Drug Interactions in Dermatology: What the Dermatologist Should Know

A drug interaction is a process by which a drug or any other substance interacts with another drug and affects its activity by increasing or decreasing its effect, causing a side effect or producing a new effect unrelated to the effect of either. Interactions may be of various types-drug-drug interactions, drug-food interactions, drug-medical condition interactions, or drug-herb interactions. Interactions may occur by single or multiple mechanisms. They may occur in vivo or in vitro (pharmaceutical reactions). In vivo interactions may be further subdivided into pharmacodynamic or pharmacokinetic reactions. Topical drug interactions which may be agonistic or antagonistic may occur between two drugs applied topically or between a topical and a systemic drug. Topical drug-food interaction (for example, grape fruit juice and cyclosporine) and drug-disease interactions (for example, topical corticosteroid and aloe vera) may also occur. It is important for the dermatologist to be aware of such interactions to avoid complications of therapy in day-to-day practice.     

Comparative therapeutic evaluation of different topicals and narrow band ultraviolet B therapy combined with systemic methotrexate in the treatment of palmoplantar psoriasis

Background:

The incidence of uncomplicated psoriasis is 1–3% in the general population. The involvement of palm and sole is seen in 7–14.5% of cases. There are different topicals and systemic therapies available for treating the case of psoriasis but none is satisfactory for longer duration.

Aim:

The study involved the comparative therapeutic evaluation of the different topical regimens and narrow band ultraviolet B (NB-UVB) therapy in combination with systemic methotrexate.

Materials and Methods:

The study was held in out-patient department of Skin, VD and Leprosy of B.R.D. Medical College, Gorakhpur, from July 2007 to December 2008. The group included 98 new cases of palmoplantar psoriasis. These cases were divided into eight groups according to the eight regimens involved in the study. The severity of psoriasis was assessed by the ESIF (erythema, scaling, induration and fissuring) score.

Results:

The study showed that all the regimens had significant response rates. The combination of NB-UVB with systemic methotrexate had maximum response rate (64.85±4.52%) that was statistically significant (paired “t” at 16d.f. = 33.329, P<0.001) with minimum number of recurrences after stopping the treatment. The combination of halobetasol ointment with systemic methotrexate also had significant response rate (paired “t” at 19d.f. = 13.5183, P<0.001) but had maximum number of cases with recurrence (70%) after stopping the treatment.

Conclusion:

These results suggest that the combination of every regimen with systemic methotrexate resulted in an early and a good improvement in the quality of life of patients suffering from psoriasis. It also shows that NB-UVB in combination with systemic methotrexate is more efficacious and has minimum recurrence rate and side effects in the treatment of palmoplantar psoriasis.     

Lyme Borreliosis and Skin

Lyme disease is a multisystem illness which is caused by the strains of spirochete Borrelia burgdorferi sensu lato and transmitted by the tick, Ixodes. Though very commonly reported from the temperate regions of the world, the incidence has increased worldwide due to increasing travel and changing habitats of the vector. Few cases have been reported from the Indian subcontinent too. Skin manifestations are the earliest to occur, and diagnosing these lesions followed by appropriate treatment, can prevent complications of the disease, which are mainly neurological. The three main dermatological manifestations are erythema chronicum migrans, borrelial lymphocytoma and acrodermatitis chronica atrophicans. Many other dermatological conditions including morphea, lichen sclerosus and lately B cell lymphoma, have been attributed to the disease. Immunofluorescence and polymerase reaction tests have been developed to overcome the problems for diagnosis. Culture methods are also used for diagnosis. Treatment with Doxycycline is the mainstay of management, though prevention is of utmost importance. Vaccines against the condition are still not very successful. Hence, the importance of recognising the cutaneous manifestations early, to prevent systemic complications which can occur if left untreated, can be understood. This review highlights the cutaneous manifestations of Lyme borreliosis and its management.     

Nephrogenic systemic fibrosis: a brief review

Nephrogenic systemic fibrosis is a fibrosing disorder of the skin that develops in patients with advanced renal failure. It mostly presents with progressive hardening or induration of the skin of the extremities. Systemic involvement is also known to occur in this entity. Exposure to gadolinium contrast for radiological evaluation has been identified as the offending agent. The condition is progressive and can be seriously disabling. Therapeutic options are limited and not rewarding in majority of the cases. Awareness of this entity is important so that proper precautionary measures can be taken at the earliest to ameliorate the condition.     

Delivery of Amphotericin B for Effective Treatment of Candida Albicans Induced Dermal Mycosis in Rats via Emulgel System: Formulation and Evaluation

Background:

Amphotericin B (AmB) is among the gold standard antifungal agents used for the treatment of the wide range of fungal infections. However, the drug has various side- effects. Transdermal approach for the delivery of drug is one of the accepted and convenient modes of drug delivery. Aim: The current work was designed to formulate and to evaluate the AmB emulgel system.

Materials and Methods:

In the preparation of AmB emulgel, Carbopol 930 was used as a gel in this study. The formulation was evaluated for viscosity, spreadability, drug content, drug release and in vitro and in vivo antifungal testing.

Results:

AmB emulgel was found to penetrate skin effectively and without any irritation. Further, in vivo studies revealed effective therapeutic potential against Candida albicans induced dermal mycosis. Conclusions: The current work, for the first time, revealed effective delivery of AmB across the skin.     

A Curious Case of Sweating Blood

Hematohidrosis is a very rare condition in which an individual sweats blood. It may occur in an individual who is suffering from extreme levels of stress. Various causative factors have been suggested like component of systemic disease, vicarious menstruation, excessive exertion, psychogenic, and unknown causes. Fear and intense mental contemplation are the most frequent causes. It may also occur in bleeding disorders. We here report a case where bloody sweat was discharged from the forehead, face, and body episodically in a 12-year-old healthy girl with no bleeding disorder or any other underlying cause. All investigations done were within normal limits, except low intelligent quotient and loss of insight. The patient was given atropine sulphate transdermal patch with marked improvement in severity.     

OXIDATIVE STRESS IN EXPERIMENTAL VITILIGO C57BL/6 MICE

Aim:

To evaluate whether oxidative stress is implicated in melanocyte damage in vitiligo.

Background:

Vitiligo is a complex disorder characterized by gradually enlarging areas of depigmentation. A new unifying hypothesis for the etiology of this pigment disorder is proposed, in which we postulate that the final destruction of melanocytes in vitiligo results from a cascade of reactions initiated by a disregulation of melanogenesis, as the result of a breakdown in free radical defense.

Methods:

We evaluated 18 vitiligo mice and 12 controls that were age matched. Parameters of oxidative stress such as catalase (CAT), superoxide dismutase (SOD), and plasma malondialdehyde (MDA) were measured by spectrophotometry.

Results:

MDA levels in vitiligo mice were significantly higher than in controls (P < 0.001). CAT, SOD, and glutathione peroxidase (GPx) activities in mice were significantly lower than controls (P < 0.05 and P < 0.001, respectively).

Conclusion:

Our results confirmed that oxidative stress plays an important role in the pathogenesis of vitiligo. Melanocyte damage in vitiligo might be linked to generalized oxidative stress. This study is the first report on antioxidant parameters in experimental vitiligo mice.     

COMPARISON OF THE ACTIVITIES OF FOUR ANTIFUNGAL AGENTS IN AN IN VITRO MODEL OF DERMATOPHYTE NAIL INFECTION

Background:

Onychomycosis is a difficult condition to treat and cure rates are disappointing. Moreover fungicidal action of antifungal agents in NCCLS assays and their rapid accumulation in nails in vivo are not compatible with the duration of treatment.

Aims:

This study aimed to find the effectiveness of 4 different antifungal agents in an in vitro model with some similarities to in vivo conditions.

Materials and Methods:

Strains of Trichophyton rubrum I-III, Trichophyton mentagrophytes (usual form), Trichophyton mentagrophytes 73, Epidermophyton Flucosom, Microsporum Canis, and Trichophyton Schoenleini which were isolated from the nails of patients, were hired. Inocula suspensions were prepared from 7 to 14 day-old cultures of dermatophytes. Antifungal agents including fluconazole, ketoconazole, terbinafine, and griseofulvin were obtained as standard powders. For each antifungal agent, initial MIC was calculated by registering the optical density for 10 two-fold serially diluted forms which was incubated with diluted fungal suspensions with RPMI 1640. Human nail powder inoculated with different strains and incubated in RPMI 1640 and different concentrations of antifungal drugs for 4 weeks. Final MIC at different steps of 1, 2, 3 and 4 weeks were investigated.

Results:

The final MIC that resulted from the incubation of dermatophytes with nail powder was much more than the initial which was concluded from conventional MIC assay. Terbinafine had the lowest rate of initial and final MICs.

Conclusion:

The model described here may present more similar conditions to clinical fungal infections; therefore the results such as MIC may be more helpful for hiring the most effective antifungal agent.     

Violaceous Maculopapular Rash in a Newborn: Congenital Rubella Syndrome

Congenital rubella syndrome involves a configuration of systemic and cutaneous manifestations in a neonate due to in utero infection caused by the rubella virus. The case of a preterm neonate with blueberry muffin lesions and classical as well as rare systemic features of congenital rubella syndrome is reported.     

Serum Prolactin Levels in Psoriasis and its Association with Disease Activity: A Case-Control Study

Background:Psoriasis is a T-cell-mediated autoimmune chronic skin disorder in which an environmental factor, perhaps a viral antigen, induces T cells to produce cytokines. These cytokines stimulate keratinocyte proliferation and production of antigenic adhesion molecules in the dermal blood vessels. Several mediators and hormones have been implicated in keratinocyte hyperproliferation and among these hormones, prolactin (PRL) has been found to have an effect on epithelial cells, lymphocytes and keratinocytes, thus an effect on the etiopathogenesis of psoriasis.Aim:The present study was designed to compare serum PRL levels in psoriatic patients with a control group.Results:Serum PRL levels were significantly increased in patients as compared to the control group (P value: 0.002). There was a positive correlation between pretreatment serum PRL levels and PASI score (r value: 0.379; P value: 0.003). An insignificant association was found between the pretreatment PRL level and serum PRL level after treatment (P value: 0.22). Also, a negative correlation between the duration of psoriasis and serum PRL was seen (r value: -0.008; P value: 0.954).Conclusion:PRL may have a role to play in the etiopathogenesis of psoriasis. However, further studies with large sample size should be carried out so as to validate this hypothesis.     

Role of In Vivo Reflectance Confocal Microscopy in Determining Stability in Vitiligo: A Preliminary Study

Background:

Vitiligo is an acquired pigmentary disorder. In vivo reflectance confocal microscopy (RCM) reproducible imaging technique has already been reported to be useful in the diagnosis of other skin diseases.

Objective:

To define RCM features of vitiligo on different clinical stages.

Materials and Methods:

A total of 125 patients with a clinical diagnosis of vitiligo were included in this study. After informed consent, lesional skins of those vitiligo patients were characterized by using RCM. Five patients with inflammatory cell infiltration observed at the edge of skin lesions and another 5 patients without inflammatory cell infiltration were selected. Biopsies were performed at same sites of the RCM examination areas for histological and immune-histological analysis.

Results:

In the active stage of vitiligo, the RCM examination revealed that the bright dermal papillary rings presented at the dermoepidermal junction level in normal skin lost their integrity or totally disappeared, border between vitiligo lesion and normal skin became unclear, and highly refractile cells that referred to infiltrated inflammatory cells could be seen within the papillary dermis at the edge of the lesions. In the stable stage of vitiligo, the RCM showed a complete loss of melanin in lesional skin and a clear border between lesional and normal skin.

Conclusion:

A simple clinical examination with RCM may reliably and efficiently allow evaluation of the stability status of vitiligo lesions.     

ALOPECIA AREATA AND AUTOIMMUNITY: A CLINICAL STUDY

Alopecia areata (AA) frequently occur in association with other autoimmune diseases such as thyroid disorders, anemias and other skin disorders with autoimmune etiology. Despite numerous studies related to individual disease associations in alopecia areata, there is paucity of literature regarding comprehensive studies on concomitant cutaneous and systemic diseases. The present study has been designed to determine if there is a significant association between alopecia areata and other autoimmune diseases. This study covers 71 patients with the diagnosis of alopecia areata as the case group and 71 patients with no evidence of alopecia areata as the control group. Among the cutaneous diseases associated with AA, atopic dermatitis (AD) showed maximum frequency with an O/E ratio of 2.5, which indicates that it is two to three times more common in patients with alopecia areata. In our study, thyroid disorders showed the highest frequency with on O/E ratio of 3.2 and a P value of 0.01, which is statistically highly significant. Among the thyroid disorders, hypothyroidism was the most frequent association (14.1%) in our study. Since systemic involvement is not infrequent in patients with alopecia areata, it is imperative to screen these patients for associated disorders, particularly atopy, thyroid diseases, anemias and other autoimmune disorders, especially if alopecia areata is chronic, recurrent and extensive.     

INCREASED INCIDENCE OF TUBERCULOSIS IN PATIENTS OF SYSTEMIC SCLEROSIS ON DEXAMETHASONE PULSE THERAPY: A SHORT COMMUNICATION FROM KASHMIR

Background:

Systemic sclerosis is a multi-systemic autoimmune disorder affecting predominantly the skin, lungs, gut and kidneys.

Purpose:

To report the increased incidence of tuberculosis in patients of systemic sclerosis on dexamethasone pulse (DP) therapy.

Methods:

Forty-seven patients of systemic sclerosis were included in the study. After taking a complete history and doing a detailed physical examination, the patients were submitted to a battery of investigations including complete hemogram (CBC) with erythrocyte sedimentation rate (ESR(F)), Chest X-ray CXR (PA view) Mantoux test and urine analysis. CBC, ESR and urine examination was done monthly and CXR were repeated six-monthly.

Findings:

Seven patients on DP therapy developed genitourinary tuberculosis. Four had pulmonary tuberculosis. One patient developed tubercular lymphadenitis, one patient succumbed to miliary tuberculosis.

Conclusion:

There is an increased incidence of tuberculosis amongst patients of systemic sclerosis on DP therapy.

Limitation of the Study:

There was no control group of systemic sclerosis patients not on DP therapy to rule out the confounding effect of the disease per se predisposing to tuberculosis as all our patients as a matter of routine were put on steroid pulse. Also, the increased incidence of tuberculosis was detected incidentally while on monthly follow-up.     

Alterations in Lipid Metabolism and Antioxidant Status in Lichen Planus

Background:

Lichen planus (LP), a T-cell-mediated inflammatory disorder, wherein inflammation produces lipid metabolism disturbances, is linked to increase in cardiovascular (CV) risk with dyslipidemia. Increased reactive oxygen species and lipid peroxides have also been implicated in its pathogenesis.

Aim and Objective:

The aim of the study was to evaluate the status on lipid disturbances, oxidative stress, and inflammation in LP patients.

Materials and Methods:

The study was initiated after obtaining Institutional Ethics Committee permission and written informed consent from participants. The study included 125 patients (74 LP patients and 51 age and sex-matched controls) visiting the outpatient clinic in the dermatology department of our hospital. Variables analyzed included lipid profile, C-reactive protein (CRP), malondialdehyde (MDA), and catalase (CAT) activity.

Results:

Analysis of lipid parameters revealed significantly higher levels of total cholesterol (TC), triglycerides, and low-density lipoprotein cholesterol (LDL-C) along with decreased levels of high-density lipoprotein cholesterol (HDL-C) in LP patients as compared to their respective controls. LP patients also presented with a significantly higher atherogenic index that is, (TC/HDL-C) and LDL-C/HDL-C ratios than the controls. A significant increase in CRP levels was observed among the LP patients. There was a statistically significant increase in the serum levels of the lipid peroxidation product, MDA and a statistically significant decrease in CAT activity in LP patients as compared to their respective controls. A statistically significant positive correlation (r = 0.96) was observed between serum MDA levels and duration of LP whereas a significantly negative correlation (r = −0.76) was seen between CAT activity and LP duration.

Conclusion:

Chronic inflammation in patients with LP may explain the association with dyslipidemia and CV risk. Our findings also suggest that an increase in oxidative stress and imbalance in the antioxidant defense mechanisms in LP may play a role in the pathogenesis of LP.     

Plasma Levels of Interleukin-17, Interleukin-23, and Transforming Growth Factor-β in Sudanese Patients with Vitiligo: A Case-Control Study

Background:

Vitiligo is the most common pigmentary skin disorder. It is a multifactorial polygenic disease with epidermal melanocyte destruction. The cytokines profile found in vitiliginous patients was not fully elucidated.

Aims:

We sought to assess the autoimmune nature of vitiligo by comparing plasma levels of interleukin (IL)-17, IL-23, and transforming growth factor beta (TGF-β) in adult Sudanese vitiligo patients with matched control individuals.

Subjects and Methods:

Case-control study was conducted in Khartoum Dermatologic Teaching Hospital, in the period between July and December 2013. The cases were 42 adult Sudanese vitiligo patients matched with 43 control individuals. The cytokines were measured in the plasma by the quantitative “sandwich” ELISA.

Results:

Patients showed a significant lower median (25–75^th inter-quartile) of TGF-β than control (0.042 [0.041–0.044] vs. 0.047 [0.042–0.049]; P ≤ 0.001). Both IL-17 and IL-23 showed no significant difference between cases and controls. IL-17 showed a significant inverse relationship when correlated with TGF-β (r = −0.24; P = 0.026) while showing direct relationship when correlated with age (r = 0.28; P = 0.009).

Conclusion:

The positive findings detected in this study coincide with the important immunoregulatory role of the TGF-β, and support the autoimmune nature of the disease.     

The Evaluation of the Impact of Age,Skin Tags,Metabolic Syndrome,Body Mass Index,and Smoking on Homocysteine,Endothelin-1, High-sensitive C-reactive Protein,and on the Heart

Background:

Skin tags (STs) are small, pedunculated skin-colored or brown papules that occur around any site where skin folds occur. The literature is short of comprehensive and controlled clinical studies aimed to evaluate the atherogenic risk factors in patients with STs.

Aim of Work:

The aim of this study is to evaluate the impact of age, STs, metabolic syndrome (METs), body mass index (BMI), and smoking on homocysteine (Hcy), endothelin-1 (ET-1), high-sensitive C-reactive protein (Hs-CRP), and on cardiovascular diseases.

Materials and Methods:

This study included 30 cardiac patients with STs, 30 non-cardiac patients with STs, and 30 healthy controls with neither heart disease nor STs. History of smoking, measurement of height, weight, BMI, waist circumference (WC), blood pressure, STs number, color, acanthosis nigricans, estimation of serum level of fasting glucose, triglycerides (TGs), cholesterol, high-dense lipoproteins (HDL), Hcy, ET-1, Hs-CRP, and the presence of the METs were elicited in the three groups.

Results:

Regarding the Hcy, ET-1, and Hs-CRP, the cardiac-STs group showed the highest levels and the control group showed the least (P < 0.001). The percents of patients with METs were 56.7% in the cardiac-STs, 40% in the non-cardiac-STs, and 0% in the control group (P < 0.001). Mean BMI exceeded the limit of obesity in the cardiac-STs group (30.9 ± 3.9) and the non-cardiac-STs group (32.6 ± 6) and was normal in the control group (24.7 ± 2.8). Hyperpigmented STs were present in 66.7% of the cardiac-STs group. Multivariate regression analysis for the independent effectors on Hcy level were the presence of STs (P < 0.001), METs (P = 0.001), and BMI (P = 0.024). Regarding ET-1, the effectors were the presence of STs and METs (P = 0.032). For Hs-CRP, effectors were the presence of STs (P < 0.001) and smoking (P = 0.040). Multivariate logistic regression of the predictors of cardiac disease showed that the independent predictors of the occurrence of cardiac disease were BMI (P < 0.001), STs (P = 0.002), and METs (P = 0.037).

Conclusion:

STs may act as a physical sign of underlying raised cardiac atherogenic factors. This may indicates an ongoing risk on coronary circulation which may indicate further corrective action, hopefully early enough. The association of ST with obesity and METs represents a Bermuda Triangle that act against the heart.     

Heat Shock Protein-70 Expression in Vitiligo and its Relation to the Disease Activity

Background:Vitiligo is a progressive depigmenting disorder characterized by the loss of functional melanocytes from the epidermis. The etiopathogenesis of vitiligo is still unclear. Heat shock proteins (HSPs) are prime candidates to connect stress to the skin. HSPs were found to be implicated in autoimmune diseases such as rheumatoid arthritis and other skin disorders as psoriasis.Results:Our analysis revealed a significantly higher expression of HSP-70 mRNA in lesional skin biopsies from vitiligo patients compared to nonlesional skin biopsies from vitiligo patients (P < 0.001) and compared to skin biopsies from healthy controls (P < 0.001). The level of HSP-70 was not found to be correlated with age, sex, or disease duration. The expression of HSP-70 was correlated with the disease activity and patients with active vitiligo showed higher mean HSP-70 level compared to those with inactive disease.Conclusions:HSP-70 plays a role in the pathogenesis of vitiligo and may enhance the immune response in active disease.     

CARDIAC INVOLVEMENT IN PATIENTS OF SYSTEMIC SCLEROSIS

Background:

Systemic sclerosis is a multi-systemic autoimmune disorder. Cardiac involvement by the disease, although not included in the diagnostic criteria, may be seen either clinically, histologically or may be revealed by various investigative modalities.

Purpose:

To see the profile of cardiac involvement in patients of systemic sclerosis.

Materials and Methods:

Forty-seven patients of systemic sclerosis were included in the study. After taking a complete history and doing a detailed physical examination, the patients were submitted to electrocardiogram ECG (all leads), echocardiography and x-ray chest. Furst''s organ indices scoring system for cardiac involvement was followed.

Findings:

Forty-seven patients of systemic sclerosis were included in the study. Five females gave a history of palpitations. A loud pulmonic heart sound was heard in 1. Arrhythmias were observed in 5 patients. Significantly, echocardiography revealed valvular involvement in 5 patients. Left ventricular hypertrophy was seen in 2 patients.

Conclusions:

In our patients, cardiac involvement was rare. In contrast to other studies, valvular involvement was a prominent feature.

Limitations:

Complete evaluation for arrhythmias with 24-h Holter monitor was not used