Effect of phototherapy and urocanic acid isomers on natural killer cell function.

Ultraviolet (UV) radiation suppresses a variety of immune responses but it is uncertain whether this action contributes to the effectiveness of phototherapy. Urocanic acid (UCA) has been proposed as a mediator of the immunologic effects of UV. On exposure the naturally occurring trans-isomer of UCA in the skin changes into the cis-isomer, which has been demonstrated to mimic many of the immunomodulatory effects of UV irradiation. Natural killer (NK) cells play an important role in several immunologic processes and published evidence indicates that their activity is altered by UV irradiation. To ascertain the effect on NK cells of phototherapy used in the treatment of psoriasis, modulation of NK activity in psoriatic patients undergoing broad-band UVB, narrow-band UVB, or psoralen plus (PUVA) regimens was examined. This was compared with NK cell activity in psoriatic patients treated with topical coal tar and in normal subjects receiving broad band UVB. The NK cell activity of psoriatic and normal subjects was the same over a wide range of effector to target cell ratios. Almost all patients undergoing phototherapy exhibited depressed NK cell activity during or after irradiation, although the timing of the depression varied between the lamps used and may be related to dose. However, patients treated with topical coal tar showed unchanged NK cell activity throughout the therapy. The effect of UCA isomers on NK cell activity in vitro was also determined. It was found that cis-UCA induced a dose-dependent suppression of NK cell activity in both patients and normal subjects, whereas trans-UCA had hardly any effect in either group. Thus it is possible that there may be a correlation between cis-UCA formation in the epidermis and the modulation of NK cell activity that occurs during phototherapy.

Major histocompatibility class II antigen expression on the surface of epidermal cells from normal and ultraviolet B irradiated subjects.

The influence of ultraviolet B irradiation in therapeutic doses on MHC II-positive epidermal cell numbers and their surface MHC II antigen expression was studied quantitatively using light microscopic immunoperoxidase and immunogold electron microscopic techniques. In multiple ultrathin sections through many MHC II-positive epidermal cells from five healthy subjects, prior to ultraviolet exposure, Langerhans cells and indeterminate cells were found to express similar densities of surface MHC II antigens, which were uniformly distributed over the cell surface. The variation in surface MHC II antigen expression on 97 dendritic epidermal cells from one subject was normally distributed. Following a 6-week course of ultraviolet B irradiation, in the same doses as those normally used for the treatment of psoriasis, MHC II-positive epidermal cell numbers were significantly reduced (mean decrease to 51% of the pre-UVB sample; p < 0.001 analysis of variance), but their surface MHC class II antigen density was significantly increased (p < 0.05 analysis of variance). No MHC II-negative Langerhans cells were detected in either the pre- or post-UVB samples.

Helicobacter pylori serology in patients with coeliac disease and dermatitis herpetiformis.

AIMS: To investigate whether Helicobacter pylori infection or autoimmune gastritis is responsible for the reported increase in gastric pathology and abnormalities of gastric function in patients with coeliac disease and dermatitis herpetiformis (DH). METHODS: Serum H pylori IgG antibodies were assayed by enzyme linked immunosorbent assay and intrinsic factor antibodies by radioimmunoassay in 99 patients with coeliac disease and 58 patients with dermatitis herpetiformis from two geographic areas. RESULTS: H pylori positivity in patients with coeliac disease and dermatitis herpetiformis increased with age, reaching 50% and 70%, respectively, in patients over 50 years. The percentage H pylori seropositivity in coeliac disease did not differ from the percentage positivity observed in 250 similarly aged blood donors from the same geographic area (Leeds). Seropositivity in patients with dermatitis herpetiformis was not significantly different from the level of positivity observed in 98 age matched patients without dermatitis herpetiformis attending the same Edinburgh dermatology clinic. Only one patient with coeliac disease had positive intrinsic factor antibodies. H pylori seropositivity in Edinburgh control subjects under 30 years of age (41.9%) was significantly higher (p less than 0.03) than in Leeds controls (18%) of corresponding age. An increasing prevalence of H pylori seropositivity with age in coeliac disease and dermatitis herpetiformis paralleled that of the control groups. CONCLUSIONS: Gastritis in coeliac disease and dermatitis herpetiformis is largely caused by H pylori infection at a level that is no different from that of the general population. Any increase in the prevalence of gastritis in these two diseases might be caused by lymphocytic gastritis rather than pernicious anaemia.

Lymphoproliferative responses in recrudescent orofacial herpetic infections.

The relationship between antibody (Ab) and lympho-proliferative responses to herpes simplex virus (HSV) and recrudescent orofacial HSV lesions were investigated in 65 patients. All had HSV-specific Ab and cell mediated immune responses (CMIR) demonstrated by ELISA and in vitro lymphoproliferation respectively. Thirteen control subjects were negative in both tests. Thirty-three patients were repeatedly investigated for 6-38 months during which time they suffered 1-8 recrudescences. HSV-induced lymphoproliferation was depressed during recrudescences, rose to a peak several weeks later, and declined slowly to a background level. However, ELISA titres and lymphoproliferative responses to Concanavalin A (Con A) were high throughout and circulating peripheral blood mononuclear cell (PBMC) subsets did not change. Depressed lymphoproliferative responses to HSV antigen (Ag) during recrudescences were enhanced by removal of CD8+ cells from PBMC using either a panning technique or cell sorting; reconstitution of CD8+ cells suppressed the HSV-specific lymphoproliferative response. CD8+ cell depletion affected neither HSV-induced lymphoproliferation recrudescence, nor lymphoproliferative responses to another Ag (PPD) during recrudescence. Depressed HSV-induced lymphoproliferation during recrudescences might thus be due to CD8+ suppressor T cell (Ts) function rather than low numbers of circulating lymphocytes. Suppression or delay of normal CMIR to asymptomatic recurrent epidermal HSV infection by Ts might allow development of recrudescent HSV lesions.

Sweet's syndrome followed by acute myelomonocytic leukaemia: the need for follow-up.

We describe a patient who developed Sweet's syndrome, carefully investigated, one year before an acute myelomonocytic leukaemia developed. Such patients need to be followed up for at least five years before this possible association can be disproved.

Ear presentation of Lyme borreliosis in a child.

OBJECTIVE: This case report aims to raise awareness amongst clinicians of ear presentation of cutaneous borrelia. CASE REPORT: We report a recent case of borrelia lymphocytoma cutis benigna in a child presenting with unilateral earlobe swelling, who was otherwise well. A review of the English language literature, including management of the disease, is also presented. CONCLUSION: This case highlights the fact that borrelia lymphocytoma should be included in the differential diagnosis of a persistent, unilateral, inflamed, swollen earlobe in an otherwise healthy child.

A trial of 1% minoxidil used topically for severe alopecia areata.

Fifty patients with extensive alopecia areata took part in a prolonged double blind trial to compare the effect of 1% minoxidil in unguentum merck with that of unguentum merck alone. There was no significant difference between the hair growth of patients treated with the placebo or with the active compound.

Sweet's syndrome and non-Hodgkin's lymphoma: the first report of this association.

A 58-year-old woman developed Sweet's syndrome one week after a flu-like illness. She was later found to have a centrocytic/centroblastic non-Hodgkins lymphoma. Six courses of chemotherapy were given during which the lesions of Sweet's syndrome resolved completely. As far as we are aware this is the first report of the association of Sweet's syndrome with a lymphoma.

The effect of UV therapy on immune function in patients with psoriasis.

Ultraviolet radiation (UVR) is known to suppress some cell-mediated immune responses to antigens encountered during or soon after exposure. Phototherapy is widely used in psoriasis, and this study was undertaken to monitor changes in a range of immunological parameters during standard courses of treatment, with the aim of ascertaining whether such modulations contribute to the effectiveness of therapy. The responses of 17 patients with psoriasis undergoing UVB therapy, and four receiving PUVA therapy, were compared with 15 patients receiving coal tar treatment and four normal subjects undergoing UVB irradiation. In each case, samples were taken before starting therapy, after 4 weeks of therapy, and 4 weeks after completion of treatment. Serum immunoglobulin isotypes and complement components were within normal ranges in most of the psoriasis patients, and remained unchanged throughout therapy. Similarly, percentages of subsets of peripheral blood mononuclear cells (PBMC) were normal, and were unaltered by treatment. Patients who were already infected with herpes simplex virus (HSV), as demonstrated by a positive lymphoproliferation test in vitro, were monitored for asymptomatic HSV shedding and HSV recrudescences during therapy. There was little evidence that phototherapy caused reactivation of the virus. No significant alteration in lymphoproliferative response to HSV and to the mitogen concanavalin A was observed during therapy. Epidermal cells and blood adherent cells were used to present HSV to PBMC, depleted of adherent cells and enriched for T cells, in a lymphoproliferative assay. The functional antigen-presenting ability of adherent cells remained unchanged throughout therapy, whereas that of epidermal cells was suppressed during UVB irradiation and recovered, in most instances, after UVB therapy had been completed. The epidermis of patients with psoriasis contained about three times the quantity of urocanic acid (UCA) of normal subjects, whereas the UCA concentration in suction blister fluid did not differ between the two groups. During UVB irradiation, the percentage of cis-UCA rose in both the epidermis and suction blister fluid of all subjects, and it remained elevated in the blister fluid after therapy had finished. Tumour necrosis factor-alpha was measured in suction blister fluid, and its concentration did not alter consistently as a result of therapy. Whether any of the immunological parameters measured, and the changes noted, contribute to the effectiveness of phototherapy in the treatment of psoriasis remains uncertain.

Cowpox/catpox infection.

A 19-year-old veterinary nurse developed a cowpox/catpox virus (CPV) infection of her right third finger following a scratch from a tom cat suffering from pneumonia. The clinical course and investigation of the infection are described and the differential diagnosis discussed.

Immune responses of patients to orf virus infection.

Orf is a disease of sheep and goats which is caused by a parapox virus. It can be transmitted to humans, and is considered an occupational hazard by those handling sheep. In this paper we present the first report of both cell-mediated and humoral immune responses to naturally acquired orf virus infection in humans. Lymphoproliferative responses of peripheral blood mononuclear cells of patients to an orf virus antigen were vigorous soon after infection, but rapidly declined. Orf virus antibody levels, detected by ELISA, were shown to rise during infection. Western blot analysis confirmed this, and demonstrated that the antibody produced in response to the infection was directed against the 40-kDa viral surface tubule protein. Where direct comparisons were possible, the immune response of humans to orf virus infection was similar to that previously reported for sheep. Evidence was obtained suggesting that prior exposure to vaccinia virus (smallpox vaccination) provided no protection from subsequent orf virus infection. In addition, orf virus infection did not enhance immune responses to vaccinia virus antigens.

Primary nodular cutaneous amyloidosis--long-term follow-up and treatment.

A case of facial primary nodular cutaneous amyloidosis is reported. This illustrates: the striking appearance of this unusual condition; the investigations appropriate to establish the diagnosis and to exclude underlying systemic amyloidosis or a condition which might contribute to amyloidosis; and the difficulty of successful management. Initial investigation failed to reveal any evidence of systemic amyloidosis or an associated internal illness. Two amyloid nodules were excised, but 7 years later the patient developed further nodules on the adjacent facial skin and again sought dermatological advice. He was reinvestigated and again no underlying condition was found. A trial of cryotherapy was unsuccessful, but curettage and cautery produced a cosmetically acceptable result.

Sudden deepening of pigmentation during haemodialysis due to severe haemolysis.

A 37-year-old woman with chronic renal failure developed pain in the right flank during haemodialysis followed by rapid and dramatic deepening of pigmentation. Investigation indicated that the cause was severe haemolysis most probably due to mechanical damage to red blood cells passing through a stenosis in a dialysis blood line. Severe haemolysis should be suspected in subjects who suffer rapidly increasing pigmentation during dialysis. Such severe haemolysis should be recognized and treated rapidly since it may produce life-threatening systemic problems.

Similarities in intestinal humoral immunity in dermatitis herpetiformis without enteropathy and in coeliac disease.

Intestinal humoral immunity was examined in eight patients with dermatitis herpetiformis and normal jejunal histology (as determined by quantitative morphometry) on a gluten-containing diet. Jejunal aspirate was taken at the time of jejunal biopsy, and levels of total immunoglobulins (IgA, IgM, IgG) and specific antibody to gliadin and two other dietary proteins, betalactoglobulin and ovalbumin, were measured. The pattern of secretory immune responses in the dermatitis herpetiformis patients was similar to that in twenty-six patients with untreated coeliac disease--ie, higher than normal concentrations of IgA, IgM, and IgG and high levels of specific antibodies (IgA and IgM) to the three dietary proteins. Serum levels of IgA antigliadin were similar in the dermatitis herpetiformis and control (twenty-eight patients who underwent jejunal biopsy to exclude coeliac disease) groups, and serum levels of IgG antigliadin were intermediate between those of the control and coeliac disease groups. These findings suggest that investigation of gut humoral immunity may provide a diagnostic index of latent coeliac disease. The definition of coeliac disease as a permanent gluten-sensitive enteropathy may have to be revised if the proposed two-stage model is confirmed.