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Background: Chronic hand eczema (CHE) is a highly prevalent, heterogeneous, skin disease that encompasses different aetiological and clinical subtypes. Severe CHE without atopic dermatitis has been associated with systemic inflammation; yet it remains unknown if specific CHE subtypes leave distinct, systemic, molecular signatures., Objectives: To characterize the inflammatory plasma signature of different aetiological and clinical CHE subtypes., Methods: We assessed expression levels of 266 inflammatory and cardiovascular disease risk plasma proteins as well as filaggrin gene mutation status in 51 well-characterized CHE patients without concomitant atopic dermatitis and 40 healthy controls. Plasma protein expression was compared between aetiological and clinical CHE subgroups and controls both overall and according to clinical CHE severity. Correlation analyses for biomarkers, clinical and self-reported variables were performed., Results: Very severe, chronic allergic contact dermatitis (ACD) on the hands was associated with a mixed Type 1/Type 2 systemic immune activation as compared with controls. Circulating levels of Type 1/Type 2 inflammatory biomarkers correlated positively with clinical disease severity among CHE patients with ACD. No biomarkers were found, that could discriminate between aetiological subtypes, for example, between ACD and irritant contact dermatitis. Hyperkeratotic CHE showed a distinct, non-atopic dermatitis-like, systemic footprint with upregulation of markers associated with Type 1 inflammation and tumour necrosis factor alpha, but not Type 2 inflammation. Increased levels of CCL19 and CXCL9/10 could discriminate hyperkeratotic CHE from both vesicular and chronic fissured CHE, whereas no difference was found between the latter two subtypes., Conclusion: Profiling of systemic biomarkers showed potential for identifying certain CHE subtypes. Peripheral blood levels of inflammatory biomarkers were associated and correlated with the clinical disease severity of chronic ACD on the hands, underlining that this is a systemic disease. We question whether hyperkeratotic CHE should be classified as eczema., (© 2023 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Background: Identification of myositis-specific autoantibodies (MSAs) for dermatomyositis (DM) could allow the characterization of an antibody-associated clinical phenotype., Objective: We sought to define the clinical phenotype of DM and the risk of cancer, interstitial lung disease (ILD) and calcinosis based on MSA., Methods: A 3.5-year multicentre prospective study of adult DM patients was conducted to determine the clinical phenotype associated with MSAs and the presence of cancer, ILD and calcinosis., Results: MSAs were detected in 47.1% of 117 included patients. Patients with antimelanoma differentiation-associated protein-5 antibodies (13.7%) had significantly more palmar violaceous macules/papules [odds ratio (OR) 9.9], mechanic's hands (OR 8), cutaneous necrosis (OR 3.2), articular involvement (OR 15.2) and a higher risk of ILD (OR 25.3). Patients with antitranscriptional intermediary factor-1 antibodies (11.1%), antinuclear matrix protein-2 antibodies (6.8%) and antiaminoacyl-transfer RNA synthetase (5.1%) had, respectively, significantly more poikiloderma (OR 5.9), calcinosis (OR 9.8) and articular involvement (OR 15.2). Cutaneous necrosis was the only clinical manifestation significantly associated with cancer (OR 3.1)., Conclusion: Recognition of the adult DM phenotype associated with MSAs would allow more accurate appraisal of the risk of cancer, ILD and calcinosis., (© 2017 European Academy of Dermatology and Venereology.)

Background: Recent studies have found that alitretinoin can induce clinically significant responses in subjects with severe chronic hand eczema (CHE) unresponsive to topical corticosteroids., Aims: To assess the pharmacokinetics (PK), efficacy and safety of alitretinoin 10 or 30 mg once daily., Methods: This was a randomized, double-blind study, which enrolled 32 subjects aged 18-75 years with CHE unresponsive to potent topical corticosteroids. Subjects received alitretinoin 10 mg (n = 16) or 30 mg (n = 16) once daily for 12 or 24 weeks. Standard PK variables [area under the curve (AUC) of plasma concentration vs. time, maximum plasma concentration (C(max)), time to maximum plasma concentration (t(max)), elimination half-life (t(1/2)), total systemic clearance (CL/F) and volume of distribution (Vd/F)] were determined for alitretinoin and metabolites. Efficacy was assessed using the Physician's Global Assessment (PGA) scale., Results: Chronic administration of alitretinoin for up to 24 weeks did not result in accumulation or time-dependent changes in the disposition of alitretinoin. Exposure was found to be proportional to dose. Systemic exposure (AUC) to alitretinoin was proportional to dose for 10 and 30 mg alitretinoin; 62.8% of subjects achieved clear/almost clear hands in the 30 mg group and 12.5% in the 10 mg group. Alitretinoin was well tolerated., Conclusions: Chronic administration of alitretinoin for 12-24 weeks did not lead to accumulation or time-dependent changes in drug exposure. Alitretinoin was effective and well tolerated in the treatment of subjects with moderate or severe CHE unresponsive to potent topical corticosteroids., (© 2011 The Author(s). Clinical and Experimental Dermatology © 2011 British Association of Dermatologists.)

Background: Necrolytic acral erythema (NAE) is a distinct skin entity and is strongly associated with chronic hepatitis C virus (HCV) infection. It is distinguished by its acral location, typical clinical and histopathologic features, and positive serum antibodies against HCV. Most cases have been treated with variable success using oral zinc, amino acids, and interferon with or without ribavirin therapy., Methods: We report two patients with the clinical and histopathologic features of NAE; however, both tested seronegative for HCV. Both patients were treated with oral zinc acetate with good response, with one showing a partial relapse after stopping oral zinc. The clinical features, histopathologic findings, association of HCV, and treatment of NAE in different case reports were reviewed., Conclusion: NAE has a strong association with HCV, particularly in prevalent countries such as Egypt. Nevertheless, it may occur independently without HCV association, and oral zinc may prove to be a less toxic therapeutic option for such cases.

Objective: Epidemiological studies have convincingly demonstrated a positive association between LDL-cholesterol (LDL-C) and coronary artery disease but, in the case of HDL-C, there is an inverse association. Administration of high doses of the antifungal agent ketoconazole (800 mg/d) reduces serum concentrations of total cholesterol and LDL-C and there is a tendency for an increase in HDL-C. Our goal was to examine whether high-dose itraconazole raises HDL-C in subjects with normal levels of cholesterol., Patients and Methods: 8 male patients with onychomycosis received 2 one-week cycles of treatment with itraconazole at a dose of 400 mg once daily in an open, prospective exploratory trial. Serum levels of itraconazole and its active metabolite hydroxyitraconazole were determined using high-performance liquid chromatography at the end of each treatment cycle. Fasting levels of serum lipoproteins and triglycerides were measured twice using routine enzymatic assays at the beginning and end of each cycle. The effects of itraconazole and hydroxyitraconazole on HDL-C metabolism were assessed in vitro using a human Caco-2 cell line and analyzing apoA-I levels with an enzyme-linked immunosorbent assay., Results: During itraconazole treatment total cholesterol and LDL-C decreased on average by 12% (p < 0.001) and 17% (p < 0.001), respectively, whereas HDL-C increased by 21% (p < 0.001). The ratio LDL: HDL-C, an index of atherogenic risk, decreased by 30% (p < 0.001). Incubation of Caco-2 cells in the presence of itraconazole and hydroxyitraconazole for 3 hours resulted in a significant increase in apoA-I concentration in the medium (913 and 412%, respectively) compared with control., Conclusion: In addition to its inhibitory effect on cholesterol synthesis, high-dose itraconazole (400 mg/d) causes a significant decrease in serum LDL-C and, in contrast to ketoconazole, a significant increase in HDL-C. In vitro studies with Caco-2 cells indicate that the latter observation might be caused by an increase in apoA-I levels.

In the period 1994-2002, we saw 71 patients with sclerotic skin changes; 66 were diagnosed with systemic sclerosis (SSc) while five (7%) were diagnosed with pseudoscleroderma associated with various malignancies. The mean duration of disease in these five patients was significantly shorter than that of patients with SSc. The incidence of positive antinuclear antibodies, Raynaud's phenomenon or oesophageal involvement in patients with pseudoscleroderma was significantly lower than that in patients with SSc. The distributions of skin sclerosis varied in each case. Serum basic fibroblast growth factor (bFGF) levels in the five patients with pseudoscleroderma were very elevated compared with levels in controls. Elevated expression of bFGF was detected on fibroblasts of affected skin and in one lung-cancer tissue sample obtained by excision.

The present work was undertaken to study in hairdressers exposed to several irritants and allergens (prevalently hair-dyeing) and affected by hand contact dermatitis the possible correlation between exposure and direct-oxidative DNA damage, production of tumour necrosis factor alpha (TNFalpha) and allergic inflammatory disease. We evaluated in 19 hairdressers with hand contact dermatitis, 14 allergic contact dermatitis (ACD) and 5 irritant contact dermatitis (ICD) and in a selected control group TNFalpha serum levels by ELISA and direct-oxidative DNA damage by Fpg (formamido-pyrimidine-glycosylase)-modified Comet test on blood. Hairdressers were divided on the basis of number of hair-dyeing carried out weekly into 2 groups: low-exposure (<60 hair-dyeing/week) and high-exposure hairdressers (>or=60 hair-dyeing/week) that reflect also the exposure to other allergens and irritants and 2 different tasks (hairdressers and apprentice hairdressers, respectively). Serum levels of TNFalpha in hairdressers with ACD were significantly higher than controls with a correlation to exposure level. Significant DNA damage in ICD hairdressers with higher exposure as compared to controls was found. These findings suggest that occupational exposure can induce in hairdressers, particularly ICD, DNA damage, increase the TNFa levels particularly in ACD and induce allergic sensitization, suggesting a relationship between direct-oxidative DNA damage, TNFalpha production and allergic inflammatory disease.

"Mechanic's hands" are a characteristic cutaneous sign of idiopathic inflammatory myositis. We describe the case of a 61-year-old male patient who was diagnosed with idiopathic polymyositis and non-specific interstitial lung disease in 1999, and three years later developed scaly, fissured hyperkeratotic lesions on the lateral and palmar surfaces of the first three fingers of both hands, with little pruritus. The presence of the anti-Jo-1 antisynthetase antibody in the patient's serum, the finding of skin lesions characteristic of "mechanic's hands" and the patient's other systemic clinical manifestations made it possible to establish the diagnosis of "antisynthetase syndrome."

Sweet's syndrome is associated with haematological malignancy, particularly acute myelogenous leukaemia, but there are few reports of its association with polycythaemia rubra vera. We describe an 85-year-old man with polycythaemia rubra vera who developed Sweet's syndrome and review the literature of this association.

We report a typical case of papular-purpuric "gloves and socks" syndrome (PPGSS) in which primary infection by parvovirus B19 was demonstrated by seroconversion to this virus; parvovirus B19 DNA was also identified by polymerase chain reaction (PCR) methods in the sera of the patient and in the cutaneous biopsy specimen, both taken 4 days after the onset of clinical manifestations. To our knowledge, this is the fourth published case in which parvovirus B19 DNA has been recovered from the skin by PCR. Serologic studies and PCR investigations in cutaneous biopsy for other viruses including herpes simplex virus types 1 and 2, varicella zoster virus, Epstein-Barr virus, cytomegalovirus, and human herpesvirus 6, 7, and 8 were negative. Clinically, our case presented some additional features, which have not been previously described in cases of PPGSS, namely dysuria with vulvar edema and erythema, and unilateral petechial rash on the breast. The histopathologic findings of our case were nonspecific and consisted of an interface dermatitis with slight vacuolar degeneration at the dermoepidermal junction and a superficial perivascular inflammatory infiltrate mostly composed of lymphocytes, with numerous extravasated erythrocytes. We review the cases of PPGSS published in the literature with respect to the different viruses that have been proposed as etiologic agents and conclude that acute infection by parvovirus B19 is the only one that has been adequately proved.

We report two brothers, aged 5 and 2 years, with typical features of congenital erythropoietic porphyria. The elder did not receive medical attention until the age of 2 years, even though his urine had been red almost from birth, and despite severe scarring of the hands and face. The younger brother suffered haemolysis at birth. The uroporphyrinogen III cosynthase (URO IIIS) enzyme activity of red blood cells was 2% and 1.2% in the brothers, and genetic studies showed two different mutations of the URO IIIS gene, C73R and P248Q. The latter is a recently described mutation.

We report a 68-year-old man who had immediate-type heat urticaria with systemic symptoms. Immersing his hand in water at 42 degrees C (heat challenge test) produced an urticarial response, with an increase in the plasma histamine level from 0.26 to 7.64 ng/mL. Administration of oral antihistamines alone did not suppress either the urticarial response or the increase in plasma histamine. However, a combination of antihistamines and desensitization improved the skin lesions and reduced the plasma histamine level. The heat challenge test subsequently provoked a negative response and there was no increase in plasma histamine level 3 months after starting the combination therapy. These results indicate that the histamine level reflected the result of the heat challenge test and the amelioration of the skin eruption.

Five patients with acral chilblains and lupus anticoagulant activity revealed by coagulation analysis are reported. Three patients suffered a systemic lupus erythematosus, and two of them a completely developed antiphospholipid syndrome as well. Another case had chronic cutaneous lupus with only facial discoid lesions, and in the last one the lupus anticoagulant was likely related to a chronic liver infection of hepatitis B virus because she had not erythematous lupus. There are few dermatologic references about chilblain associated to lupus anticoagulant. Certain evidences suggest a pathogenic relation of this findings.

Background: Several patients were observed with a peculiar cutaneous eruption limited to the dorsa of the hands and fingers. Clinically the lesions had some resemblance to those seen in Sweet's syndrome, but biopsy specimens showed severe leukocytoclastic vasculitis., Objective: Our purpose was to characterize this eruption clinically and histologically and compare it with previously described diseases., Methods: Six patients observed since 1977 are described. Skin biopsy specimens were obtained., Results: In six women (age, 41 to 79 years) a symmetric eruption of papules and plaques limited to the dorsa of the radial sides of the hands and first three digits developed. The lesions resembled those of Sweet's syndrome and were associated with fever, sterile culture, blood neutrophil leukocytosis, nonresponse to antibiotic therapy, and rapid response to prednisone. Biopsy specimens showed a severe leukocytoclastic vasculitis., Conclusion: These patients appear to have a distinct entity that we have termed pustular vasculitis of the hands.

In seven winter seasons a young watchmaker was severely disabled by the development of swelling and reddening of the skin, blistering and paraesthesiae affecting his hands. Hospital examination led to a diagnosis of "Raynaud syndrome of undetermined origin". Treatment with corticosteroids was unsuccessful. Not until the young man changed his job did the disorder disappear for good. Investigations at his place of work revealed that the man had inhaled dichloromethane fumes (methylenchloride; CH2Cl2) while cleaning watch parts in a small room that was not ventilated during the winter months. This led to endogenous carboxyneogenesis and subsequently to chronically recurring carboxyhaemoglobinaemia (13%, 10% and 10.7% COHb in three different blood samples). The significance of dichloromethane-induced CO poisoning in the development of dermatological changes is still the subject of controversial discussion.

Superoxide generation by blood monocytes was examined in patients with irritant, nickel, and chromate hand dermatitis. Phorbol myristate acetate stimulated monocytes generated significantly more superoxide in patients with nickel dermatitis, as did patients with hand eczema generally. No significant stimulation of monocyte superoxide generation occurred with either opsonized zymosan or PMA in the presence of excess superoxide dismutase in any of the groups of hand dermatitis. The results indicate a biochemical stimulation of superoxide which may accentuate the immunological damage in the skin that is observed in nickel and perhaps chromate dermatitis.

Systemic sclerosis is characterized by excessive deposition of collagen and other matrix proteins in the skin and internal organs. One hypothesis supports fibroblast stimulation for production of excess amounts of collagen by factors present in the blood or released by cells composing inflammatory tissue infiltrates. Increased numbers of mast cells are present in the involved skin of patients with systemic sclerosis, and histamine has been thought to be a possible mediator of fibrosis in this and other fibrotic conditions. We therefore measured plasma histamine levels in 32 patients with systemic sclerosis and found elevated levels in 18 patients (56%). Elevated plasma histamine levels were more common in patients with diffuse disease (74%), in contrast to limited disease (31%). The degree of clinical activity and the duration of disease could not be correlated with histamine levels.

Motilities of leukocytes in response to bacterial antigens or sera were examined in tissues from patients with palmoplantar pustulosis (PPP). Accelerated migration towards bacterial antigens was detected in the case of Staphylococcus epidermidis in 9 of 19 patients, to Propionibacterium acnes in 5 of 19, to Proteus mirabilis and Staphylococcus aureus in 3 of 19, while no acceleration was found in neutrophils from the controls. A significantly accelerated migration of normal lymphocytes in response to both patients' and control sera was nil. Inhibition of migration of guinea pig peritoneal exudate cells mixed with lymphocytes from PPP patients was detected in 12 out of 14 patients with the addition of S. epidermidis antigen and 8 of 14 with the addition of P. acnes antigen, while no such inhibition was detected in all 7 controls. The accelerated migration of neutrophils and inhibition of macrophages may participate in the development of PPP.

Blood plasma thyroxine, triiodothyronine, thyroxine-binding globulin, and thyrotropic hormone have been radioimmunoassayed in 148 patients with rubromycosis. Reduced function of the thyroid has been detected in 39% of patients. Specific antifungal therapy does not essentially influence the function of the hypophyseal-thyroid system.

The angiogenic capability of peripheral blood mononuclear cells (MNCs) from patients with psoriasis was tested by lymphocyte-induced angiogenesis assay. The study was performed in 36 patients with psoriasis vulgaris, six with generalized pustular psoriasis of the von Zumbusch type, and five with palmo-plantar pustular psoriasis. When patients with psoriasis vulgaris were considered as a whole, no significant differences in the angiogenic capability of their MNCs could be detected, as compared with controls. However, when cases of psoriasis were classified into various types, the differences in angiogenic capability of MNCs became evident. This capability was found to be markedly increased in the active form of psoriasis vulgaris and decreased in the stationary stage of the disease. It was increased in palmo-plantar pustular psoriasis but markedly decreased in generalized pustular psoriasis of the von Zumbusch type.

We studied the effects of tonsillectomy in patients with pustulosis palmaris et plantaris (PPP) and suspected of having focal tonsillar infections which could still be observed more than one year after tonsillectomy. The rate of healing with tonsillectomy, including 6 cases with remarkable effect, was 76%. The clinical findings from which we expect an effect of tonsillectomy are (a) late onset PPP and early tonsillectomy, (b) tonsils with grade I hypertrophy, oozing of pus, and localized dark-redness on the anterior palatine arches, (c) anamnestic tonsillitis, and (d) positive results both at tonsillar provocation and negation tests. From the analyses of pre- and postoperative clinical examinations we found that the preoperative values of serum complement (C3), and neutrophils, lymphocytes and eosinophils in peripheral blood were significantly depressed in the effectively treated group, compared with the 'ineffective' group or the control group.

The effects of acitretin (free acid of etretinate) on the serum lipoprotein pattern and on the fat elimination in serum of 8 patients with psoriasis and 4 with palmo-plantar pustulosis were studied. The drug was given for 12 weeks; the average daily dose was 40 mg. Lipoprotein analyses and an intravenous fat tolerance test (IVFTT) were performed on three occasions (before, after 8 weeks' treatment, as well as 8 weeks after the end of the treatment). Acitretin increased the triglyceride concentration of the very low density lipoproteins by about 50% (p less than 0.02) and reduced the cholesterol of the high density lipoproteins significantly (p less than 0.001), leading to an increased low density/high density lipoprotein cholesterol ratio (p less than 0.02). The IVFTT indicated a lowering of the fat elimination capacity. All changes reverted to the original values after an 8-week wash-out period. The data suggest that the effects of acitretin on the lipoprotein metabolism resemble those of etretinate and isotretinoin.

In 18 ambulant patients with palmoplantar pustulosis low plasma zinc concentrations were observed. During treatment with an all-trans aromatic retinoid (RO-10-9359) the values increased while at the same time the skin condition improved in particular with regard to the pustule formation. The observed low plasma zinc values may in some way be related to pustulosis but not as causal factor.

The relationship between psoriasis and palmoplantar pustulosis (PPP) is uncertain, as is the role of the neutrophil granulocyte in these conditions. In a previous comparative study of the rate of polymorphonuclear leucocyte (PMN) phagocytosis of IgG- and IgG-C3b-coated particles, an increased uptake rate was found in both diseases. Further information on the in vivo activity of PMNs in these conditions may be obtainable by determining the level of lactoferrin (LF) in serum from such patients, since LF serves as a specific marker of the turnover and activity of the circulating pool of neutrophils. In this study on 19 patients with psoriasis and 20 patients with PPP, elevated levels of LF were found in both conditions. In contrast, the levels of lysozyme and beta 2-microglobulin, which are markers of monocyte-macrophage and lymphocyte activity, respectively, were normal. This suggests the selective activation of neutrophils in these disorders. LF was significantly correlated (P less than 0.05 and 0.001, respectively) to the rates of phagocytosis of IgG- and IgG-C3b-coated particles, but not to the chemotaxis of isolated PMNs. There was no correlation between the severity of the disease and the levels of serum LF. The data suggest the increased in vivo activity of neutrophils in psoriasis and PPP.