Pronounced and early acne in Apert's syndrome: a case successfully treated with oral isotretinoin

An unusual case of widespread acne unresponsive to treatment with early onset in a child with Apert's syndrome is presented. The patient eventually responded to oral isotretinoin therapy. The morphological profile of the sebaceous glands and the expression of proliferative markers and androgen receptors were evaluated in seboblasts and sebocytes using morphological, ultrastructural and immunohistochemical techniques. There were no significant differences in staining for proliferative markers and nuclear expression of androgen receptors in the glands from the patient and four healthy controls. Our results support the view that acne in Apert's syndrome is not sustained by abnormalities of the sebaceous glands demonstrable with conventional morphological techniques, and that it does not depend on an increased expression of androgen receptors.     

Klinefelter‐Syndrom mit Mischkollagenose (Sharp‐Syndrom) und postthrombotischem Syndrom bei Thrombophilie

A 43‐year‐old male with eunuchoid body proportions and a history of deep venous thromboses in the right leg presented with recurrent ulcers in the right perimalleolar region for 6 years. Karyotyping revealed a 47 XXY Klinefelter's syndrome, while serologic testing showed protein S deficiency, hyperhomocysteinemia and positive lupus anticoagulant. He also had mixed connective tissue disease (Sharp's syndrome) with acrosclerosis, proximal finger edema, Raynaud's phenomenon, and high titers of ANA and U1‐RNP‐antibodies, as well as osteoporosis. There is evidence that patients with Klinefelter's syndrome are prone to develop connective tissue diseases and thrombophilia as a result of low androgen levels. Substitution of testosterone in Klinefelter's syndrome can have a favorable therapeutic effect on the associated connective tissue disease, thrombophilia and osteoporosis.     

Serum β2 microglobulin in recurrent aphthous stomatitis and Behçet's syndrome

β₂Microglobulin (β₂m), a constituent of cell surface histocompatibility antigens, was measured in scrum from twenty-eight patients with recurrent aphthous stomatitis, twenty-four patients with Behçet's syndrome and twenty-eight matched controls. Serum β₂m concentrations were significantly greater in recurrent aphthous stomatitis and in Behçet's syndrome than controls, but failed to differentiate the two diseases.     

Immunohistochemical evaluation of androgen receptors in genital and extragenital lichen sclerosus: evidence for loss of androgen receptors in lesional epidermis.

BACKGROUND: Reduction of lichen sclerosus has been seen with topical testosterone, and spontaneous resolution has been attributed to increasing androgen levels. OBJECTIVE: Our purpose was to investigate the role of androgens in lichen sclerosus by studying lesional skin and site-specific normal skin for the presence of androgen receptors. METHODS: Immunoperoxidase staining for androgen receptors was performed on lesional tissue from 31 patients and microscopically compared with site-specific normal skin. RESULTS: Androgen receptors were present in normal genital and extragenital skin. Lesional genital and extragenital areas showed decreased staining compared with site-specific controls. Finally staining was decreased in histologically well-developed lesions compared with early lesions. CONCLUSION: This study provides evidence for the loss of androgen receptors with disease progression in both genital and extragenital skin affected by lichen sclerosus. These findings support a hormonal pathogenesis of lichen sclerosus and may be significant in the treatment of the disease.     

Hormonal interaction of androgen and estrogen receptors in normal skin and in acne

Hormone metabolism in skin affected with acne has been investigated by determination of androgen and estrogen receptors with the help of saturation analysis. The results have been compared with data of an age-corresponding control group. The investigation has been performed on 55 male and 11 female volunteers with acne in their lesions as well as unaffected areas. Androgen and estrogen serum levels have been determined as additional endocrine parameters. Testosterone serum levels were slightly elevated in about 11 percent of the male patients, while the percentage for the female patients might be higher as far as can be judged on account of small number of patients. The lack of correlation between estrogen/androgen receptors and their corresponding serum levels leads to the conclusion that the hormone metabolism is situated in the periphery, being independent of the central endocrine regulation. Similar findings for distribution and receptor levels in both healthy and involved skin of acne patients revealed a significant discrepancy in comparison to corresponding evaluations found in healthy patients. There results point out to an elevated dependency on hormonal influences of the entire integument of acne patients. Estrogen receptors could be found in both acne patients and controls.     

Increased anti–Epstein—Barr virus antibodies in epidermotropic cutaneous T–cell lymphoma: a study of 64 patients

Epstein—Barr virus (EBV) is often associated with non–Hodgkin's T–cell lymphomas and has recently been found in the lesions of mycosis fungoides and Sézary syndrome. We sought to determine whether the anti–EBV antibody profile was disturbed in mycosis fungoides and Sézary syndrome and whether there are particular profiles characteristic of disease stage. Anti–EBV antibodies (anti–VCA,–EA and –EBNA) were studied in the sera of 64 patients. An immunoenzymatic technique was used, and the results were compared with the same number of age– and sex–matched healthy controls. Patients with mycosis fungoides and Sézary syndrome developed higher anti–VCA antibody titres (median 1200) than controls (median 320). Thirty–seven patients had anti–VCA ≥ 1200 vs. 19 controls (P<0.01). These elevated anti–VCA antibody titres were associated with positive EA in 19 patients versus three controls. No differences were found between the illness stages. Anti–EBV antibodies were most often found in mycosis fungoides and Sézary syndrome when the serological profile was similar to that of cellular immune deficiencies and EBV–related non–Hodgkin's lymphoma. EBV could be involved, either directly on lymphocytes or, more likely, indirectly by chronic antigenic stimulation.     

The significance of immunohistochemistry in the skin pathergy reaction of patients with Behçet''s syndrome

Background Behçet's syndrome is a chronic systemic immuno‐inflammatory disorder affecting multiple organs with generalized vasculitis of arteries and veins. Although the aetiology is still unknown, endothelial dysfunction is one of the most prominent features in Behçet's syndrome. The skin pathergy reaction (SPR) is a non‐specific hyperreactive lesion formation that is one of the major features and diagnostic criteria of the disease. It develops after 24–48 h at the site of the needle‐prick, especially in the exacerbation period, and it is very similar to the erythematous papules or pustules that appear spontaneously in patients with Behçet's syndrome. Therefore, an investigation into the formation of the SPR lesion may contribute to the pathophysiology of skin lesions of this unique disorder. Objective To evaluate the immunological features of SPR formation by assessing the immunohistochemical staining of cell adhesion molecules and endothelial growth factor markers such as E‐selectin, P‐selectin and endoglin (CD 105). Methods Patients with Behçet's syndrome showing positive (n = 15) or negative (n = 10) SPR and 15 age‐ and sex‐matched hospital‐based healthy control subjects from a similar ethnic background were included in this study. Patients were divided into active and inactive stage by clinical findings and acute‐phase reactant parameters including erythrocyte sedimentation rate (ESR) and neutrophil count. Punch biopsy specimens were obtained both from the lesion site on the forearms at 48 h and from normal skin approximately 5 cm adjacent to the SPR site. A biopsy was also obtained from the test application site in Behçet's syndrome patients with negative SPR and healthy volunteers. Biopsy specimens were then evaluated by immunohistochemical staining. Results Immunohistochemical examination demonstrated a mixed inflammatory cell infiltrate around the vessels and skin appendages that extended somewhat into the deep dermis. A positive segmental staining of E‐selectin and P‐selectin was noted in the endothelial cells of biopsies obtained from the patients with positive SPR. A positive segmental staining of CD 105 in the endothelial cells was also observed in the same group of patients. However, the immunostaining of the same markers was found to be negative in the biopsies obtained from normal skin of SPR‐positive patients, SPR‐negative patients and healthy control subjects. Both acute‐phase reactant levels were significantly higher in the active stage than in inactive patients or healthy controls. Conclusion Interaction of cellular adhesion molecules together with endothelial proliferation may play an important role in the formation of SPR lesions in patients with Behçet's syndrome. The involvement of the vascular endothelium in a large number of diseases including Behçet's syndrome supports the importance of vascular‐specific adhesion molecules for their aetiopathogenesis.     

Androgen Status in Adolescent Women with Acne Vulgaris

Androgens are essential for the development of acne. The object of this study was to elucidate the androgen status of women with adolescent (Tanner's stage IV–V) acne alone and compare them to age-matched normal controls. We measured serum levels of total testosterone (T), free testosterone (FT), dihydrotestosterone (DHT), and dehydroepiandrosterone sulfate (DHEA-S) in 15 women with adolescent acne and 13 age-matched healthy controls. No significant differences were found between the mean levels of T, FT or DHT levels in patients and controls. However, the mean levels of DHEA-S in the patient population (1886 ± 829 ng/ml) were significantly (p<0.05) higher than normal controls (1287 ± 620 ng/ml). There was also no correlation between androgen levels and acne severity. Thus it is unlikely that serum androgens play a principal role in women with adolescent acne.     

Acute febrile neutrophilic dermatosis (Sweet''s syndrome) and adenocarcinoma of the rectum

Sweet's syndrome is a distinctive dermatosis that usually occurs as an idiopathic disorder. About 10% of cases have occurred in patients with myeloproliferative disease. Seven cases have been described with Sweet's syndrome in conjunction with a solid malignancy. We report a patient with Sweet's syndrome in association with an adenocarcinoma of the rectum. We believe that this syndrome may reflect a clinical manifestation of underlying myeloproliferative or solid malignancy. Sweet's syndrome is a characteristic dermatosis of acute onset, consisting of pseudovesicular, tender nodules and plaques, fever, arthritis and a neutrophilic leukocytosis. The associaton of Sweet's syndrome with myeloproliferative diseases has been reported several times. Acute myeloid leukaemia may occur in up to 10% of patients with Sweet's syndrome.^1,2 Reports of associations of the syndrome with non-myeloproliferative malignancies are uncommon. We report herein a patient with Sweet's syndrome and an adenocarcinoma of the rectum.     

Leg ulcers in Klinefelter's syndrome – further evidence for an involvement of plasminogen activator inhibitor-1

An abnormality in platelet aggregability or fibrinolysis, namely elevated activity of plasminogen activator inhibitor-1 (PAI-1), has been recently documented in patients suffering from Klinefelter's syndrome associated with leg ulceration without underlying venous insufficiency. To determine whether increased PAI-1 activity is a general feature of Klinefelter's syndrome, or more specifically associated with leg ulceration, we investigated PAI-1 influencing parameters and PAI-1 activity in two groups of patients: (i) Klinefelter patients suffering from leg ulceration (n=7); and (ii) Klinefelter patients without leg ulceration (n=6). On analysing PAI-1 influencing parameters such as age, body mass index, triglycerides, C-reactive protein, testosterone, smoking behaviour, the presence of diabetes mellitus, and artierial hypertension, respectively, we found no statistically significant differences between the two groups. However, PAI-1 activity in group 1 was highly significantly elevated compared with that in group two patients (P<0.005). We conclude that (i) PAI-1 activity is not elevated in Klinefelter's syndrome in general; (ii) elevation of PAI-1 activity in patients suffering from Klinefelter's syndrome does not appear to be secondary to PAI-1 influencing parameters; and (iii) elevation of PAI-1 activity may play a crucial role in the pathogenesis of leg ulceration in Klinefelter's syndrome. Therefore, a therapy for leg ulceration in Klinefelter's syndrome that aims to return the elevated PAI-1 activity to normal should be explored.     

HORMONAL STATUS IN POSTMENOPAUSAL ANDROGENETIC ALOPECIA

The development of androgenetic alopecia is thought to be caused by increased androgen action on hair follicles with menopause. Testosterone, estradiol and sex hormone binding globulin (SHBG) serum levels were determined in ten postmenopausal women with androgenetic alopecia and in ten sex and age matched healthy controls. No statistically significant differences were found in the hormone levels between the patients and the controls. These findings suggest that a genetically determined functional alteration of androgen receptors and/or a metabolic disturbance may exist in the hair follicle keratinocytes in androgenetic alopecia.     

The spectrum of psoriasis in an Irish HIV population

Object Report of the pattern of psoriasis and response to therapy in psoriatic patients infected with HIV-1. Setting Department of Dermatology, St. James's Hospital, Dublin Subjects Seven HIV-positive patients with psoriasis: six seen as part of a prospective dermatological assessment of all HIV-positive patients; one separately referred Observations Three patients had psoriasis vulgaris which was limited and responsive to conventional therapy; one also had flexural psoriasis which proved difficult to control. Four patients had features of keratodermia blennorrhagicum; their skin disease was severe and warranted systemic treatment in three cases, without adverse affects. However, only one patient fulfilled the complete criteria for Reiter's syndrome. As six of the seven cases occurred in a prospective age- and sex-matched controlled study of skin disease in 92 HIV-1-infected patients in which only two controls had psoriasis, it would suggest that there may be an increased prevalence of psoriasis in the HIV-1 population.     

The premature ageing syndromes

Eight patients are reported who all have one feature in common, the appearance of premature ageing. Six of these could be accurately classified into previously described syndromes, but the other two may represent a new syndrome which we have called metageria. Clinical and other features of these two individuals are compared with three patients with acrogeria (Gottron's syndrome), one with pangeria (Werner's syndrome), one with progeria (Hutchinson-Gilford syndrome) and one with a total lipodystrophy (Lawrence's syndrome).     

Clinical and immunological effects of adsorptive myeloid lineage leukocyte apheresis in patients with immune disorders

Adsorptive granulocyte and monocyte apheresis (GMA) with the Adacolumn^® is an extracorporeal treatment, which uses cellulose acetate (CA) beads as adsorptive leukocytapheresis carriers designed to remove elevated and potentially activated myeloid lineage leukocytes. Reports on the clinical efficacy of GMA in patients with skin lesions have appeared in the published work. Dermatological diseases, which are known to respond to GMA, include pyoderma gangrenosum, skin lesions of Behçet's disease, rheumatoid arthritis, pustular psoriasis, psoriatic arthritis, adult‐onset Still's disease, Sweet's syndrome, cutaneous allergic vasculitis and systemic lupus erythematosus rashes. In association with clinical studies, efforts to understand the mechanisms of GMA have made significant progress. GMA selectively depletes elevated myeloid lineage leukocytes through binding between blood immunoglobulin G or complement iC3b, which form on the surface of CA beads and the Fcγ receptors or complement receptors expressed on the myeloid lineage cells. However, GMA has immunomodulatory effects including down‐modulation of inflammatory cytokine profile, changes in leukocyte surface receptors and induction of regulatory T cells. These actions render GMA a unique non‐pharmacological treatment option for patients with chronic dermatoid conditions, which are difficult to treat with pharmacological preparations.     

ACUTE FEBRILE NEUTROPHILIC DERMATOSIS (SWEET'S SYNDROME)

Background. Sweet's syndrome is well recognized and not infrequently diagnosed in Spain; however, the range of clinical and pathologic expression may not have been fully realized. Methods. We reviewed 30 consecutive Spanish cases of Sweet's syndrome diagnosed in our department from 1979 to 1990, with special attention to clinical and histopathologic findings. Results. Distinctive clinical features in our series included oral mucosa lesions in four patients (13%), development of pathergy phenomenon in one case, concurrent nodular lesions resembling erythema nodosum on the limbs in nine cases (30%), and lung involvement in two patients. Infectious disease and drug treatment were recorded as possible triggering factors of Sweet's syndrome in eight and seven patients respectively. Associated underlying systemic disorders were present in 15 (50%) of our patients. The most frequent associations were hematologic neoplasia in four patients, solid neoplasia in two, and chronic idiopathic inflammatory bowel disease in three patients. Dressler's syndrome and sicca syndrome were found in one patient each. Histopathologic studies of skin biopsy specimens obtained at presentation disclosed typical features of Sweet's syndrome in all cases. Epidermal involvement, with variable degrees of spongiosis, exocytosis of polymorphonuclear leukocytes and keratinocyte necrosis, was a prominent feature in 83% of biopsy specimens. Conclusions. Further characterization of the clinicopathologic spectrum of Sweet's syndrome is necessary as the recognition of the full spectrum of this syndrome will improve our diagnostic abilities and provide a solid clinical basis for prospective studies that allow dissection of the intricate pathomechanisms involved in this fascinating disorder.     

Sweet's syndrome and malignancy in the U.K.

Acute febrile neutrophilic dermatosis (Sweet's syndrome) is reported to be a marker for underlying malignancy. Much of the evidence for this is based on case reports, small series of cases and reviews of the literature. In order to clarify the association with malignancy and determine the common clinical features of Sweet's syndrome, we reviewed the case notes of patients presenting to six dermatology units in the U.K. Eighty-seven cases of histologically proven Sweet's syndrome were reviewed. Fourteen patients (16%) developed associated malignancy, predominantly haematological, two patients (2%) had a history of previous malignancy and four patients (5%) had premalignant conditions (monoclonal gammopathy, two: myelodysplasia, two). Malignancy developed up to a year after presentation with Sweet's syndrome. Patients with associated malignancy were more likely to be anaemic (P<0·01) at presentation, had a lower mean platelet count (207 × 10⁹/L vs. 332 × 10⁹/L: P<0·003) and were, on average, older (59 years vs. 49 years: P = 0·002). Contrary to previous reports, a greater percentage of females developed malignancy than males.     

Haber's Syndrome

Haber's syndrome is a rare genodermatosis characterised by an early onset rosacea-like eruption associated with multiple truncal keratoric lesions. The present study reports the clinical presentation, histology and response to therapy of two cases of Haber's syndrome. The cases presented with the typical features of Haber's syndrome. Case 1 also had diffuse palmoplantar keratoderma and prominent nail cuticles, and case 2 had diffuse palmar keratoderma. These features have not been previously reported in Haber's syndrome. In the present study Haber's syndrome is reviewed, and its relationship to Dowling-Degos disease and acropigmentation of Kitamura are discussed.     

The Coexistence of Psoriasis Vulgaris,Sjögren's Syndrome,and Hashimoto's Thyroiditis

A 52-year-old woman presented with psoriasis vulgaris, Sjögren's syndrome, and Hashimoto's thyroiditis with a 5-year history. She had a number of immunological abnormalities and typical psoriatic plaques over her entire body. The relationship between psoriasis, Sjögren's syndrome, and Hashimoto's thyroiditis is discussed from the viewpoint of immunology, and similar cases in the literature are reviewed. This is the first report of a coexistence of psoriasis vulgaris, Sjögren's syndrome, and Hashimoto's thyroiditis.     

Diffuse lentiginosis in a patient with Werner's syndrome—a possible association with incomplete leopard syndrome

A classical case of Werner's syndrome is described. In addition to the numerous skin changes that are typically associated with Werner's syndrome, our patients also displayed diffuse lentiginosis, and several of the clinical features of leopard syndrome. Histopathological and ultrastructural findings from a hyperpigmented maculae displayed the typical features of a simple lentigo. A striking feature was the presence of melanosomes in Langerhans cells as has been reported in the leopard syndrome. A possible generalized mesodermal defect has been suggested in Werner's syndrome, while the basic defect in the leopard syndrome is thought to be of neuroectodermal origin with pleiotropic changes in the organs derived from the mesoderm. Our patient, with incomplete leopard syndrome and typical Werner's syndrome, may be an example of an association of genetic defects affecting both tissues of neuroectodermal and mesodermal origin.     

Content of 5-alpha-reductase (type 1 and type 2) mRNA in dermal papillae from the lower abdominal region in women with hirsutism

BACKGROUND: Androgens influence the growth of terminal hair. The dermal papilla contains androgen receptors and the enzymes 5-alpha-reductase types 1 and 2. Both of these enzymes convert testosterone to the more active androgen, 5-alpha-dihydrotestosterone. The male distribution pattern of terminal hair in females is termed hirsutism. It is most common among women with hyperandrogenism; however, it may also affect patients with normal androgen levels (idiopathic hirsutism). OBJECTIVES: The aim of this study was to assess the expression of 5-alpha-reductase types 1 and 2 mRNA in dermal papillae from the lower abdominal skin in women with hirsutism. METHODS: The study included 42 subjects, 24 with a diagnosis of polycystic ovary syndrome (PCOS) and 18 with idiopathic hirsutism (IH). In all patients, free serum testosterone was measured. RESULTS: The mean +/- SD concentration of free serum testosterone was 7.2 +/-5.3 pmol/L in the total group of patients, 10.8 +/- 4.0 pmol/L in patients with PCOS, and 2.5 +/- 1.7 pmol/L in patients with IH. Quantitative analysis was then performed for the mRNA of 5-alpha-reductase types 1 and 2, both of which were found within the dermal papillae from the lower abdominal skin region. The number of mRNA copies/microg of total RNA for 5-alpha-reductase type 1 was statistically significantly higher than that for type 2 in both groups of examined patients. We also demonstrated a positive correlation between the number of mRNA copies/microg of total RNA for 5-alpha-reductase types 1 and 2 and the concentration of free serum testosterone in women with PCOS and IH. Considering all patients together, we found a positive correlation between the number of mRNA copies/microg of total RNA for 5-alpha-reductase type 2 and the concentration of free serum testosterone. There was also a tendency towards a positive correlation between the number of mRNA copies/microg of total RNA for 5-alpha-reductase type 1 and the concentration of free serum testosterone. CONCLUSION: The results of our study suggest that testosterone increases expression of 5-alpha-reductase types 1 and 2 in dermal papillae from the lower abdominal region in patients with hirsutism.