the presence of doxycycline in affected skin by means of overlapping emission spectra between the patient's skin and pure doxycycline. Taken together, the histomorphologic and ultrastructural changes induced by doxycycline shared several features with cutaneous hyperpigmentation caused by minocycline. Our biophysical findings further suggest a direct deposition of doxycycline, probably chelated with iron and/or calcium, within the lesional skin. Based on the presented unique case and the reviewed literature, only suprapharmacologic doses of doxycycline may be sufficient to cause such pigment changes.

Progressive pigmented purpuric dermatosis (PPPD, Schamberg disease) is a rare benign, but chronic dermatosis frequently misdiagnosed as vasculitis or bleeding disorder. Although affected patients experience significant impairment in quality of life no effective treatment has been established. The aim of our two center case series was to evaluate efficacy and tolerability of the antioxidants rutoside and ascorbic acid as combination treatment for PPPD.A retrospective review was performed on 35 patients with PPPD treated with 2 × 50 mg rutoside and 1,000 mg ascorbic acid daily between 2004 until 2011. The mean treatment duration was 8.2 months.71.4% of the participants experienced complete clearance and 20.0% an improvement of more than 50%, accompanied by increased quality of life. Nine participants (25.1%) relapsed after discontinuation. In seven, rutoside and ascorbic acid was re-initiated, and all responded again. Only three participants reported mild adverse effects. Participants with shorter disease duration showed better therapeutic success, shorter time to response and lower risk of recurrence.Oral rutoside and ascorbic acid may be an efficient and well tolerated treatment for PPPD. Early treatment is recommended to achieve best clinical outcome.

Systemic lupus erythematosus (SLE) is an autoimmune disease with a prevalence of 36.7/100 000 in Germany and a female/male ratio of 4:1. The clinical course is variable, with a broad spectrum of organ manifestations; lupus nephritis develops in about half of all patients.This review is based on a selective search of PubMed and the Cochrane Library, including current guidelines and expert recommendations.Assessment of clinical symptoms, laboratory findings, and optional biopsy results are the basis for early diagnosis of SLE. All patients should be treated with antimalarials as soon as the diagnosis is confirmed. In particular, hydroxychloroquine is associated with a higher rate of remission, fewer relapses, and reduced damage in the course of the disease, even in lupus nephritis. High-dose glucocorticoids should be given only when acutely indicated; immunosuppressives such as azathioprine, methotrexate, or mycophenolate mofetil may be administered to reduce glucocorticoids, according to the EULAR recommendations. Belimumab was recently approved as add-on therapy in autoantibody-positive SLE patients with high disease activity unresponsive to standard treatment. Short-term induction pulse therapy with low-dose intravenous cyclophosphamide, as well as continued mycophenolate mofetil treatment are advances in lupus nephritis.The long-term prognosis for SLE has improved markedly in recent decades because of earlier diagnosis and optimized treatment. Further research and randomized controlled trials are needed for the development of specifically targeted therapies.

Hintergrund und Fragestellung. Die zyklische Neutropenie ist eine seltene kongenitale, autosomal dominant oder sporadisch auftretende hamatologische Erkrankung. Kurzlich konnten als zugrundeliegender Gendefekt sowohl fur die autosomal dominante als auch fur die sporadische Form der zyklischen Neutropenie Mutationen im ELA2-Gen identifiziert werden. Patienten/Methodik. Anhand eines Fallberichtes werden das Krankheitsbild der zyklischen Neutropenie, die Diagnosekriterien, die neuen molekularbiologischen Erkenntnisse und derzeitigen Behandlungsempfehlungen aufgezeigt. Ergebnisse. Regelmasige Blutentnahmen konnten 21-tagige periodische Oszillationen der peripheren neutrophilen Granulozyten aufdecken, wobei die Zahl der neutrophilen Granulozyten zwischen fast normalen und extrem niedrigen Werten schwankte. Der Nadir der neutrophilen Granulozyten hielt jeweils 3–5 Tage an, parallel traten Fieber, Abgeschlagenheit, aphthose Mundschleimhautulzerationen und zervikale Lymphknotenschwellungen auf. Eine Mutationsanalyse genomischer DNA zeigte eine Punktmutation im Intron 4 des ELA2-Gens. Unter einer Therapie mit rekombinantem humanen Granulozytenkolonien stimulierendem Faktor ist die Patientin seit uber 2 Jahren beschwerdefrei. Schlussfolgerungen. Die Diagnose zyklische Neutropenie wurde trotz typischer Anamnese und Manifestation der Erkrankung in den ersten Lebensmonaten erst im Alter von 9 Jahren gestellt. Eine haufige Ursache der verzogerten Diagnosestellung ist neben der Unkenntnis des seltenen Krankheitsbildes die versaumte Differenzierung des Blutbildes im akuten Schub der Erkrankung. Alle Patienten mit zyklischer Neutropenie sollten im internationalen Register fur schwere chronische Neutropenien erfasst werden.

Background: Recently, the induction of subacute cutaneous lupus erythematosus (SCLE) and exacerbation of systemic lupus erythematosus by terbinafine have been reported. Objective: We describe 4 cases of SCLE, one associated with chilblain lupus, which occurred during therapy with oral terbinafine for onychomycosis. Methods: Of 21 consecutive patients with SCLE attending the outpatient dermatology department at Muenster University clinic during a 1-year period, 4 patients with terbinafine-induced SCLE were seen. Patients were examined fully and photographed; histologic findings as well as serologic and follow-up data were evaluated. Results: In addition to high titers of antinuclear antibodies (ANA) with a homogeneous pattern, anti-Ro(SS-A) antibodies were present; in 3 of 4 women, anti-La(SS-B) antibodies were also found. All patients had anti-histone antibodies as in drug-induced lupus and showed the characteristic genetic association of SCLE with the HLA-B8,DR3 haplotype; moreover, in 2 cases, HLA-DR2 was also present. After discontinuation of terbinafine, ANA titers decreased; anti-histone antibodies also became undetectable within 4 ½ months in 3 patients concomitant with subsidence of the SCLE eruption in all patients. Conclusion: Terbinafine is a drug that appears to infrequently induce SCLE with high titers of ANAs and anti-histone antibodies in genetically susceptible persons. (J Am Acad Dermatol 2001;44:925-31.)

Hintergrund: Das nekrobiotische Xanthogranulom ist ein weitgehend unbekanntes Krankheitsbild. Die Haufigkeit der Erkrankung sowie die Beteiligung innerer Organe wurden bisher wohl deutlich unterschatzt. Falldarstellung: Ein Patient wurde mit ulzerierenden, xanthomatoosen subkutanen Knoten, einer Skleritis und Konjunktivitis uberwiesen. Im Labor war die BKS erhoht, es konnten monoklonales IgG-lambda, eine Panzytopenie und spater eine Hypokomplementamie nachgewiesen werden. Auserdem wurden eine Hepatosplenomegalie und Osophagusvarizen festgestellt. Eine Hautbiopsie zeigte ein granulomartieges Infiltrat, das aus Lymphozyten, Plasmazellen, Histiozyten, Schaumzellen sowie Touton'schen und bizarren Riesenzellen vom Fremdkorpertyp und Cholesterinspalten bestand als typische Veranderungen eines nekrobiotischen Xanthogranuloms. Daneben fanden sich auserdem Amyloidablagerungen. Eine Leberbiopsie konnte ebenfalls eine Amyloidose des Parenchyms nachweisen. Weder eine Therapie mit Chlorambucil und Prednisolon noch mit Interferon alpha-2a fuhrten zu einer Besserung. Schlussfolgerung: Neben der Behandlung von Haut- und Augenveranderungen sind weitere Untersuchungen notwendig, da das nekrobiotische Xanthogranulom mit einer malignen Erkrankung assoziiert sein kann und eine Beteiligung innerer Organe wie Lunge, Herz und Leber moglich ist.

We report the third case of lipodystrophia centrifugalis abdominalis outside East Asia. A 4-year-old Caucasian girl developed an area of bluish erythema on the left side of the lower abdomen which spread centrifugally to the umbilical and inguinal areas with depression of the skin resulting from the loss of subcutaneous fat, surrounded by an erythematous border. This unusual skin disease was characterized by clinical and histological examination. Laboratory tests revealed a partial IgA deficiency, antinuclear antibodies and IgG antibodies against gliadin.

Idiopathic CD4+ lymphocytopenia is a rare disease without HIV infection or any other underlying immunodeficiency. Patients with this condition are predisposed to various opportunistic infections. We describe a 31-year-old woman with giant molluscum contagiosum disseminated over nearly the whole body. Immunologic analysis disclosed very low numbers of CD4+ lymphocytes (

Schnitzler's syndrome is a distinct disease entity characterized by the association of chronic urticaria, intermittent fever, arthralgia, elevated erythrocyte sedimentation rate and IgM macroglobulinaemia. We report a patient with the same symptoms, but a monoclonal IgG instead of IgM gammopathy. Histological examination of the urticarial lesions showed signs of mild leucocytoclastic vasculitis. Except for the different class of the monoclonal immunoglobulin, the clinical symptoms, laboratory findings and histology in this patient were identical with those in classical Schnitzler's syndrome. IgG and IgM paraproteins may be equivalent with regard to the putative pathophysiology of the disease process in Schnitzler's syndrome. We therefore suggest that the spectrum of Schnitzler's syndrome is expanded to include patients with chronic urticaria and monoclonal IgG gammopathy, as a closely related variant.

Summary Background In recent years it has been controversially discussed in the literature if smoking is associated with the activity of cutaneous lupus erythematosus (CLE) and the efficacy of antimalarial agents. Objectives To investigate the influence of smoking on disease severity and antimalarial treatment in patients with CLE using the Core Set Questionnaire of the European Society of Cutaneous Lupus Erythematosus (EUSCLE). Methods A total of 1002 patients (768 female, 234 male) with different CLE subtypes were included in this cross-sectional study, which was performed in 14 different countries. Smoking behaviour was assessed by the EUSCLE Core Set Questionnaire in 838 patients and statistically analysed using an SPSS database. The results were correlated with the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) and the efficacy of antimalarial treatment. Results A high percentage (87·2%) of the 499 patients with CLE, who have ever smoked, had already smoked at the date of their first diagnosis. Patients with intermittent CLE have ever smoked significantly more often than patients with subacute CLE (P < 0·05) and chronic CLE (P < 0·05). The total CLASI activity and damage score of patients with CLE was 6·6 ± 7·1 and 2·6 ± 4·3, respectively, and was higher in patients who have ever smoked than in nonsmokers. Antimalarial treatment was successful in 84·3% of cases, with a significantly higher efficacy in nonsmokers than in patients with CLE who have ever smoked (P < 0·05). Conclusions This analysis of a multicentre study population of 838 patients with CLE assessed by the EUSCLE Core Set Questionnaire confirms that smoking negatively influences CLE disease severity and the efficacy of antimalarial treatment. What's already known about this topic? The influence of smoking on disease severity in patients with cutaneous lupus erythematosus (CLE) and the efficacy of antimalarial treatment is still being controversially discussed in literature. What does this study add? The present analysis of a study population of 838 patients with CLE suggests that smoking is a risk factor for the disease, in particular for intermittent CLE. The results confirm that there is a negative influence of smoking on disease severity and that the efficacy of the antimalarials hydroxychloroquine and chloroquine is affected by smoking.

We report two patients with low-grade malignant primary cutaneous B cell lymphoma in association with Borrelia burgdorferi infection. Extracutaneous manifestations were ruled out by standard staging procedures. Infection with Borrelia burgdorferi was confirmed by cultivation from lesional skin in both patients. In the first patient skin lesions cleared completely after pulse therapy with cefotaxime, whereas in the second patient antibiotic treatment failed. In this patient, however, skin lesions completely cleared after intralesional injection of interferon alfa-2a. Antibiotic treatment or intralesional injection of interferon alfa-2a should be considered as a first-line treatment of Borrelia burgdorferi —associated primary cutaneous B cell lymphoma before more aggressive conventional therapeutic modalities (e.g., radiation therapy) are applied.

A 38-year-old HIV-positive man had several attacks of high fever associated with extensive perspiration over a 10-week period. Simultaneously, he developed molluscum contagiosum-like papules and an erythematous plaque on the face, ulcerated papules on both shoulders and buttocks and subcutaneous nodules on the arms. Histological examination of biopsy specimens revealed a diffuse, histiocytic infiltrate with abundant rod-shaped bacteria. Mycobacterium avium complex was cultured from the tissue and Mycobacterium avium complex DNA was detected by the polymerase chain reaction. The diagnosis of disseminated disease was additionally confirmed by culturing Mycobacterium avium complex from blood, sputum and stool. The skin lesions healed completely within 10 weeks by a multiagent as the patient was treated with a drug therapy. We describe the differential diagnosis, diagnostic procedures and therapy of disseminated infection with Mycobacterium avium complex.

Die Papillomatosis confluens et reticularis (PCR) ist eine seltene Erkrankung unklarer Atiopathogenese. Neuere elektronenmikroskopische Untersuchungen stutzen die Vermutung, das eine Keratinisierungsstorung vorliegt. Anhand unseres Falles konnten wir diese Befunde allerdings nicht bestatigen. Die PCR ist ausgesprochen therapieresistent. Wir behandelten einen 19jahrigen Patienten mit klinisch und histologisch typischer PCR systemisch mit Minocyclin. Innerhalb weniger Wochen heilten die Effloreszenzen vollstandig ab. Ein 7 Monate spater auftretendes leichtes Rezidiv konnte durch einen zweiten Behandlungszyklus schnell und erfolgreich behandelt werden. Der Patient ist jetzt bereits 12 Monate nach Absetzen der Therapie erscheinungsfrei. Zur Behandlung der PCR sollte Minocyclin wegen seiner geringeren Nebenwirkungen systemischen Retinoiden vorgezogen werden.

The aim of this prospective, cross-sectional, multicentre study performed by the European Society of Cutaneous Lupus Erythematosus (EUSCLE) was to investigate different therapeutic strategies and their efficacies in cutaneous lupus erythematosus (CLE) throughout Europe. Using the EUSCLE Core Set Questionnaire, topical and systemic treatment options were analysed in a total of 1002 patients (768 females and 234 males) with different CLE subtypes. The data were correlated with the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) and the criteria of the American College of Rheumatology (ACR) for the classification of systemic lupus erythematosus. Sunscreens were applied by 84.0% of the study cohort and showed a high efficacy in preventing skin lesions in all disease subtypes, correlating with a lower CLASI activity score. Topical steroids were used in 81.5% of the patients, with an efficacy of 88.4%, whereas calcineurin inhibitors were applied in 16.4% of the study population and showed an efficacy of 61.7%. Systemic agents including antimalarials and several immunomodulating/-suppressive drugs, such as systemic steroids and methotrexate, were applied in 84.4% of the 1002 patients. The CLASI activity and damage score was higher in treated CLE patients compared to untreated patients, regardless of therapy with topical or systemic agents. In summary, preventive and therapeutic strategies of 1002 patients with different subtypes of CLE were analysed in this prospective, multicentre, Europe-wide study. Sunscreens were confirmed to be successful as preventive agents, and topical steroids showed a high efficacy, whereas antimalarials were used as first-line systemic treatment.

Temporary hair loss is well accepted as a possible result of psoriatic plaques. On the other hand, it is still a controversial issue whether psoriasis can cause scarring alopecia. The following report presents a 38-year-old woman who had been suffering from progressive hair loss from chronic psoriatic plaques of the scalp for some years. Clinical examination revealed an area of scarring alopecia in association with typical features of psoriasis. Histology showed a cordlike fibrosis replacing former hair follicles, a perivascular lymphohistiocytic infiltrate in the upper dermis occasionally invading the follicular epithelium, and characteristic features of psoriasis of the scalp. The clinical course and the lack of evidence for any other causes of scarring alopecia suggest an aetiopathogenetic link between psoriasis and scarring alopecia. Knowledge of this relationship appears to be of practical significance, since efficient antipsoriatic therapy can stop hair loss and thus may be able to prevent scarring.

Twenty-nine cases of Langerhans cell histiocytosis (LCH), non-Langerhans cell histiocytoses (N-LCH), non-infectious granulomas, and fibroblast-related lesions were examined with a panel of monoclonal and polyclonal antibodies on freshly frozen tissue sections to characterize the macrophage phenotype of N-LCH syndromes. MS-1 high molecular weight extracellular protein, specific for sinusoidal endothelial cells and dendritic perivascular macrophages in normal human organs, was expressed by N-LCH cells but was not found in LCH cells, epithelioid cells in sarcoidosis, or palisading histiocytes in granuloma annulare. The subcellular location of MS-1 protein, i.e., cytoplasmic vs. peripheral/extracellular, allowed discrimination of small and large (foamy or multinucleated) N-LCH cells. MS-1-positive cells, which were found intermingled in cellular dermatofibromas but not in fibrous dermatofibromas, differed from MS-1-positive N-LCH cells by their dendritic morphology, and thus rather resembled their normal dermal counterparts. A preserved functional relationship of these two MS-1-positive cell types was indicated by the fact that N-LCH and cellular dermatofibromas were the only lesions found to be highly vascularized. As expected, CD1a showed high specificity for LCH, while CD34 was predominantly expressed by fibroblast-related lesions; in cellular dermatofibromas, CD34 and MS-1 expression partially overlapped. The other antigens tested showed non-specific or overlapping patterns of expression. In conclusion, assessment of MS-1 protein expression (in addition to assessment of CD1a and CD34) promises to be of diagnostic value in the discrimination of N-LCH from related skin disorders, and it may indicate a common differentiative pathway for most N-LCH disease entities.

In patients with cutaneous lupus erythematosus (CLE) and mild skin involvement, local therapy consisting of topically applied pharmacological agents, e.g., topical/intralesional steroids, may be sufficient. Recent reports have also shown efficacy of topical calcineurin inhibitors in patients with CLE, particularly on the face. Special attention receives consistent sun protection through photoresistant clothing and application of light-shielding substances with highly potent chemical or physical UVA- and UVB-protective filters. These substances should be applied in sufficient amount (ca. 2 mg/cm2) at least 20—30 minutes before sun exposure in order to avoid induction and exacerbation of cutaneous lesions. The mainstay of treatment for disfiguring and widespread skin manifestations in patients with CLE, irrespective of the subtype of the disease, is antimalarial agents. Our understanding of the use of combinations of antimalarials and proper dosing according to the ideal bodyweight limits problems with toxicity. Further therapies, such as methotrexate, or retinoids, dapsone, mycophenolate mofetil, and thalidomide in selected cases, can be helpful for patients with resistant disease; however, side effects need to be taken into consideration. Recent advances in biotechnology resulted in the development of novel systemic agents, but randomized controlled trials are necessary for the approval of new therapeutic strategies in CLE. Lupus (2010) 19, 1125—1136.

Cutaneous lupus erythematosus (CLE) is a heterogeneous autoimmune disease involving well-defined skin lesions that can be categorized as acute CLE (ACLE), subacute CLE (SCLE), chronic CLE (CCLE), or intermittent CLE (ICLE). It is commonly accepted that ultraviolet (UV) exposure can induce and exacerbate skin lesions in patients with certain subtypes of CLE. Phototesting with UVA and UVB irradiation using a standardized protocol has proven to be a reliable model to study photosensitivity in CLE and to analyse the underlying pathomechanisms of the disease. In addition to UV-mediated induction of apoptosis, the molecular and cellular factors that may underlie the abnormal long-lasting photoreactivity in CLE include mediators of inflammation such as cytokines and chemokines, inducible nitric oxide (NO) synthase (iNOS), and cellular adhesion molecules. The photosensitivity associated with CLE requires education of the patient about avoidance of excessive sun exposure, continuous photoprotection through physical measures such as protective clothing, and daily application of broad-spectrum sunscreens. Novel approaches to UV-protection, such as alpha-MSH or thymidine dinucleotides, might also have an impact on photosensitivity in patients with CLE. In this review, we summarize the current knowledge about photosensitivity in patients with CLE, including an overview of standardized phototesting procedures, possible molecular pathomechanisms, and photoprotection. Lupus (2010) 19, 1036—1046.

The aim of this study was to determine whether the Core Set Questionnaire developed recently by the European Society of Cutaneous Lupus Erythematosus (EUSCLE) is a useful tool to evaluate clinical features and therapeutic strategies in cutaneous lupus erythematosus. Disease characteristics were analysed in 50 patients with different subtypes of cutaneous lupus erythematosus from two European centres (Germany and Sweden). Mean age at onset of disease was 42.0 +/- 13.3 years (range: 7-69 years) and this differed significantly between the cutaneous lupus erythematosus subtypes. Moreover, 22 (44.0%) of the patients with cutaneous lupus erythematosus fulfilled four or more of the American College of Rheumatology (ACR) criteria; however, only 7 (14.0%) had severe systemic organ manifestations, such as kidney involvement. The analysis of serological features, such as antinuclear antibodies, revealed further significant differences between the cutaneous lupus erythematosus subtypes. In conclusion, the EUSCLE Core Set Questionnaire provides a useful tool for standardized collection and statistical analysis of data on cutaneous lupus erythematosus in clinical practice.

In the first part of the review, topical agents and first-line systemic treatment options for cutaneous lupus erythematosus were discussed whereas in the second part, recent information on efficacy, dosage, and side effects for further systemic treatment options are described in detail. In contrast to other immunosuppressive agents, such as azathioprine, cyclophosphamide, and cyclosporine, methotrexate has recently received more attention in the treatment of the disease. Further second-line treatment includes retinoids, dapsone, and mycophenolate mofetil. Because of severe side effects or high costs, other agents, such as thalidomide or high-dose intravenous immunoglobulins, are reserved for severe recalcitrant CLE. Biologics, ie, rituximab, have been used to treat systemic lupus erythematosus; however, in CLE, most biologics have only been applied in single cases. In addition to successful treatment, induction of CLE subtypes by biologics has been reported. In conclusion, many treatment options exist for CLE, but not many are supported by evidence from randomized controlled trials.