Search

Background: Cutaneous lupus erythematosus (CLE) is an interferon (IFN) -driven autoimmune skin disease characterized by an extensive cytotoxic lesional inflammation with activation of different innate immune pathways. Aim of our study was to investigate the specific role of Janus kinase 1 (JAK1) activation in this disease and the potential benefit of selective JAK1 inhibitors as targeted therapy in a preclinical CLE model., Methods: Lesional skin of patients with different CLE subtypes and healthy controls ( N = 31) were investigated on JAK1 activation and expression of IFN-associated mediators via immunohistochemistry and gene expression analyses. The functional role of JAK1 and efficacy of inhibition was evaluated in vitro using cultured keratinocytes stimulated with endogenous nucleic acids. Results were confirmed in vivo using an established lupus-prone mouse model., Results: Proinflammatory immune pathways, including JAK/STAT signaling, are significantly upregulated within inflamed CLE skin. Here, lesional keratinocytes and dermal immune cells strongly express activated phospho-JAK1. Selective pharmacological JAK1 inhibition significantly reduces the expression of typical proinflammatory mediators such as CXCL chemokines, BLyS, TRAIL, and AIM2 in CLE in vitro models and also improves skin lesions in lupus-prone TREX1 -/- -mice markedly., Conclusion: IFN-associated JAK/STAT activation plays a crucial role in the pathophysiology of CLE. Selective inhibition of JAK1 leads to a decrease of cytokine expression, reduced immune activation, and decline of keratinocyte cell death. Topical treatment with a JAK1-specific inhibitor significantly improves CLE-like skin lesions in a lupus-prone TREX1 -/- -mouse model and appears to be a promising therapeutic approach for CLE patients., (Copyright © 2020 Fetter, Smith, Guel, Braegelmann, Bieber and Wenzel.)

Lichen planopilaris (LPP) is an inflammatory cicatricial alopecia for which many different therapies are attempted with varying success. The Janus kinase (JAK) inhibitor, tofacitinib, has been shown to be effective in treating the noncicatricial alopecia, alopecia areata. As in alopecia areata, upregulation of interferon and JAK signaling may play a role in LPP. We retrospectively reviewed the cases of 10 patients with recalcitrant LPP who were treated with oral tofacitinib. Patients received oral tofacitinib 5 mg twice or three times daily for 2-19 months as either monotherapy or adjunctive therapy to other ongoing treatments including intralesional triamcinolone, hydroxychloroquine, and tacrolimus ointment. Eight patients had clinical improvement in LPP with tofacitinib as either monotherapy (4/10) or adjunctive therapy (4/10). LPP Activity Index (LPPAI) before and after treatment was measured in seven patients and was significantly different (6.22 before treatment, 3.08 after treatment; p value = .0014). Reduction in LPPAI ranged from 30 to 94%. One patient complained of 10 pound (4.5 kg) weight gain after 12 months on tofacitinib. No other adverse effects were reported. Treatment with oral tofacitinib either as monotherapy or adjunctive therapy can lead to measurable improvement in recalcitrant LPP., (© 2018 The Authors. Dermatologic Therapy published by Wiley Periodicals, Inc.)

Objective: To study the role of serum Monoamine oxidase (MAO) in Lichen planus(LP)., Methods: 82 cases of Lichen planus patients and 35 healthy controls were selected in the investigation. The total serum MAO levels were measured., Results: The levels of serum MAO in Lichen planus patients were significantly higher than those in healthy controls (P<0.01). The severity of Lichen planus was not correlated with serum MAO levels (r =0.4873, t=0.73, p>0.05)., Conclusion: According to the findings, there might be a coincidence of MAO and lichen planus. However, further studies are required to clarify the immunological mechanisms which are responsible for MAO synthesis during immunoreaction.

Background: Lichen planus (LP) is an autoimmune inflammatory disease of the mucocutaneous tissue, whose exact pathological course is not yet understood. Many studies have implicated the role of reactive oxygen species (ROS) and the protective role of antioxidants in several autoimmune skin disorders. In this study, serum levels of antioxidants in patients with LP were determined and compared with those of healthy controls., Methods: In total, 30 patients with LP (mean ± SD age 41.63 ± 13.03), who had never received treatment for their disease, were enrolled; 30 healthy people (aged 41.17 ± 13.24) were recruited as the control group. Serum levels of glutathione peroxidase (GPX), vitamin C, selenium, bilirubin and uric acid were determined., Results: The mean plasma level of vitamin C was significantly lower (P < 0.001) in patients compared with controls. A significant positive correlation was found between selenium and GPX in both patients (Spearman ρ = 0.99, P < 0.001) and controls (ρ = 0.10, P < 0.001)., Conclusions: Lower serum levels of vitamin C in patients with LP indicates that free radicals and the resulting oxidative damage may be important in the pathogenesis of LP lesions., (© The Author(s). CED © 2011 British Association of Dermatologists.)

c-Jun, a component of the activating protein-1 transcription factor family, has been known to play an important role in the control of cell proliferation. It is also suspected to be a critical mediator of tumor promotion. However, investigations of c-Jun activation patterns in inflammatory and inflammatory transforming skin diseases have not been described so far. In this work, we show the c-Jun activation pattern in skin samples of patients with cutaneous lichen planus (LP), squamous cell carcinoma (SCC), psoriasis and normal skin using an immunohistochemical approach and Western blot analysis. In addition, we studied the c-Jun activation pattern in histological samples of three patients in whom LP transformed to SCC. We show that c-Jun is rarely activated in normal skin and psoriasis in contrast to LP and SCC. Our results suggest that c-Jun activation in human skin is involved in (1) proliferation and (2) could potentially participate in the transformation of LP from an inflammatory to a carcinogenic state. Nevertheless, JNK1/2, an important c-Jun activating kinase, was not found to be differentially regulated in LP and SCC compared with normal skin.

Introduction: Lichen planus has been reported in association with liver diseases. Clinical signs such as jaundice may not be reliable indicator of ongoing inflammation or the presence of an ongoing liver disease. Liver function test in spite of its variability may serve as a more reliable indicator of liver disease. The objective of this study is to assess the discriminant power of liver enzymes with lichen planus and control., Methods: Sixty Nigerians with lichen planus (LP group) and 30 patients with other dermatoses control group A) and 30 apparently normal individual (control group B) had their liver enzymes assayed using the automated Hitachi 70 auto-analyzer., Result: There was no a statistically significant difference in the level of liver enzymes between the LP group and controls., Conclusion: Liver enzymes in Nigerian with lichenplanus are generally within normal limits and are comparable to individuals without lichen planus.

Recent studies have provided evidence that a type I interferon (IFN)-driven immune response might play an important role in the pathogenesis of lichen planus (LP), an inflammatory disorder of the skin of unclear etiology. Plasmacytoid dendritic cells in affected skin from LP have been proposed to produce IFN-alpha/beta locally, which leads to the expression of IFN-inducible chemokines such as IP10/CXCL10 in the epidermis. This chemokine recruits chemokine receptor CXCR3-expressing T-lymphocytes into the skin via CXCR3/IP10 interactions. Indoleamine 2,3-dioxygenase (IDO), which degrades tryptophan and suppresses T-cell proliferation, is induced by IFNs and other inflammatory cytokines. We show that type I IFN-mediated skin disorders, such as LP, strongly express IDO in lesional skin. This expression closely correlates to the expression of the highly specific type I IFN marker MxA. We further demonstrate that the IDO+ cells in LP are large myeloid CD11c+S100+CD68(-) dendritic cells. Accordingly, CD11c+ antigen-presenting cells significantly up-regulate IDO gene expression and intracellular IDO protein expression after stimulation with IFN-alpha in vitro. These findings reveal that both proinflammatory and counterregulatory mechanisms are operative in cutaneous lesions of LP. We propose that the balance of these mechanisms may be involved in the pathogenesis of this disorder.

Background: Lichen planus (LP) is an inflammatory skin disease of unknown aetiology. Recently, increased oxidative stress has been implicated in the pathogenesis of various skin diseases such as atopic dermatitis, psoriasis vulgaris and vitiligo., Aim: To evaluate the status of the oxidative stress and antioxidant defence system in patients with LP., Methods: In total, 40 patients with LP (23 men, 17 women; mean +/- SD age 43.27 +/- 1.96 years) and 40 control subjects, matched for age and gender, were enrolled in this prospective study. The exclusion criteria included medication with immunosuppressive agents, history of trauma and surgery, and history of alcohol ingestion for at least 1 month prior to the study. The serum nitric oxide (NO), malondialdehyde (MDA) and superoxide dismutase (SOD) levels and the erythrocyte catalase (CAT) levels were investigated in both groups., Results: Mean +/- SD levels of serum NO (74.60 +/- 17.96 micromol/L) and MDA (18.24 +/- 5.21 micromol/L) in patients with LP were higher than those of the control group (P = 0.007 and P = 0.031, respectively). Serum SOD levels (18.19 +/- 3.71 U/mL) in patients with LP were also higher than in healthy controls (P = 0.002). In contrast, erythrocyte CAT levels (13 557.80 +/- 4134.42 U/kg haemoglobin) were significantly lower in the patient group than in the control group (P = 0.009)., Conclusions: The findings of this study suggest that increased oxidative stress, increased lipid peroxidation and an imbalance in the antioxidant defence system may be involved in the pathogenesis of LP.

The aim of this study was to investigate whether increased oxidative stress occurs in erosive lichen planus of the vulva. Skin biopsies from six patients with untreated, histologically confirmed erosive lichen planus of the vulva were examined immunohistochemically using antibodies against antioxidant enzymes. The protein-bound lipid peroxidation products malondialdehyde (MDA) and 4-hydroxynonenale (4-HNE) and the oxidative DNA damage marker 8-hydroxy-2'-deoxyguanosine (8-OHdG) were investigated. Protein carbonyls as markers of protein oxidation were visualised using the dinitrophenylhydrazone (DNPH) method. Normal vulval tissues from 12 subjects served as controls. In vulval lichen planus tissue the enzymatic antioxidant defence was found to be significantly decreased in the epidermal layers. Furthermore, a significant increase of lipid peroxidation products and oxidative DNA damage was found within the epidermis. Protein oxidation occurred predominantly in the papillary dermis. This is the first study to demonstrate a decreased antioxidant defence and increased oxidative damage to lipids, DNA and proteins in lichen planus. These oxidative modifications point to pathophysiological alterations mainly within the basal cell layers of the epidermis and at the dermoepidermal junction. Further studies are warranted to investigate the potential role of oxidative stress in the development of autoimmunity in this disease.

Serum and tissue angiotensin-converting enzyme (ACE) was measured in 20 patients with lichen planus before and after therapy, and in 20 healthy individuals. Serum and tissue ACE activity was determined by spectrophotometric method using hippuryl-l-histidyl-l-leucine as a substrate. The enzyme activity is expressed in the following units: 1 U corresponds to 1 nmol of hippuric acid released by hydrolysis of hippuryl-l-histidyl-l-leucine per minute and one liter of serum or 50 mg tissue. Before therapy, serum ACE activity was significantly increased in patients with lichen planus (35.9 +/- 2.33 U/L) in comparison to healthy individuals (28.16 +/- 1.7 U/L). Tissue ACE activity was increased in patients with lichen planus (2.24 +/- 0.41 U/50 mg) in comparison to healthy individuals (1.86 +/- 0.16 U/50 mg), but the difference was not significant. After therapy, serum and tissue ACE activity decreased and no significant difference in ACE activity was found. The determination of serum ACE activity may be a good non-specific parameter for the assessment of therapeutic effects.

The number of patients with oral lichen planus increases all over the world. The treatment of this disease is not yet definitive. Although the etiology is not clear until now increasing number of data show relations between the environment and immune-responsiveness. In this study the data (medical history and laboratory test results) of 33 lichen oris patients were processed. The prevalence of diabetes mellitus was much higher in lichen patients, than in persons without lichen oris. Likewise, higher transaminase serum levels in lichen patients were found, and there were two HCV positive cases among them. In contrast to the literary data instead of immune suppressive treatment the immune modulant treatment has been applied: 78% of beta levamisole treated and 90% of interferon alpha treated patients were cured. Only lichen patients without symptoms of general diseases could be stabilized.

The epidermal keratinocytes produce and secrete lipids to maintain the water barrier of the epidermis. To clarify the regulation of epidermal lipid synthesis, we investigated the hormonal effect on the activity of fatty acid synthase (FAS) of the keratinocytes, and the expression of FAS in the human skin. In cultured keratinocytes, the FAS activity, assayed by measuring the oxidation of NADPH, was slightly increased by hydrocortisone or testosterone, but not influenced by thyroid hormone, estrogen, progesterone or insulin. In immunohistochemical study of normal human epidermis, FAS was expressed strongly in the stratum granulosum and moderately in the uppermost layer of the stratum spinousum (SS), suggesting that fatty acid synthesis may increase during normal epidermal differentiation. In inflammatory disorders, such as psoriasis, lichen planus, and atopic dermatitis, FAS was also expressed in the lower SS and the stratum basale (SB), resulting in strong staining in the whole layers of the epidermis. Remarkable increase of FAS expression was only observed in the lower SS and the SB. Therefore, the activity of FAS in the epidermis may be regulated in the lower SS and the SB by local inflammation rather than by circulating hormones. In other components of the skin, FAS was strongly expressed not only in adipose tissue and sebaceous glands, which are known as active sites of lipid synthesis, but also in sweat glands, suggesting that the sweat glands can synthesize abundant fatty acids de novo.

Lichenoid lesions of the skin are characterized by a band-like dermal inflammatory infiltrate and structural alterations of the basement membrane (BM). The etiopathogenesis of these lesions, of which lichen planus (LP) is perhaps the prototypic example, is unknown. Acute cases of LP are accompanied by the destruction of epidermal BM, degeneration of basal keratinocytes with loss of tonofilaments and hemidesmosomes, vesicular alterations, and even blister formation. Chronic LP is characterized by hyperkeratosis and acanthosis in the epidermis, fibrosis, and dense infiltrate in dermis. We found that acute LP lesions are characterized by uneven or absent immunostaining for laminin-5, laminin-1, and collagen type IV. Distribution and activity of gelatinases matrix metalloproteinase (MMP)-9 and MMP-2, and a specific inhibitor of MMP-2, tissue inhibitor of metalloprotein-2, were analyzed. The expression and activity of MMP-2 were increased, whereas tissue inhibitor of metalloprotein-2 expression was weak in the involved areas during the acute phase of LP. Moreover, we demonstrated in vitro that MMP-2 is directly capable of digesting laminin-5 gamma 2 chains to yield a 80-kd fragment. We also observed a weak or absent staining of all examined integrin receptors in the acute LP lesions. In chronic lesions, the staining of BM components was similar to normal controls. In these sections, normal expression of gelatinases and inhibitor was observed. There was, however, up-regulation and altered polarity of integrin receptors. These results indicate a link between overexpression of gelatinases, BM disruption, and altered integrin expression. In LP, the digestion of BM by MMP-2 may contribute to the pathogenesis by inducing altered integrin expression in basal keratinocytes and ultimately blister formation.

A prospective clinical investigation of 45 patients with lichen planus (LP) demonstrated a significant association between LP and chronic hepatitis C. Anti-hepatitis C virus (HCV) antibodies were found in 17 (37.8%) of the 45 LP patients. This was significantly higher than in the controls. This higher prevalence of anti-HCV antibodies was found equally in both male and female patients in the three types of LP; cutaneous only type, mucous only type, and both cutaneous and mucous type. Most of the patients with positive anti-HCV antibodies had abnormal values of transaminase enzymes and/or a past history of chronic hepatitis. Histological and immunohistological investigations of three cases with LP and chronic hepatitis C demonstrated some morphologic similarities between these two diseases. Histopathologic findings of both LP and chronic hepatitis C were based on a T lymphocytic infiltrate with keratinocyte or hepatocyte damage. The degrees of infiltrating cells positive to UCHL-1, MX-panB, Leu-7, and human leukocyte antigen (HLA)-DR antibodies in the chronic hepatitis C lesions seemed to be similar to those in the LP lesions. These results may support a possible relationship between LP and chronic hepatitis C and the hypothesis that LP may be associated with chronic liver diseases as a result of a cytotoxic attack on the hepatocytes.

In order to gain insights into the dynamics of mast cell subpopulations in normal and diseased skin, a novel enzyme-histochemical double and triple staining method was employed that allowed the detection of metachromasia (toluidine blue) and the mast cell proteases tryptase and chymase within the same cell. Cryostat sections were used of skin biopsies from the following specimens: normal skin (N = 4), psoriasis (N = 13), atopic eczema (N = 7), lichen planus (N = 6), interferon alpha 2a injection sites (N = 1) of a leukemic infiltrate and corresponding normal skin of the same patient before and after treatment. (i) Equal numbers of tryptase- and chymase-positive mast cells (MCTC) were obtained in all normal and diseased specimens in papillary and reticular dermis, with threefold increases around appendages. (ii) Tryptase-positive mast cells (MCT) were absent in normal skin, but were markedly increased in a disease-specific pattern within the papillary dermis, the inflammatory infiltrate and around appendages. (iii) Marked increases of MCT were also noted at interferon injection sites within the leukemic infiltrate, but not in the normal skin of the same patient. These data suggest that disease-dependent mast cell dynamics involve only MCT in cutaneous inflammation and that MCT numbers are controlled by distinct, disease-specific local tissue factors.

The dermal elastic fiber network was studied in specimens from five patients with lichen ruber planus, using a standard elastin staining procedure (orcein), results being compared with those for the elastin-associated microfibrillar network stained using anti-fibrillin antibodies in an immunofluorescence and an avidin-biotin-peroxidase complex technique. Additional specimens of healed apparently normal skin were taken from two of the patients. Orcein-stained fibers were scarce or absent in the inflammatory zone in all the lesions. In contrast, an extensive fibrillin immunoreactive network was present in the papillary zone in all the specimens, in a pattern similar to that of normal skin. In specimens from healed lesions of lichen ruber planus, dermal orcein-stained fibers were present in the papillary dermis. The findings indicate that the amorphous component of elastic fibers is destroyed during the acute phase of lichen ruber planus. Hypothetically, the elastolysis is caused by elastases released from macrophages known to be present in the lichenoid infiltrate. In contrast, the fibrillin fiber network seems to be less or not at all affected by proteolytic events during the inflammatory phase of lichen ruber planus.

Phenylethanolamine N-methyltransferase (PNMT)-like immunoreactivity has been found in psoriatic skin and in this study, PNMT-like immunoreactivity was investigated in the involved and uninvolved skin of six patients with lichen planus and four patients with lichen simplex. No PNMT immunoreactivity was observed in these diseases. Studies were carried out using cultured fibroblasts from two patients with psoriasis from uninvolved and involved areas of skin and from two controls using antibodies to PNMT, as well as antibodies to the chemical messengers somatostatin, substance P, parathyroid hormone and peptide histidine isoleucine amide. No immunoreactivity to these substances was found, and fibroblasts are unlikely to be the cellular origin of the PNMT-like immunoreactivity as seen in psoriatic skin.

An histoenzymological study (including oxidative enzymes, diaphorases, acid and alkaline phosphatases and naphtolesterases) of 41 biopsy and operation specimens revealed interesting factors in the diagnosis of some lesions of the buccal mucosa, and also of cysts and ameloblastomas of the jaw. When compared with normal buccal mucosa and epidermis, the enzymatic activities found in the oral lesions, fell into three different types. In non dysplasic leukoplakia, enzymatic activities were found that were similar to those of the epidermis (high oxidative activities, particularly prominent in basal cells and in the granular layer and esterasic activity beneath the keratinised layer). In lichen planus, some vacuolized or necrotic basal cells occurred which lacked enzymatic activity. In the upper layers, the distribution of the enzymes was irregular. In severe dysplasia and epidermoid carcinoma, numerous variations of oxidative, esterasic and acid phosphatase activities were seen from one cell to another. Among the lesions of the jaws, radicular cysts as well as dentigerous cysts, had low enzymatic activities, similar to those of normal buccal epithelium. The epidermoid cysts (keratocysts), because of their highly differentiated keratinization, like leukoplakia, had the same enzymatic activities as epidermis. The enzymatic activities of common ameloblastoma differed from those of malpighian tissues (low oxidative activities without decreasing gradient). Besides round epithelial nests, the stroma showed a high and widespread alkaline phosphatase activity, which indicated a low degree of odontogenic induction. Thus, this peculiar stromal activity may be useful in differentiating between cystic epidermoid varieties of ameloblastoma and the other epidermoid cysts of the jaws.

Activity of the enzyme acid alpha-naphthyl acetate esterase (ANAE) in T lymphocytes and histiocytes in cutaneous tissue sections of patients with histologically confirmed lichen planus, chronic discoid eczema and mycosis fungoides was compared with results obtained using an in situ immunohistochemical technique employing an antiserum against the human T lymphocyte surface antigen (HTLA). In lichen planus and chronic discoid eczema, most of the cells in the cutaneous infiltrate exhibited both positive ANAE activity and the presence of HTLA. In mycosis fungoides, cells identified as T lymphocytes by the presence of HTLA often showed no ANAE activity. ANAE activity appears to be a useful marker of T lymphocytes in benign cutaneous infiltrates but is less reliable in labelling abnormal T cells.

Untreated cases of lichen planus have been studied by histochemical techniques. The acid phosphatase reaction in the transitional zone has been quantitatively estimated and compared with the adjacent relatively normal epidermis. It was found that despite a thickened and accentuated granular layer as seen by routine histological methods there was a marked reduction in the intensity of the acid phosphatase reaction. The glucose-6-phosphate dehydrogenase reaction was marked in the upper layers of the epidermis in active lesions of lichen planus. This is similar to psoriasis, but different from normal human epidermis. The suggestion by other authors that lichen planus is an inborn error of metabolism is discussed. The dendritic cells of the epidermis as studied by the ATPase reaction are virtually absent in regions of active lichen planus and the possible significance of this is mentioned. The horny layer gives a dense reaction for phospholipids in lichen planus and this is similar to psoriatic keratin. The significance of this finding is considered.

It is now well established that epidermis, like many other tissues, contains a phospholipase A2 that is responsible for the initiation of the arachidonic acid cascade. Here we report that human epidermis also contains a second, quite distinct enzyme of the phospholipase A2 group, which is unique in its extreme activity against phospholipids in true solution. It also differs from the classic cutaneous enzyme in that (a) its activity is not reduced by pretreatment of the skin with corticosteroids in vivo nor by treatment of the epidermal homogenate with alkaline phosphatase in vitro, and (b) its activity is reduced, rather than increased, in the lesions of inflammatory diseases such as psoriasis. The enzyme seems to occur mainly in fully differentiated keratinocytes, its level being low in the basal cell layer of epidermis and in keratinocytes cultured in vitro. On the basis of these observations, we suggest that this new phospholipase A2 is responsible for the degradation of phospholipids that accompanies the terminal keratinization process.

The phenomenon of lichenoid eruptions following medication with antimalarial, anti-arthritis and antibacterial medication is well documented in the literature. We report here the first case to be described as a result of anti-arthritis treatment with penicillamine, together with some biochemical studies of the effect of this compound on the enzyme glucose-6-phosphate dehydrogenase.

Cotton et al [1] comparing glucose-6-phosphate dehydrogenase (G-6-PD) activity in biopsies from patients with lichen planus (LP) with that in normal skin suggested that LP might be associated with a congenital abnormality of the enzyme in the skin. Ryan et al. [7] were unable to confirm these results. It is known that individuals with erythrocyte G-6-PD deficiency show a similar decrease of the enzyme in the skin [2] and that skin biopsies can be used to diagnose favizm [3]. The increased incidence of LP in the tropics [6, 8] coincides with the prevalence of erythrocyte G-6-PD deficiency in the same geographical region. The semi-quantitative method of Motulsky did not reveal any difference of erythrocyte G-6-PD activity between patients with LP and control subjects [5]. The present study reports the results obtained with a more sensitive method of erythrocyte G-6-PD determination in a group of Africans with LP. Thirty Nigerian patients with typical clinical picture of LP (23 men and 7 women), aged 15--45 were studied. Control 30 subjects were matched for age, sex and tribe and included persons suffering from scabies and mild pyogenic and superficial mycotic infections. The activity of the erythrocyte G-6-PD was determined at 37 degrees C using the WHO method [9]. Normal values for Northern Nigerians are 1200 +/- 234 mu/1010 red cells. The results (Fig. 1) show a decrease of the erythrocyte G-6-PD activity in patients with lichen planus (P less than 0.01). No relationship between erythrocyte G-6-PD activity and extensiveness, activity or age of onset of the skin lesions was found. The finding of decreased erythrocyte G-6-PD activities in patients with LP in an area where an increased incidence of this skin disease coincides with higher frequency of favizm might suggest a biochemical overlap between these two conditions. Holzmann et al [4] have suggested that the reverse situation of mutual exclusiveness exists between G-6-PD deficiency and psoriasis. In regions with high frequency of G-6-PD defiency psoriasis is uncommon.

Various epidermal enzymes and cofactors were measured in patients with lichen planus and in healthy controls with the aid of Lowry's microtechniques, including enzymatic cycling. The steady-state levels of the nicotinamide adenine dinucleotides NAD and NADP were decreased and this was evident even in areas still free from lesions. The oxidized and reduced portions of NAD were altered indicating changed equilibria of NAD dependent dehydrogenases. Reduced NADP was more tightly controlled at the normal level which is regarded as evidence of an unaltered biosynthetic potential in this disease. In conjunction with earlier data the results indicate a preserved glycolytic and pentose shunt activity while the mitochondria display signs of dysfunction.

Serum activities of ACE were investigated in 40 patients with dermatological disease and in nine patients with sarcoidosis. The method of Cushman and Cheung, modified according to Lieberman, was used. Both sarcoidosis patients and patients with dermatological diseases showed marked elevations of ACE-activity. The increase in ACE-activity might result from inflammation and immunological events.

Enzymic activities and cofactor levels in the epidermis are reviewed with special regard to psoriasis and the papulosquamous disorders lichen simplex and lichen planus. The metabolism of nicotinamide adenine dinucleotide phosphate and its dependent pathways seems to deviate in psoriasis from that in the contrasted dermatoses, in normal skin in health and in skin during the process of wound healing. The mitochondrial function also differs between psoriatic and normal skin. In some conditions in psoriasis this function cannot be seen to deviate from normality, however. The regulation and control of mitochondrial function in psoriasis might be another area in which future investigations may yield significant information on the pathophysiology in this skin disease.

The apparent Michaelis constant (Km) for glucose-6-phosphate of the enzyme glucose-6-phosphate dehydrogenase has been measured in extracts prepared from biopsies of normal human skin and from both affected and apparently normal skin of patients with lichen planus. No differences of Km were found and starch gel electrophoresis of extracts from lichen planus lesions and normal controls showed similar patterns when stained for glucose-6-phosphate dehydrogenase activity. These results do not support the view that lichen planus is an inborn error of metabolism in which the structure of glucose-6-phosphate dehydrogenase of skin is affected.

A histoenzymological study was carried out on 41 tissue specimens removed at biopsy and for surgical operations of the following lesions: benign hyperkeratosis, lichen planus, severe epithelial dysplasia, carcinoma in situ, epidermoid carcinoma, radicular cyst, odontogenic keratocyst and ameloblastoma. The purpose of this study was to study some possibly significant variations in levels of activities of oxidative enzymes, diaphorases, acid phosphatases and Naphthol esterases in such lesions (normal oral mucosa and epidermis serving as controls). In the lesions of the oral mucosa, these histoenzymological variations were not sufficiently characteristic to contribute to histological diagnosis. In lichen planus, some vacuolated or necrotic basal cells lacked enzyme activities, whereas in the upper layers, enzyme activities were irregularly present. Benign hyperkeratosis showed enzymatic activities similar to those of the normal epidermis, namely high oxidative activities particularly prominent in basal cells and in granular layer, and esterase activity beneath the keratinized layer. In severe epithelial dysplasia, carcinoma in situ and epidermoid carcinoma, numerous variations of activities of oxidative enzymes, esterases and acid phosphatase were seen from one cell to the other. In cystic diseases of jaws, enzymatic activities were equally nonspecific in the epithelial lining of the radicular cyst and the odontogenic keratocyst (activities similar to those of normal oral epithelium and epidermis, respectively). But in common ameloblastoma, there was diffuse uniformly low oxidative enzymatic activities in the epithelium and high widespread activity of alkaline phosphatase in the stroma. The latter may be useful in differentiating the cystic acanthomatous variety of ameloblastoma from odontogenic keratocysts of the jaws.