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The CD40/CD40 ligand system is expressed in the cutaneous lesions of erythema multiforme and Stevens-Johnson syndrome/toxic epidermal necrolysis spectrum.

BACKGROUND: Erythema multiforme (EM) and Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) are determined by a dysregulation of cellular immunity. OBJECTIVES: To evaluate the effector role of cellular immunity and the involvement of the CD40/CD40 ligand (CD40L) system in the pathogenesis of EM and SJS/TEN. METHODS: Biopsy specimens from eight patients with EM and six with SJS/TEN were stained for immunohistochemical examination using the alkaline phosphatase/antialkaline phosphatase method. The monoclonal antibodies used included those to CD1a, CD4, CD8, CD40, CD40L, CD68, Fas, Fas ligand (FasL) and myeloperoxidase. RESULTS: The cellular infiltrate in both EM and SJS/TEN lesions was composed mainly of T lymphocytes and CD68+ macrophages. We also detected large amounts of neutrophils. Fas and FasL were very highly expressed in SJS and TEN, but weakly in EM. CD40 staining was strong in all tissue sections; there were numerous CD40L+ cells in SJS/TEN but much fewer in EM. CONCLUSIONS: Activated T lymphocytes and macrophages, but also neutrophils, are presumably the main triggers of mucocutaneous damage in the SJS/TEN disease spectrum. The Fas/FasL system is significantly expressed in SJS/TEN lesions, but not in EM, where this apoptotic pathway presumably does not play a pivotal role in the epidermal damage. We suggest that the CD40/CD40L system may represent an important pathway of induction of SJS/TEN lesions, while in EM it would contribute to the immunoinflammation only as a second-line mechanism.

Adult↗

Validation of a semiautomated method of minimal erythema dose testing for narrowband ultraviolet B phototherapy.

BACKGROUND: The most widely used method for establishing the minimal erythema dose (MED) before narrowband ultraviolet (UV) B phototherapy is time-consuming, inconvenient and may yield inconsistent results. OBJECTIVES: To assess the equivalence of MED assessment using a filtered xenon arc lamp UV source, a semiautomated MED tester, and a UV-opaque template method of MED determination with a panel of TL-01 311-nm UVB fluorescent tubes. Secondly, to gauge the current usage of MED testing, and the method used, in a large sample of U.K. phototherapy units. Thirdly, to assess variation in UV output of the semiautomated skin tester immediately after switching on to identify optimum warm-up time. Finally, to assess reproducibility of MED testing by assessing within-patient variability and interobserver variability of MED test results. METHODS: Sixty-five patients about to undergo UVB phototherapy had their MED determined using three different methods. Within each patient we compared the values of MED determined by a semiautomated Durham MED tester, a panel of narrowband UVB lamps with a UV-opaque template constructed by a phototherapist, and a 310-nm filtered xenon arc lamp with a liquid light guide. MED test results were assessed by clinical evaluation using a 6500 K colour temperature examination lamp. The output of the semiautomated MED tester was measured by spectroradiometer over a period of 20 min in order to identify the time to steady output. Reproducibility of MED testing with the semiautomated MED tester was carried out in 25 normal volunteers. All MEDs were assessed by at least two independent observers. A postal questionnaire was sent to 78 U.K. phototherapy units to assess routine practice concerning MED testing prior to narrowband UVB phototherapy. RESULTS: The semiautomated MED tester showed consistency with the panel method (r = 0.92, panel MED = -0.57 + 1.14 x Durham MED). The semiautomated MED tester produced a slightly lower MED result than the panel MED. Reproducibility tests showed high interobserver agreement (kappa value = 0.79), and high consistency for successive day testing (kappa value = 0.79). Questionnaires were returned from 67 of 78 phototherapy units (85%) and revealed that 19 units (28%) were routinely using MED testing prior to UVB therapy. CONCLUSIONS: This study has shown the Durham MED tester to be a convenient, valid and reproducible method for determining patient MED values prior to narrowband UVB phototherapy when used under carefully controlled lighting, by experienced observers.

Adolescent↗

Expression of cytokines and chemokine receptors in the cutaneous lesions of erythema multiforme and Stevens-Johnson syndrome/toxic epidermal necrolysis.

BACKGROUND: Erythema multiforme (EM) and Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) are caused by a dysregulation of cellular immunity. OBJECTIVES: To evaluate further the potential role of certain cytokines and chemokine receptors in cutaneous lesions of patients affected by EM and SJS/TEN and to establish whether such diseases are polarized preferentially towards a T-helper (Th) 1 or Th2 pattern. METHODS: Biopsy specimens from eight patients with EM, six with SJS/TEN and three healthy controls were stained for immunohistochemical examination using the alkaline phosphatase-antialkaline phosphatase method. The monoclonal antibodies used included those to tumour necrosis factor (TNF)-alpha, interferon (IFN)-gamma, interleukin (IL)-2, IL-5, IL-13, receptor 3 for C-C chemokines (CCR3), receptor 3 for C-x-C chemokines (CXCR3) and CXCR4. RESULTS: The SJS/TEN specimens showed significantly higher expression of all the cytokines and chemokine receptors (except CXCR3) tested than the EM specimens. Both lesional series showed significantly higher expression of all the receptors tested than the healthy control specimens, with the sole exception of a lower expression of CCR3 in EM specimens. Comparison between molecules associated with a Th1 or Th2 response revealed a predominance of Th1 response in EM and no significant imbalance between Th1 and Th2 in SJS/TEN. CONCLUSIONS: We have provided further evidence that TNF-alpha is strongly expressed in SJS/TEN lesions and therefore it may be involved in the epidermal necrosis featured in such diseases. IFN-gamma may play an important role both in EM and SJS/TEN. IL-2, IL-5 and IL-13 may contribute to the cutaneous immunoinflammation in these diseases. Chemokine receptors may be involved strongly in the recruitment of inflammatory cells in lesional skin. In our cases we found a sharp polarization towards a Th1 pattern in EM, while the SJS/TEN lesions showed a mixed Th1/Th2 pattern.

Adult↗

Episodic erythema gyratum repens with ichthyosis and palmoplantar hyperkeratosis without signs of internal malignancy.

Two patients with typical lesions of erythema gyratum repens, peripheral ichthyosis, palmoplantar hyperkeratosis and nail changes are described. A non-specific erythrodermic eruption of several weeks' duration had preceded the typical lesions. No signs of internal malignancy were found and the typical gyrate lesions disappeared within some weeks with full restitution of all skin lesions within 6-8 months.

Aged↗

Erythema multiforme-like eruptions associated with etretinate therapy.

Mucocutaneous side-effects from etretinate are common and are usually dose-dependent, whereas hypersensitivity drug eruptions are rare. Two patients are described in whom erythema multiforme-like eruptions appeared several days after oral intake of etretinate. In one patient etretinate rechallenge again produced the skin eruption. A brief review of the less common skin manifestations of etretinate therapy is provided.

Drug Eruptions↗

Multifocal fixed drug eruption mimicking erythema multiforme.

A 38-year-old woman presented with a widespread bullous eruption that recurred during menstruation. Skin biopsy suggested erythema multiforme. As she was receiving synthetic progesterones for dysmenorrhoea the diagnosis of an auto-immune progesterone dermatitis was considered. However, subsequent investigations confirmed the diagnosis to be a fixed drug eruption to mefenamic acid taken for dysmenorrhoea.

Adult↗

Erythema elevatum diutinum--an unusual association with ulcerative colitis.

We report the association of erythema elevatum diutinum (EED) with ulcerative colitis (UC). The patient, whose history included rheumatoid disease, diabetes mellitus (type I) and hypothyroidism developed EED during a severe acute exacerbation of UC which resolved following colectomy. To our knowledge this is the first report of such an association. Also of interest was the observation of Köebner phenomenon occurring at the sites where blood vessels were damaged.

Colitis, Ulcerative↗

Erythema elevatum diutinum: a clinicopathological study.

Erythema elevatum diutinum is a syndrome of vasculitis in which lesions, typically over the extensor surfaces, showed a mixed inflammatory infiltrate on biopsy. We describe a series of 13 patients. The most common association in our series was with hypergammaglobulinemia; both mono and polyclonal. Chronic infection, not streptococcal, was a less frequent finding although two of three patients had a positive reaction to the intradermal injection of streptococcal antigen. Dapsone remains the initial treatment of choice.

Adolescent↗

Infectious mononucleosis presenting as erythema multiforme.

Infectious mononucleosis is rarely associated with skin lesions. A 23-year-old woman with acute infectious mononucleosis who presented with moderately severe erythema multiforme is reported. The role of steroids in the management of this condition is briefly discussed.

Adult↗

Nodular cystic fat necrosis in a patient with erythema nodosum.

Nodular cystic fat necrosis shows a distinctive spectrum of clinical and histological features. Most of the lesions are mobile subcutaneous nodules in regions vulnerable to trauma, such as the elbows, knees, and shins. There have been no reports of an association with other conditions. The histology is characterized by encapsulated fat necrosis in which multiple, non-viable adipocytes are surrounded by condensed fibrous tissue. We report a case of early stage nodular cystic fat necrosis associated with erythema nodosum.

Adipose Tissue↗

Erythema elevatum diutinum in human immunodeficiency virus-infected patients--report of a case and review of the literature.

Erythema elevatum diutinum (EED) is a rare chronic disease of unknown origin, part of the spectrum of cutaneous leucocytoclastic vasculitis. A case of EED in a 32-year-old HIV-infected male patient, with no previous opportunistic infections and a CD4+ cell count of less than 200/mm3, is reported. Therapy with oral dapsone (100 mg/day for 15 days) resulted in clinical cure with no relapse after 6 months of follow-up. To our knowledge, only six cases of EED in HIV-positive patients have been reported to date. A brief review of these seven cases is described.

Adult↗

Dermatomyositis and flagellate erythema.

Flagellate erythema, described by Moulin in 1970 as reminiscent of the lesions produced by flogging and by other authors as zebra-like lesions, was noted first in association with bleomycin treatment, but later occasionally reported in relationship with dermatomyositis, mostly from Japan. It is characterized by linear, erythematous, cutaneous streaks, pruriginous or painful, arising on an oedematous background and disappearing spontaneously over several weeks. So far, fewer than five cases have been reported in association with dermatomyositis, but we now present a further one.

Back↗

Intestinal bypass syndrome presenting as erythema nodosum.

Intestinal bypass was a popular surgical procedure for morbid obesity resulting, on average, in a 50 kg weight loss. We describe a 66-year-old woman who underwent the procedure 12 years earlier and subsequently presented with recurrent episodes of erythema nodosum-like lesions. Further investigations revealed hyperoxaluria, renal failure, deficiency of fat-soluble vitamins (causing night blindness, osteomalacia and easy bruising) and anaemia. Antibiotics led to only temporary remission and, as with 24-30% of similar cases, she underwent surgical reversal to prevent the complications from worsening.

Aged↗

Association of C4B deficiency (C4B*Q0) with erythema nodosum in leprosy.

A considerable number of studies have postulated significant associations between susceptibility to the different clinical manifestations of leprosy and the MHC. In this investigation, the association between the MHC class III complement proteins C2, BF, C4A and C4B and leprosy in a patient population of Southern Brazil was studied. A total of 109 non-related leprosy patients was investigated; 73 presented with lepromatous leprosy (LL), 46 of them had the immunopathological reaction of erythema nodosum (ENL), the remaining 36 were tuberculoid, borderline and indeterminate leprosy (TIBL) patients. The control group included 172 healthy individuals matched with the patients according to their ethnic and geographical origin. C2, BF, C4A and C4B allotypes were determined by standard technologies including Western blots for C2 and C4 variant alleles with monoclonal and polyclonal antibodies. Non-expressed ('silent') C4 alleles in hemizygously deficient individuals were estimated semiquantitatively on the basis of the C4A and C4B isotype ratio and by the MASC ('minimal chi-square') method. The results showed a significantly elevated presence of the non-expressed C4B allele (C4B*Q0) in the LL and ENL patient groups in comparison with the controls. The most significant difference was observed in the ENL group when compared with the controls. In addition, all patients who were homozygously C4B-deficient had ENL, and most of them had the BF*F1 allele. The comparison between LL patients with and without ENL also showed a statistically significant difference in the presence of C4B*Q0, indicating that C4B deficiency itself is associated with ENL. The relative risk of LL patients with the C4B*Q0 allele suffering from ENL was 5.3 compared with LL patients without C4B*Q0. Since immune complexes (IC) are considered to be the pathogenic cause of ENL, our findings indicate that C4B deficiency may play an important role in the abnormal immune response against Mycobacterium leprae and in the lack of IC clearance, leading to ENL reactions. Individuals with this allele seem to be at a higher risk of developing pathological immune reactivity in lepromatous leprosy.

Adult↗