Mycophenolate mofetil is ineffective in the treatment of mucocutaneous Adamantiades-Beh?et's disease.

BACKGROUND: Cyclosporine A and azathioprine are effective on mucocutaneous lesions in Adamantiades-Beh?et's disease. Mycophenolate mofetil (MMF) is a drug resembling their activity but with comparably negligible adverse reactions. OBJECTIVE: A prospective clinical proof-of-principle study was conducted to investigate the effectiveness and toxicity of MMF in mucocutaneous Adamantiades-Beh?et's disease. METHODS: Thirty patients were to be treated with MMF 2 g/day p.o. for 6 months, in combination with prednisolone 30 mg/day p.o. during the first month of treatment. Inefficacy was followed by an increase in MMF dose to 3 g/day. The primary efficacy variable was the decrease in the disease activity index (DAI) according to a modified variant of the Iran Beh?et's Disease Dynamic Activity Measure system. RESULTS: The study was interrupted due to inefficacy of the compound after the intermediate evaluation of the first 6 patients (aged 37.0 +/- 7.7 years with disease duration of 10.0 +/- 8.9 years) as required by the ethical committee. Although an improvement of the DAI from 5.2 +/- 3.5 to 1.3 +/- 0.5 was found after the first month of combination treatment, withdrawal of prednisolone led to quick relapses with a new index increase (3.0 +/- 3.5). The treatment was discontinued in 3 patients after 3 months, in 2 patients after 4 months and in another one after 5 months due to deterioration of the disease. Introduction of interferon alpha(2a) (3 x 9 million IU 3x/week s.c.) in 3 patients decreased the activity index from 4.0 +/- 1.0 to 0.0 +/- 0.0. No adverse effects were detected under MMF treatment. CONCLUSION: MMF (2-3 g/day) is unable to control the signs of mucocutaneous Adamantiades-Beh?et's disease.     

Tratamiento de la dermatitis atópica grave del adulto con mofetil micofenolato en 8 pacientes

BackgroundAtopic dermatitis (AD) includes severe forms that can be refractory to various systemic treatments. Mycophenolate mofetil (MMF) has been found to be useful in patients with severe forms of AD and to have fewer side effects than long-term treatment with oral corticosteroids or cyclosporine.ObjectivesTo evaluate the efficacy and adverse effects of MMF in patients seen in our skin allergy unit with severe adult AD refractory to other systemic treatments.MethodsWe performed a retrospective study of 8 patients with severe adult AD treated with MMF, analyzing the baseline characteristics, previous treatments used by the patients, and the outcome and adverse effects of treatment with MMF.ResultsFive patients treated with MMF showed improvement in the fourth week of treatment. In addition, 5 of the 8 patients presented a clear, long-term improvement in their disease. Remission of AD occurred in 1 patient, making it possible to discontinue MMF; this patient remains stable with no relapses after 4 months without treatment. The other 4 patients continue on maintenance therapy. Three patients continued to have frequent acute outbreaks of AD despite treatment with MMF for 16 to 72 weeks. All patients tolerated the treatment and there were few adverse effects.ConclusionsMMF can be an effective option in selected patients with severe forms of atopic dermatitis. Although the response is not as rapid as with oral corticosteroids or cyclosporine, it can be used for maintenance treatment with good clinical control and few adverse effects.     

An evaluation of the usefulness of mycophenolate mofetil in pemphigus

BACKGROUND: Pemphigus is a group of autoimmune blistering diseases of the skin and/or mucous membranes requiring management with immunosuppressive therapy. The optimal therapeutic regimen would rapidly induce remission and maintain effectiveness with minimal adverse effects in the long term. OBJECTIVES: The present study describes our experience of the addition of mycophenolate mofetil (MMF) to prednisolone in the management of severe, refractory pemphigus. METHODS: Patients with active, refractory pemphigus were treated with MMF. Our series included 12 cases of pemphigus vulgaris, four cases of pemphigus foliaceous and one case of paraneoplastic pemphigus. All patients were monitored to assess disease control and mycophenolate toxicity. RESULTS: Of the 17 cases, MMF has been of benefit to 12. MMF was well tolerated and there were no treatment withdrawals because of safety concerns. CONCLUSIONS: We found that MMF permitted a reduction in prednisolone dosage without disease relapse.     

Treatment of pemphigus vulgaris and pemphigus foliaceus with mycophenolate mofetil

BACKGROUND: Mycophenolate mofetil is increasingly being used as a corticosteroid-sparing agent in immunosuppressive regimens. OBJECTIVE: To elucidate the effectiveness of mycophenolate as adjuvant therapy in the treatment of both pemphigus vulgaris and pemphigus foliaceus. DESIGN: Historical prospective study. SETTING: University hospital. PATIENTS: The study included 42 consecutive patients with pemphigus (31 with pemphigus vulgaris and 11 with pemphigus foliaceus) who had relapses during prednisone taper or had clinically significant adverse effects from previous drug therapy. RESULTS: Remission was achieved in 22 (71%) and 5 (45%) of patients with pemphigus vulgaris and pemphigus foliaceus, respectively. Partial remission was achieved in 1 (3%) and 4 (36%), respectively. The median time to achieve complete remission was 9 months (range, 1-13 months). The treatment was administered for a median of 22 months, and the median follow-up period was 22 months. Seventy-seven percent of patients had no adverse effect. Two patients had side effects severe enough to necessitate discontinuation of treatment, one because of symptomatic but reversible neutropenia and the other because of nausea. CONCLUSION: Mycophenolate is an effective and safe adjuvant in the treatment of both pemphigus vulgaris and pemphigus foliaceus.     

Mycophenolate mofetil therapy for moderate to severe atopic dermatitis

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory disease of the skin that can be refractory to topical and systemic corticosteroids, phototherapy, topical immunomodulators and systemic immunosuppressive drugs. Recent studies have shown promise for the use of mycophenolate mofetil (MMF) to treat recalcitrant AD. AIM: To assess the effectiveness and adverse effects of MMF used for moderate to severe AD in a university outpatient dermatology clinic. METHODS: A retrospective chart review of 20 patient charts was conducted for patient age, gender, duration of disease, prior therapies, concomitant therapy, clinical response and adverse side-effects. RESULTS: Of the 20 patients, 17 improved within 4 weeks of starting MMF therapy. Ten patients had disease remission and were subsequently able to discontinue MMF. Seven attained satisfactory control of their AD using MMF as maintenance therapy. Overall, MMF was well tolerated, with mild headaches, gastrointestinal complaints and fatigue as the commonest side-effects. During therapy, herpes zoster developed in four patients, Staphylococcus aureus cutaneous infections in two, and herpes simplex in one. One patient discontinued MMF because of insufficient control of pruritus. CONCLUSION: MMF can be rapidly effective and well tolerated in patients with moderate to severe AD resistant to conventional therapies. The limitations of this retrospective study include no control group and a lack of a standardized scoring index to assess improvement, and the concomitant use of adjuvant therapies makes the contribution of MMF alone difficult to assess. Larger controlled studies are needed.     

Cicatricial pemphigoid: treatment with mycophenolate mofetil

BACKGROUND: The severity of cicatricial pemphigoid (CP) varies. First-intent treatment of mild or moderate cases is dapsone. In life or sight-threatening cases, intravenous cyclophosphamide pulses are efficient but may have digestive side effects and imply repeated hospitalizations. Mycophenolate mofetil (MMF) is an oral and well tolerated immunosuppressant agent which has proved its efficacy in pemphigus and some bullous pemphigoid. In CP, encouraging case reports have been previously published. We report herein a retrospective study about 14 patients who have received MMF since 2000. PATIENTS AND METHODS: There were 5 men and 9 women, with a mean age of 69 years. MMF was introduced in 3 different clinical situations: immediately in relay to cyclophosphamide in 7 patients with severe CP (group I); in case of a mild-severe relapse at distance from with dranal of cyclophosphamide in 3 patients (group II); as first-intent immunosuppressant agent in 4 patients whose disease was not under control with high-dose dapsone, but not life - or sight-threatening (group III). In all these patients, the disease was invalidating and not controlled by dapsone +/- sulfasalazine, but did not threaten life or sight. The aim was to achieve satisfying control of the disease with an oral and well tolerated immunosuppressant agent, and to maintain good quality of life. The dose of MMF was 1.5 or 2 g per day. The criteria of MMF efficacy was the healing of previous lesions and the absence of new progressive lesions. RESULTS: MMF was efficient in obtaining or maintaining a good control of the disease in 10/14 patients, as long as the underlying treatment with dapsone (2 mg/kg/d) was maintained. In 7/10 cases, it was possible to decrease the dapsone dose in order to improve hematological tolerance. In the 3 other cases, a relapse occurred when the dose of dapsone was decreased. MMF was inefficient in controling the disease in 4/14 patients (29 p. 100). Clinical and biological tolerance of MMF was good in 13/14 patients. DISCUSSION: In this series, MMF was proposed to heterogenous patients, who presented at that time a mild-moderate disease and for whom we wanted in improve the quality of life. MMF seems to be an interesting drug, capable of obtaining or maintaining satisfactory control of the disease and permitting the decrease of dapsone doses in some mild-severe CP. However MMF must not replace cyclophosphamide in severe sight or life-threatening forms of CP.     

Brazilian pemphigus foliaceus autoantibodies are pathogenic to BALB/c mice by passive transfer

Brazilian pemphigus foliaceus (fogo selvagem) is a cutaneous blistering disease endemic to certain areas of South America that has distinctive epidemiologic features suggestive of an infectious disease transmitted by an insect vector. Patients with the disease have antiepithelial autoantibodies, both circulating in the serum and bound to lesional epidermis. In order to examine the possible pathogenic role of these autoantibodies, IgG from the sera of these patients was purified and injected into the peritoneum of neonatal BALB/c mice. Thirty-four of 46 mice (74%) receiving parenteral IgG fractions from these patients developed cutaneous lesions that were identical to the human disease by clinical, histologic, immunologic, and ultrastructural criteria. High-titer Brazilian pemphigus foliaceus sera produced lesions more consistently and rapidly than low-titer sera. When injections were discontinued, new lesions ceased to appear and old lesions resolved. The extent of disease correlated with the titer of human antiepithelial antibodies detected in the mouse serum (z less than 0.01). Similar concentrations of IgG fractions obtained from sera of unaffected Brazilians living in endemic areas and from American donors did not induce disease when injected into littermates. These results establish that the antiepithelial autoantibodies play an important role in the pathogenesis of the cutaneous lesions in Brazilian pemphigus foliaceus.     

Comparative study of pemphigus vulgaris and pemphigus foliaceus in Singapore

This is a retrospective study of all patients diagnosed to have pemphigus in our centre over a 3 year period. The case records of all patients with pemphigus from January 1995 to December 1997 were analysed. Fifty patients were diagnosed to have pemphigus during the study period. The diagnoses were pemphigus vulgaris in 31 patients, pemphigus foliaceus in 16, paraneoplastic pemphigus in two and IgA pemphigus in one. The average titre of anti-intercellular antibodies in patients with pemphigus vulgaris (1:96) was higher than the titre in patients with pemphigus foliaceus (1:69). The average initial dose of prednisolone required for disease control in patients with pemphigus vulgaris (62 mg/day) was significantly higher than that required for patients with pemphigus foliaceus (44 mg/day). In our study population, pemphigus vulgaris is a more severe and chronic disease than pemphigus foliaceus, as reflected in the higher titre of anti-intercellular antibodies, higher dose of systemic corticosteroids required for control of the disease, the longer duration to achieve complete remission and longer follow-up period.     

An experience for ELISA for desmoglein 1, suggesting a possible diagnostic help to determine the initial therapy for pemphigus foliaceus

Pemphigus foliaceus (PF) is an autoimmune skin disease in which loss of adhesion between keratinocytes (i.e., acantholysis) in the granular cell layers appears to be mediated by the binding of autoantibodies against desmoglein (Dsg) 1. Although it has been suggested that the activity of the disease is rather correlated with the titer of the antibody, there are still no precise studies on the relationships between the disease activity and the titers of autoantibody against Dsg1 by using ELISA. In this study, we performed ELISA using recombinant Dsg1 (rDsg1) as antigen on 8 patients with pemphigus foliaceus in order to examine the reliability of this test for monitoring disease severity. The resultant index values of ELISA, which were defined by the formula: (OD of tested serum - OD of negative control)/(OD of positive control - OD of negative control) X 100, ranged from 16 to 264 compared with 6.41 of cutoff index value for normal sera. A patient with an index value of 213 had severe widespread erosions with erythema and required pulse therapy of methylpredonisolone (1,000 mg/day for 3 days). A patient with an index value of 111 had a moderate severity and was successfully treated with an initial dose of 30 mg/day (0.64 mg/kg) of predonisolone. The mildest patient with an index value of 16 was controlled with only topical application of 0.05% betamethasone ointment twice a day. These results suggest that ELISA index values for rDsg1 will provide a promising tool for monitoring the disease severity and for determining the initial therapy for pemphigus foliaceus.     

Topical mometasone furoate and betamethasone-17-valerate decrease collagen synthesis to a similar extent in human skin in vivo

Topical corticosteroids are used extensively to treat inflammatory skin diseases. Long-term use, however, may be associated with adverse effects such as skin atrophy. New steroids have been developed with the objective of increasing efficacy and reducing the incidence of adverse effects. Mometasone furoate (MMF) is one of these new derivatives. The aim of our study was to compare the effects of MMF and betamethasone-17-valerate (BM-17-valerate) on collagen synthesis in human skin in vivo. Fifteen healthy male volunteers applied MMF, BM-17-valerate and vehicle for 1 week to different areas of abdominal skin. Suction blisters were raised on these areas, and a control site, and procollagen propeptide (PICP, PINP, PIIINP) levels in the suction blister fluid were measured by radioimmunoassay. Skin thickness was measured ultrasonically by Dermascan A at the end of the treatment period. The levels of the three propeptides in suction blister fluid were reduced to a similar extent by MMF and BM-17-valerate. The 1-week treatment period had no detectable influence on skin thickness. We conclude that MMF and BM-17-valerate decrease collagen synthesis to the same extent in human skin in vivo.     

Treatment of atopic eczema with oral mycophenolate mofetil

BACKGROUND: Activated T and B lymphocytes are the predominant inflammatory cells in atopic eczema (AE) lesions. Mycophenolic acid, the active form of mycophenolate mofetil (MMF), blocks the proliferative responses of T and B lymphocytes. OBJECTIVES: In this pilot study, we examined the efficacy of MMF (CellCept(R), Hoffman La Roche, Grenzach-Wyhlen, Germany) in severe AE. METHODS: Ten patients with severe AE (severity index > 50) according to the Severity Scoring of Atopic Dermatitis (SCORAD) index were treated with oral MMF at an initial dose of 1 g daily during the first week and 2 g daily for a further 11 weeks. Laboratory examination including full blood count, lymphocyte subset analysis, serum immunoglobulins (IgE, IgG, IgM, IgA), total bilirubin, alkaline phosphatase, aminotransferases, lactate dehydrogenase and creatinine was performed every 2 weeks. Additionally, interleukin (IL)-10 and interferon (IFN)-gamma in serum were measured. RESULTS: None of the 10 patients who received MMF discontinued the trial because of lack of efficacy or adverse events. Compared with the baseline, the median scores for disease severity (SCORAD index) improved by 68% during treatment with MMF. The median serum IgE level decreased significantly, from 10,300 kU L-1 before treatment to 7830 kU L-1 after 12 weeks. MMF induced a significant increase in the T-helper (Th)-1-related cytokine IFN-gamma and a significant decrease in IL-10, mainly produced by Th2 cells. CONCLUSIONS: The present study demonstrates that oral MMF at a dose of 2 g daily is an effective, safe and well-tolerated immunosuppressive therapy for severe AE in adults.     

Anti-desmoglein 1 antibodies in healthy related and unrelated subjects and patients with pemphigus foliaceus in endemic and non-endemic areas from Tunisia

Background  Pemphigus foliaceus is an autoimmune blistering skin disease characterized by the production of pathogenic IgG autoantibodies directed against desmoglein 1.
Aim  To determine the prevalence of anti-desmoglein 1 antibodies in healthy subjects and their distribution in the different regions of Tunisia and to better identify endemic areas of pemphigus foliaceus.
Methods  We tested, by enzyme-linked immunoserbent assay, sera of 270 normal subjects recruited from different Tunisian areas and 203 related healthy relatives to 90 Tunisian pemphigus foliaceus patients.
Results  Seventy-six patients (84.4%), 20 healthy controls (7.4%), and 32 relatives (15.76%) had anti-desmoglein 1 antibodies. In southern regions where pemphigus foliaceus is associated with a significant sex ratio imbalance (9 female : 1 male in the south vs. 2.3 : 1 in the north) and a lower mean age of disease onset (33.5 in the south vs. 45 years in the north), a higher prevalence of anti-desmoglein 1 antibodies in healthy controls was observed (9.23% vs. 5.71% in the north). Interestingly, the highest prevalence of anti-desmoglein 1 antibodies in healthy relatives (up to 22%) was observed in the most rural southern localities. More than half anti-desmoglein 1–positive healthy controls were living in rural conditions with farming as occupation, which suggests that this activity may expose the subjects to particular environmental conditions.
Conclusion  These results show that the endemic features of Tunisian pemphigus foliaceus are focused in these southern areas more than in other areas and that both environmental and genetic factors contribute to the disease.

Conflicts of interest

None declared.     

Common human leukocyte antigen alleles in pemphigus vulgaris and pemphigus foliaceus Italian patients.

Pemphigus refers to a group of autoimmune blistering skin diseases, mainly identified as pemphigus vulgaris and pemphigus foliaceus, both characterized by the presence of autoantibodies against keratinocyte adhesion molecules, leading to loss of cell-cell adhesion with consequent blister formation. Pemphigus vulgaris is reported to be associated with human leukocyte antigen DR4 and/or DR6 whereas no data are available on pemphigus foliaceus, except for the endemic Brazilian form (fogo selvagem), which is reported to be associated with DR1 and DR4. We here report human leukocyte antigen molecular typing on a total of 87 patients, 61 with pemphigus vulgaris and 26 with pemphigus foliaceus, versus 128 healthy matched controls. Generic typing showed an increase of DRB1*04 and DRB1*14 and a decrease of DRB1*07 in both pemphigus vulgaris and pemphigus foliaceus patients. Molecular subtyping of DR4+ and DR14+ subjects showed a highly significant association between the DRB1*1401 and both pemphigus vulgaris (p < 0.0001) and pemphigus foliaceus patients (p < 0.0001) together with a significant increase of the linked DQB1*0503 (pemphigus vulgaris p < 0.0001; pemphigus foliaceus p < 0.0001). Moreover, whereas the association between DRB1*0402 and pemphigus vulgaris (p < 0.0001) has been confirmed, no significant association between a specific allele of the DR4 group and pemphigus foliaceus, has been found. Therefore, at least in Italian patients, pemphigus vulgaris and pemphigus foliaceus share DRB1*1401 and DQB1*0503, as susceptible human leukocyte antigen alleles, whereas DRB1*0402 is only found associated with pemphigus vulgaris. The observation that both diseases, pemphigus vulgaris and pemphigus foliaceus, carry the same susceptible human leukocyte antigen alleles has been interpreted as a common genetic background predisposing to pemphigus as, like in other autoimmune disorders, it is not sufficient to explain the onset of the disease on the basis of the sole aforementioned alleles. Other linked genes and/or environmental factors should play a facilitating role in the outbreak of pemphigus, either pemphigus vulgaris or pemphigus foliaceus.     

Mycophenolate mofetil as adjuvant in pemphigus vulgaris

Pemphigus vulgaris (PV) is a life threatening autoimmune blistering disease of skin and mucous membranes. Advent of systemic steroids has greatly reduced the mortality rate. However, steroids and adjuvant immunosuppressive therapy are nowadays frequent contributory agents of morbidity and mortality of PV. Mycophenolate mofetil (MMF) has been reported to be an effective adjuvant to systemic steroids. It helps in increasing the immunosuppressive effect and minimizing the toxicities by steroid sparing effect. However, its efficacy in refractory cases of PV is not well documented. The lowest possible dose with satisfactory therapeutic efficacy and least side effects is known. We used MMF 1 g/day and systemic steroids in 3 Indian patients with pemphigus vulgaris who were resistant to systemic steroid monotherapy or combination treatment with azathioprine. In our experience, MMF offers an effective adjuvant with minimal side-effects in the treatment of resistant PV.     

Drug-induced pemphigus: autoantibodies directed against the pemphigus antigen complexes are present in penicillamine and captopril-induced pemphigus

Pemphigus is an autoimmune blistering disease characterized by circulating autoantibodies directed against the keratinocyte cell surface. The two variants, pemphigus foliaceus and pemphigus vulgaris, can be distinguished at the molecular level by immunochemical studies. The large majority of patients with pemphigus develop the disease spontaneously; however, there is a small group of patients who develop pemphigus after treatment with certain medications, of which penicillamine and captopril are the best documented. Most patients with drug-induced pemphigus have circulating and/or tissue bound epidermal cell surface autoantibodies; however, the molecular specificity of these autoantibodies has not been studied. We performed immunoprecipitation studies utilizing extracts of 125I-labeled suction blister epidermis and the sera of three patients with drug-induced pemphigus foliaceus (two due to penicillamine and one due to captopril) and one patient with captopril-induced pemphigus vulgaris. We found that the three patients with drug-induced pemphigus foliaceus had circulating autoantibodies that are directed against the pemphigus foliaceus antigen complex and that the one patient with drug-induced pemphigus vulgaris had circulating autoantibodies that are directed against the pemphigus vulgaris antigen complex. This study demonstrates that autoantibodies from drug-induced pemphigus patients have the same antigenic specificity, on a molecular level, as do autoantibodies from other pemphigus patients.     

PEMPHIGUS IN EL SALVADOR

Of 23 patients with pemphigus seen between 1970 and 1977, 18 had foliaceus and five had vulgaris (ratio of 3.73:1). The characteristics of pemphigus foliaceus (age of onset, disease among sisters, presence of lesions resistant to corticotherapy) suggest Brazilian pemphigus foliaceus (fogo selvagem).     

Tunisian endemic pemphigus foliaceus is associated with the HLA-DR3 gene: anti-desmoglein 1 antibody-positive healthy subjects bear protective alleles

Background  Pemphigus foliaceus is an autoimmune blistering skin disease that partly results from genetic factors, especially human leucocyte antigen (HLA) class II genes.
Objectives  The aim of the study was to determine the HLA DR/DQ markers of susceptibility and protection in the Tunisian endemic form.
Methods  Genomic DNA from 90 patients with pemphigus foliaceus recruited from all parts of the country and matched by age, sex and geographical origin with 270 healthy individuals, was genotyped.
Results  Firstly, when the whole patient population was studied, DRB1*03 , DQB1*0302 and DRB1*04 alleles were significantly associated with the disease while a significant decrease of, in particular, DRB1*11 and DQB1*0301 was observed in patients compared with controls. DRB1*0301 was the dominant allele in DR3-positive patients and controls, while DRB1*0402 was found in 42% of DR4-positive patients. Secondly, when the HLA DR/DQ allele distribution was studied after dividing patients according to their geographical origin, the southern group, which consisted exclusively of patients with the endemic form of the disease, showed the same associations as the whole pemphigus foliaceus population, particularly with DRB1*03 . In the northern group, only the DRB1*04 and DQB1*0301 alleles were found to be associated. Interestingly, anti-desmoglein 1 antibody-positive healthy controls did not carry susceptibility alleles but, in contrast, most carried negatively associated alleles.
Conclusions  These observations indicate that a particular genetic background characterizes the Tunisian endemic form of pemphigus foliaceus and that HLA class II genes control the pathogenic properties of the autoimmune response rather than the initial breakage of B-cell tolerance.     

Prognostic factors for life expectancy in nonagenarians with nonmelanoma skin cancer: implications for selecting surgical candidates

BACKGROUND: Pemphigus foliaceus is a cutaneous, autoimmune, blistering disease comprising two major categories: endemic and sporadic. The endemic form, also known as fogo selvagem, primarily affects children and young adults in rural Brazil. In contrast, the sporadic form of pemphigus foliaceus is generally a disease of the middle-aged and elderly. Objective and methods: Because the sporadic form of pemphigus foliaceus rarely affects children, information specific to this unique group is lacking. We describe a 3-year-old boy with the disease and retrospectively review data from 28 past cases. RESULTS: In comparison to pediatric cases of pemphigus vulgaris, sporadic pemphigus foliaceus in children tends to follow a generally benign course of relatively short duration. However, long-term outcome studies are lacking. A pattern of skin lesions described as "arcuate," "circinate," or "polycyclic" appears to be a unique and specific presentation of this disease in children. Occasionally, as in our case, the diagnosis may prove difficult to establish by using routine histology or immunopathology. CONCLUSION: The commercial availability of antigen-specific techniques such as enzyme-linked immunosorbent assay for serum desmoglein 1 autoantibody should eliminate delay in diagnosis. Hydroxychloroquine may be another treatment option for those children with photodistributed lesions. Further experience and long-term outcome studies in children are needed to determine whether some medication side effects may outweigh the risks from the disease itself.     

Influence of monomethylfumarate on monocytic cytokine formation – explanation for adverse and therapeutic effects in psoriasis?

Although the effectiveness of systemic antipsoriatic treatment with fumaric acid esters has been proven, their mode of action is still not understood. Recent results indicate their potency in inducing cytokine production in stimulated T cells. Since monocytes and their cytokines are also considered to be of pathogenic importance in psoriasis, we investigated the effect of monomethylfumarate (MMF) on proinflammatory (TNF-α, IL-12) and antiinflammatory (IL-10, IL-1RA) cytokine production by peripheral blood mononuclear cells (PBMC) and separated monocytes. In 24-h PBMC cultures from both psoriatic patients ( n = 6–13) and healthy volunteers ( n = 7–9), MMF at 100 μ M induced secretion of TNF-α, IL-10, and IL-1RA. Kinetics of IL-10 protein and mRNA expression indicated de novo production. Moreover, MMF significantly augmented endotoxin-induced synthesis of TNF-α, IL-10 and IL-1RA. In contrast, no influence on IL-12 secretion was found. Similar effects of MMF in purified monocytes indicated these cells to be responsible for aberrant cytokine formation. Furthermore, enhanced expression of costimulatory molecules after MMF stimulation confirmed monocyte activation. Multiple restimulation with fumaric acid esters in vitro, however, and immunomonitoring in a patient during Fumaderm initial therapy suggested that initial monocyte activation is followed by subsequent deactivation associated with an antiinflammatory response. Our results may explain the well-known effects of therapy with fumaric acid esters. Thus, initial treatment is often accompanied by adverse effects which may be caused by MMF-induced TNF-α formation. The change in the IL-10/IL-12 balance as a result of elective induction of IL-10, however, may have antipsoriatic activity by diminishing type-1/proinflammatory cytokine overexpression and the antigen-presenting capacity of monocytes/macrophages, and by upregulation of IL-1RA. Received: 16 April 1997