Pili bifurcati: occurring in association with the mosaic trisomy 8 syndrome.

The trisomy 8 mosaic syndrome may present in many different ways. We present a rare hair anomaly in a patient with this syndrome.

Adjuvant high-dose intravenous gammaglobulin in the treatment of pemphigus and bullous pemphigoid: experience in six patients.

At present, initial high-dose prednisone is the treatment of choice for patients with pemphigus and bullous pemphigoid. To reduce the risks associated with long-term corticosteroid treatment, other immunosuppressants are often given as steroid-sparing agents. Occasionally, the dose of steroids cannot be reduced. In this study, we report six patients with pemphigus vulgaris, pemphigus foliaceus and bullous pemphigoid, in whom the daily corticosteroid dose could only be tapered to acceptable, effective, maintenance levels following treatment with high-dose intravenous gammaglobulin.

Intermittent hair loss in a child with PIBI(D)S syndrome and trichothiodystrophy with defective DNA repair-xeroderma pigmentosum group D.

We describe a girl with photosensitivity (P), ichthyosis (I), brittle hair (B), impaired intelligence (I), possibly decreased fertility (D), and short stature (S). The clinical findings fit into the PIBI(D)S syndrome and trichothiodystrophy. A remarkable and probably unique observation for this disorder was the intermittent character of the scalp hair loss during infectious periods in this patient. Easy suntanning suggested photosensitivity and prompted DNA repair studies which demonstrated reduced UV-induced DNA repair synthesis. Subsequent studies have assigned this patient to xeroderma pigmentosum group D and suggested a specific deficiency of 6-4 photoproduct repair. An unaffected child was diagnosed in the next pregnancy of the mother.

Cutaneous manifestations and histologic findings in the hyperimmunoglobulinemia D syndrome. International Hyper IgD Study Group.

BACKGROUND AND DESIGN: The hyperimmunoglobulinemia D (hyper-IgD) syndrome is characterized by recurrent febrile attacks with abdominal distress, headache, and arthralgias. Physical examination reveals cervical lymphadenopathy in most cases and, sometimes, splenomegaly. Skin lesions have been observed in isolated cases during attacks. We summarize the features of skin lesions and the histopathologic findings in biopsy specimens in the hyper-IgD syndrome. RESULTS: A total of 44 patients with the hyper-IgD syndrome were studied. Thirty-five (79%) of them, 19 males and 16 females, had skin lesions during febrile attacks. Erythematous macules were the most common cutaneous manifestation (15 cases), followed by erythematous papules (12 cases); urticarial lesions (nine cases) and erythematous nodules (seven cases). Skin biopsy specimens of 10 patients with the hyper-IgD syndrome were available for review. The findings varied considerably. Most biopsy specimens showed mild features of vasculitis. Nonspecific findings were noted in five biopsy specimens; Sweet-like features in two, cellulitis-like findings in one, and deep vasculitis characteristics in one. CONCLUSIONS: Skin lesions are common in the hyper-IgD syndrome suggesting that they are a true manifestation of the disease.

Determination of the photoprotective efficacy of a topical sunscreen against UVB-induced DNA damage in human epidermis.

The ability of a chemical sunscreen with a sun protection factor of ten to protect human skin in situ against UVB-induced DNA damage (cyclobutyl thymine dimers) was evaluated. Biopsies were taken from the left buttock of ten human volunteers prior to UVB (280-315 nm) exposure. Subsequently, a sunscreen (n = 6) or vehicle (n = 4) was applied to a delineated area on the right buttock. After a period of 30 min, the entire buttock area was irradiated in a UVB cabin with one minimal erythema dose. Immediately after irradiation, biopsy specimens were obtained from the UVB-exposed sunscreen- or vehicle-treated right buttock and from the non-treated UVB-exposed left buttock. Dimers were assayed in skin sections by immunofluorescence microscopy with a monoclonal antibody against the cyclobutyl thymine dimer. The dimer-specific fluorescence from the epidermal cell nuclei, identified by counterstaining with propidium iodide, was quantified through computer-mediated image processing and analysis in skin sections of one sunscreen-treated and one vehicle-treated volunteer. After a single dose of UVB, significant dimer-specific nuclear fluorescence was observed and measured in the non-treated biopsy specimens. No nuclear fluorescence was observed and very little could be measured in the non-UVB-exposed skin and in the sunscreen-treated UVB-exposed skin respectively, indicating that the sunscreen offered good protection against the induction of cyclobutyl thymine dimers by UVB. This visual scoring is in general semiquantitative, but quantification through computer-mediated image processing was performed in one case for sunscreen-treated skin and in one case for vehicle-treated skin. Both assessments resulted in similar conclusions.(ABSTRACT TRUNCATED AT 250 WORDS)

Ultrastructural studies bearing on the mechanism of UVB-impaired induction of contact hypersensitivity to DNCB in man.

In both murine and human experimental systems, acute, low dose exposure of skin to ultraviolet B light (UVB) impairs the induction of allergic contact dermatitis (ACD) by haptens such as dinitrochlorobenzene (DNCB) in a significant proportion of individuals. By light microscopy, epidermal Langerhans cells (LC) have been reported to be depleted by UVB exposure as well as by epicutaneous hapten application, implying that LC may be the locus of action of the effects of both UVB and DNCB. However, light microscopy can not readily distinguish cell density changes secondary to LC necrosis from changes resulting from down-modulation of expression of LC surface molecules. Using a highly sensitive immunogold electron microscopic approach, we have evaluated the differential effects of UVB and/or DNCB on human epidermal LC. The results reveal that DNCB alone caused significant up-regulation of cell surface HLA class II expression on a very small number of LC, the major fraction of LC expressing normal levels of HLA class II. Furthermore, DNCB alone caused a modest reduction in the density of LC at the treated sites without evidence of cell necrosis. Treatment with UVB alone or UVB exposure followed by DNCB resulted in a reduction in the density of LC, with widespread evidence of LC necrosis. However, the few remaining intact LC were all intensely HLA class II-positive after UVB exposure followed by DNCB, whereas treatment with UVB alone did not result in changes in LC HLA class II expression. The findings that after DNCB painting only a small proportion of the LC were strongly HLA class II-positive, but after UVB exposure followed by DNCB all intact LC displayed significant up-regulation of cell surface HLA class II expression, imply that UVB exposure inhibits the migration of epidermal LC. This is consistent with the view that DNCB fails to induce ACD when hapten is painted on UVB-exposed skin because insufficient LC are available to initiate T cell activation in the draining lymph node.

Minimising the risks of PUVA treatment.

Psoralen photochemotherapy (PUVA) is a combination of orally administered psoralen and long wave ultraviolet-A radiation (UVA), and is one of the most effective forms of therapy for psoriasis. The unwanted effects of PUVA therapy can be divided into short and long term adverse effects. The short term adverse effects include erythema, pruritus, nausea and headache. While short term adverse effects are limited and reversible after discontinuation of treatment, potential long term adverse effects such as chronic actinic skin damage, dyskeratotic and precancerous skin conditions, nonmelanoma skin cancer, immunological alterations and cataract formation are of greater concern. Long term risks associated with PUVA therapy can be minimised by several measures. Careful patient selection is mandatory; for example, patients with chronic actinic damage and a history of skin cancer may bear a higher risk for the development of new cancers, and previous arsenic intake and ionising radiation also increase the risk of nonmelanoma skin cancers. Certain drug combinations make it possible to lower the UVA dose, which is important because of the dose-dependent increase in the incidence of squamous cell carcinomas in patients treated with PUVA. It has been demonstrated that 200 treatments or a total UVA dose of 1200 J/cm2 seems to be the threshold for development of nonmelanoma skin cancer. Shielding male genitalia during PUVA treatment is essential because of the increased risk of genital squamous cell carcinomas. Yearly dermatological examination to detect skin cancer at an early stage is highly advisable. Sunscreen use, protective clothing and avoidance of sun exposure reduce the uncontrolled dose of solar UV radiation. Other psoralens with a less carcinogenic potential can be used. UVA-opaque sunglasses during the entire period of increased photosensitivity after psoralen ingestion help avoid cataract formation. Assignment to PUVA ought to be based on the risk-benefit ratio for the individual patient and should be limited to those who can be monitored and controlled by informed, competent and conscientious physicians.

[Experience of sexuality in patients with psoriasis and constitutional eczema]. / Seksualiteitsbeleving bij patiënten met psoriasis en constitutioneel eczeem.

In order to determine the effect of chronic skin disorders on sexuality a cross-sectional study was carried out in the Dermatological Outpatient Clinic of Leiden University Hospital. Fifty-two patients with psoriasis and 25 patients with atopic dermatitis filled in a questionnaire which included items on sexual responsiveness and satisfaction. The response rate was 84%. One-third of the patients, especially those with psoriasis, had problems with dating and starting sexual relationships, and were embarrassed in these relationships. The sexual responsiveness of both male and female patients was below that in the normal population. Women appeared to have more problems in this area then men. Their sexual satisfaction was lower than in the average Dutch population, whereas in men this trend was found to be reversed. Sexual responsiveness did not correlate with the extent of the skin disease or location around genital areas, but was associated with self-esteem and the number of emotional complaints. In the treatment of patients with chronic skin disorders attention should be paid to sexual problems that may arise. Groups that are especially affected are females and young psoriatics who have their first sexual relationship.

Presence and interpretation of vascular immune deposits in human skin: the value of direct immunofluorescence.

Direct immunofluorescence investigation of the skin is an easy and valuable technique to establish the diagnosis immune complex vasculitis. Vascular immune deposits can be found in 60-80% of all cases. Absence of vascular immune deposits, however, does not exclude vasculitis per se, since the dynamics of the vasculitic process limit their presence in time. Knowledge of these dynamics is indispensable for both the clinician and the interpreter. Several practical options are discussed that may increase sensitivity. The specificity of vascular immune deposits has become a complex matter. Different immunoglobulin classes have different specificity, indicating that specificity also depends on the relative incidence of individual immunoglobulin classes. Some of these relative incidences seem to have changed over the years. Furthermore, several non-vasculitic diseases and conditions have now been described, that may show fluorescent pictures similar to vasculitis and thus decrease specificity.

Decreased expression of decay-accelerating factor on endothelial cells of immune complex-mediated vasculitic skin lesions.

Endothelial cells may be damaged directly by the membrane attack complex of complement in immune complex vasculitis of the skin. However, for endothelial cell membrane injury to occur, normal regulatory mechanisms must fail. One of the main complement regulatory proteins of endothelial cells is decay-accelerating factor, a surface protein which interferes with either the classical or alternative pathway C3 and C5 convertases. We have investigated the expression of decay-accelerating factor in 4 patients with histologically proven cutaneous immune complex vasculitis, using an immuno-electronmicroscopic technique. We demonstrated that endothelial cells of upper dermal vessels in vasculitic lesions were almost completely devoid of decay-accelerating factor. By contrast, the expression of this protein on endothelial cells in uninvolved skin of the patients was the same as in skin of healthy volunteers. As yet, the mechanism responsible for depletion of decay-accelerating factor is not clear. Absence of decay-accelerating factor may follow enzymatic release from the phosphatidylinositol anchor, proteolytic stripping from the cell membrane or a down-regulation of decay-accelerating factor synthesis. Regardless of mechanism, endothelial cell injury or death could serve a phlogistic function to facilitate complement-mediated destruction of endothelial cells for removal and repair.

A case of seminal fluid allergy successfully treated with immunotherapy in a one-day rush procedure.

A 28-year-old woman was treated for seminal fluid allergy with immunotherapy using a one-day 'rush' procedure. Apart from minor anaphylactic symptoms, no serious side effects were noted during or after hyposensitization or boostering. Five weeks after the start of the hyposensitization, she was free of symptoms after unprotected coitus.

IgD immune complex vasculitis in a patient with hyperimmunoglobulinemia D and periodic fever.

We describe a 27-year-old Dutch woman with the hyperimmunoglobulinemia D and periodic fever syndrome. During febrile attacks she occasionally presented with skin lesions on the distal parts of her upper and lower extremities, with the histologic picture of a leukocytoclastic vasculitis. Clear perivascular deposits of IgD and C3 were presented in early lesional skin on immunofluorescence investigation. Circulating IgD immune complexes were demonstrated on several occasions, both during and in between clinical attacks. These findings are consistent with an IgD immune complex-mediated pathogenesis for the skin lesions. In 10 patients with other forms of immune complex vasculitis of the skin, minimal perivascular deposits of IgD were found in four cases. In these cases, however, IgD was never found as the solitary immunoglobulin class.

Cutaneous immunofluorescence in ankylosing spondylitis. Absence of correlation with disease activity.

Biopsy specimens of normal skin from 43 patients with ankylosing spondylitis (AS) were studied for immunoglobulin and complement deposition by immunofluorescence and for histological abnormalities by light microscopy. The results were compared with those of 17 healthy subjects. Perivascular deposits of IgA, IgG, IgM and C3 were found in 26, 47, 56 and 33%, respectively, of the patients with AS. Skin deposits of IgA, IgG and C3 occurred significantly more frequently in patients with AS compared to healthy subjects. Perivascular mononuclear cell infiltration was found in only 8 (19%) of the patients with AS. The results of both immunofluorescence and histologic studies did not correlate with disease duration, disease activity, extraarticular features or the presence of circulating immune complexes. Our findings suggest a role of humoral immunopathological mechanisms in AS but also show that cutaneous immunofluorescence cannot serve as a marker of disease activity.

Complement-mediated endothelial cell damage in immune complex vasculitis of the skin: ultrastructural localization of the membrane attack complex.

Activation of the complement system is an important element in our concept of the pathomechanism of immune complex (IC) vasculitis. Both deposition of IC and attraction of polymorphonuclear leukocytes (PMN) are effected by products of complement activation. Actual tissue damage, however, is believed to be caused by PMN penetrating the vessel wall. Our former finding that deposits of membrane attack complex of complement (MAC) are found predominantly in skin lesions of patients with IC vasculitis and not in perilesional skin, has raised the question whether the complement system itself (by way of the MAC) contributes to tissue damage. Our present study shows the ultrastructural localization of MAC in lesional and clinically uninvolved skin in two patients with a cutaneous IC vasculitis. Lesional skin deposits of MAC were found on endothelial cells (EC) of upper dermal vessels and on infiltrating PMN. Uninvolved skin deposits of MAC were found on some EC, but clearly to a lesser extent than on EC of the lesional skin. In the skin of two healthy controls MAC was only found sporadically on EC. Deposits of MAC on EC in the lesional skin were often associated with a typical form of local cell swelling. This local form of endothelial cell swelling was incidentally seen in vessels of clinically uninvolved skin, but not in the skin of the two controls. The association of the endothelial cell swelling with deposits of MAC suggests that the complement system can have a direct damaging effect on EC in IC vasculitis by the assembly of MAC on the endothelial cell membrane.