Biologics in Dermatology: An Integrated Review

The advent of biologics in dermatologic treatment armentarium has added refreshing dimensions, for it is a major breakthrough. Several agents are now available for use. It is therefore imperative to succinctly comprehend their pharmacokinetics for their apt use. A concerted endeavor has been made to delve on this subject. The major groups of biologics have been covered and include: Drugs acting against TNF-α, Alefacept, Ustekinumab, Rituximab, IVIG and Omalizumab. The relevant pharmacokinetic characteristics have been detailed. Their respective label (approved) and off-label (unapproved) indications have been defined, highlighting their dosage protocol, availability and mode of administration. The evidence level of each indication has also been discussed to apprise the clinician of their current and prospective uses. Individual anti-TNF drugs are not identical in their actions and often one is superior to the other in a particular disease. Hence, the section on anti-TNF agents mentions the literature on each drug separately, and not as a group. The limitations for their use have also been clearly brought out.     

Neonatal Purpura Fulminans Due to Methicillin Resistant Staphylococcus aureus

Abstract: Neonatal purpura fulminans is rare and may be inherited or acquired. It may ultimately lead to multiorgan failure and death. Purpura fulminans in a premature neonate resulting from Staphylococcus aureus septicemia is illustrated. Unfortunately, the baby succumbed to septicemia.     

Evaluation of analgesic efficacy,gastrotoxicity and nephrotoxicity of fixed-dose combinations of nonselective,preferential and selective cyclooxgenase inhibitors with paracetamol in rats

Nonsteroidal anti-inflammatory drugs (NSAIDs) are combined with paracetamol (PCM) with a view to enhance analgesic efficacy and reduce gastric toxicity. However, there are reports of enhanced nephrotoxicity with nonselective NSAID with PCM combinations. The present study investigated the analgesic efficacy, gastrotoxicity and nephrotoxicity of nonselective, preferential and selective cyclooxgenase inhibitors and their combination with PCM in rats.Graded doses of ibuprofen, meloxicam and celecoxib alone and their combination with fixed dose of PCM were administered to the rats by gavage for 14 days. The results showed that PCM potentiated the analgesic effect of all three classes of NSAIDs significantly as evidenced by increase in tail-flick latency in radiant heat method. Dose-dependent gastromucosal damage was produced by all the drugs, which was augmented significantly with PCM in the form of decreased total carbohydrate/protein ratio of mucin and increased gastric ulcer index. It was further confirmed by histopathology of rat’s stomach. The renal histopathology was conducted to evaluate inflammation, tubular damage, papillary necrosis, and interstitial changes. Increased nephrotoxicity was observed with all NSAIDs in dose-dependent manner and in combination with PCM.Our study revealed the augmented analgesia as well as enhanced gastrotoxicity and nephrotoxicity with all three major NSAIDs classes when combined with PCM. These findings highlighted the need for large pharmacoepidemiological studies to evaluate the magnitude of gastrotoxicity and nephrotoxicity in population who are on long-term treatment with NSAID combinations.     

Sexually transmitted diseases in children

Sexually transmitted diseases (STDs) cause considerable morbidity among their victims. This is true even for children. Unfortunately, this aspect has not received due attention and remains a relatively ignored field. We carried out a study of the clinico-epidemiological profile of STDs among the pediatric patients who attended the STD clinic of a tertiary care hospital. Pediatric patients who presented with STDs from January of 1995 to February of 2001 constituted the subject material of this study. A detailed clinical examination and relevant laboratory investigations were carried out in all patients. A total of 15,453 STD patients were seen during this period, out of which 127 were children, giving a prevalence of 0.82% pediatric STD cases. The peak incidence of STDs was seen in the age group of 10-14 years (66.1%). Most of them were illiterate (61.4%) and from low socio-economic backgrounds (70.9%). Notably, 17.3% were from remand homes. The predominant STDs observed among these children were syphilis (25.2%), including six cases of congenital syphilis, vulvo-vaginal candidiasis (11.8%), condyloma-acuminata (14.2%), herpes progenitalis (8.7%) and traumatic lesions (7.9%). Histories or signs of abuse were present in 74% of the patients. Only two cases during the span of the study were HIV positive. Pediatric STDs remain a hidden and neglected problem. Children constituted 0.82% of all STD patients in our series. This may represent only the tip of the iceberg, because several features, including some operational problems, are responsible for underdiagnosis of pediatric STDs. If not treated promptly and adequately, they may result in significant physical and emotional sequelae in children. Thus, it is essential to develop strategies to prevent sexual abuse and to have adequate counselling measures, especially in juvenile delinquents.     

Topical prostaglandin analog (PGE2) in vitiligo--a preliminary study

BACKGROUND: Several therapeutic options are available for the treatment of vitiligo, but none is uniformly effective. Prostaglandin has been shown to play a role in melanocyte proliferation and melanogenesis. Topical application of prostaglandin E2 (PGE2) over mice skin has been shown to increase melanocyte density. AIM: To evaluate the role of topical PGE2 in the treatment of vitiligo. METHODS: We enrolled 27 patients with limited vitiligo lesions in this study. Patients were instructed to apply a translucent gel containing 0.5 mg/3 g (166.6 micro g/g) PGE2 to depigmented skin. RESULTS: Twenty-four patients were evaluated at the end of 6 months, as three patients withdrew for reasons unrelated to the study. At the end of treatment, 15 patients showed marked to complete repigmentation and three patients showed moderate repigmentation. The remaining six patients showed none to minimal repigmentation. CONCLUSIONS: Marginal repigmentation with hyperpigmented borders was seen in the majority of lesions. Our results are encouraging and offer a new and potentially efficacious treatment for this pigmentation disorder.     

Cervicofacial nocardiosis in an immunocompetent child

Nocardiosis occurs primarily as an opportunistic infection in an immunocompromised host. The infection may on rare occasion occur in a normal host confounding the diagnosis. It is also notably an uncommon infection in children. We report a 1-y-old girl with cervicofacial nocardial infection who presented with acute suppurative otitis media and lymphadenitis. This child did not have any predisposing risk factors for this infection and responded well to treatment with co-trimoxazole and chloramphenicol. She is doing well on follow-up. CONCLUSION: Nocardiosis in an immunocompetent small child is reported.     

Tuberculosis verrucosa cutis: antitubercular therapy, a well-conceived diagnostic criterion

A 39-year-old housewife sustained inadvertent trauma to the right index finger about 6 years ago, whilst stitching clothes. A couple of weeks later, the site of trauma became hard and gritty. Ever since, it has progressed slowly, without any appreciable outward sign. It was not associated with any discomfort/pain. Consequent on an opinion from a surgeon, it was decided to operate on the right index finger. During the operation, under local anesthesia, a hard and gritty material was removed. The material was subjected to histopathologic study. Several stitches were applied to the wound. It failed to respond to antimicrobial therapy over a 4-week period, prompting the patient to seek another opinion. Examination of the skin surface revealed a plaque with an irregular configuration on and around the distal interphalangeal joint of the right index finger. It was erythematous and pigmented. The top of the plaque was irregular and had alternating elevations and depressions ( Fig. 1 ). Diascopy was negative for apple jelly nodule. A bacillus Calmette–Guérin (BCG) vaccination scar was identified on the left deltoid. There was no regional lymphadenopathy or systemic abnormality. Mantoux test with intradermal injection of 0.1 mL SPAN's tuberculin (purified protein derivative/5 tuberculin units/0.1 mL) (Span Diagnostic Ltd., Murat, India) was negative after 72 h. Investigations, including total and differential leukocyte count, erythrocyte sedimentation rate, serum biochemistry, and renal and liver function tests, were within the normal range, as was a chest X-ray.

Figure 1 Open in figure viewer PowerPoint Tuberculosis verrucosa cutis before (a) and after (b) antitubercular therapy (ATT)     

Multifocal scrofuloderma with disseminated tuberculosis in a severely malnourished child

Tuberculosis and malnutrition continue to be significant health problems in developing countries. Moderate to severe malnutrition can cause immunosuppression and predispose children to various infections. We report disseminated tuberculosis in a severely malnourished Indian child who presented primarily with cutaneous involvement.