Thalidomide-Revisited: Are COVID-19 Patients Going to Be the Latest Victims of Yet Another Theoretical Drug-Repurposing?

The coronavirus disease 2019 (COVID-19) pandemic is a worldwide threatening health issue. The progression of this viral infection occurs in the airways of the lungs with an exaggerated inflammatory response referred to as the "cytokine storm" that can lead to lethal lung injuries. In the absence of an effective anti-viral molecule and until the formulation of a successful vaccine, anti-inflammatory drugs might offer a complementary tool for controlling the associated complications of COVID-19 and thus decreasing the subsequent fatalities. Drug repurposing for several molecules has emerged as a rapid temporary solution for COVID-19. Among these drugs is Thalidomide; a historically emblematic controversial molecule that harbors an FDA approval for treating erythema nodosum leprosum (ENL) and multiple myeloma (MM). Based on just one-case report that presented positive outcomes in a patient treated amongst others with Thalidomide, two clinical trials on the efficacy and safety of Thalidomide in treating severe respiratory complications in COVID-19 patients were registered. Yet, the absence of substantial evidence on Thalidomide usage in that context along with the discontinued studies on the efficiency of this drug in similar pulmonary diseases, might cause a significant obstacle for carrying out further clinical evaluations. Herein, we will discuss the theoretical effectiveness of Thalidomide in attenuating inflammatory complications that are encountered in COVID-19 patients while pinpointing the lack of the needed evidences to move forward with this drug.

Turmeric: A condiment, cosmetic and cure.

Turmeric (Curcuma longa L.) is an integral part of Asian culture and cuisine. It has been used in traditional medicine since centuries. A myriad of health benefits have been attributed to it. Curcumin, the most biologically active curcuminoid in turmeric, is being investigated in pre-clinical and clinical trials for its role in disease prevention and cure. It has antioxidant, anti-inflammatory, antineoplastic, anti-proliferative and antimicrobial effects. We review the chemistry of this plant, its cultural relevance in Indian skin care, and its uses in dermatology.

Etanercept in erythema nodosum leprosum.

One of the biggest challenges in treating leprosy is the control of reaction events. Patients with lepromatous leprosy may present reaction type II, or erythema nodosum leprosum, during treatment, and this reaction can remain in a recurrent form after being released from the hospital, requiring the use of thalidomide and/or prednisone for long periods of time, in turn increasing the risk of side effects. Two reports of the use of antiTNF to treat erythema nodosum leprosum were found in the literature. A good response was found after an assay with infliximab and etanercept. This study reports on a patient with lepromatous leprosy and recurrent reaction, controlled by using etanercept and a 10-month follow-up, with the interruption of thalidomide and the maintenance of prednisone at 10 mg/day.

Etanercept in erythema nodosum leprosum

Abstract: One of the biggest challenges in treating leprosy is the control of reaction events. Patients with lepromatous leprosy may present reaction type II, or erythema nodosum leprosum, during treatment, and this reaction can remain in a recurrent form after being released from the hospital, requiring the use of thalidomide and/or prednisone for long periods of time, in turn increasing the risk of side effects. Two reports of the use of antiTNF to treat erythema nodosum leprosum were found in the literature. A good response was found after an assay with infliximab and etanercept. This study reports on a patient with lepromatous leprosy and recurrent reaction, controlled by using etanercept and a 10-month follow-up, with the interruption of thalidomide and the maintenance of prednisone at 10 mg/day.

Effects of over-the-counter sales restriction of antibiotics on substitution with medicines for symptoms relief of cold in Mexico and Brazil: time series analysis.

We evaluated changes in the use of non-steroidal anti-inflammatory drugs (NSAIDs), non-opioid analgesics and cough and cold medicines and its relation with the use of antibiotics after the over-the-counter (OTC) antibiotic sales restrictions in Mexico and Brazil. IMS Health provided retail quarterly data from the private sectors in Mexico and Brazil from the first quarter of 2007 to the first quarter of 2013. Data of each active substance of antibiotics, easily accessible medicines perceived as antibiotics substitutes (cough and cold medicines, analgesics and NSAIDs-the latter two being combined in the analyses), and medicines to control for external factors that can affect the medicines usage trend (antihypertensives) were converted from kilograms to defined daily doses per 1000 inhabitants days (DDD/TID). Interrupted time series were used to estimate changes in level of medicines use at the intervention point and slope after the regulation. The Gregory-Hansen cointegration test was used to explore the relation between the use of antibiotics and perceived substitutes. After the regulation in Mexico NSAIDs-analgesics usage level increased by 1.1 DDD/TID with a slope increase of 0.2 DDD/TID per quarter and the cough and cold medicines usage level increased by 0.4 DDD/TID. In Brazil NSAIDs-analgesics usage level increased by 1.9 DDD/TID, and cough and cold medicines did not change. In the two countries, NSAIDs-analgesics usage changes were related with antibiotic usage changes; in Mexico cough and cold medicines usage changes had a relation with the antibiotics usage changes. These results showed a substitution effect on the use of other medicines, especially NSAIDs and analgesics, after reinforcement of OTC antibiotics sales restrictions. These regulations aimed to improve the antibiotics use and as a consequence reduce antimicrobial resistance; however, this type of policies should be comprehensive and take into account the potential substitution effects on the use of other medicines.

Systemic lupus erythematosus: review of synthetic drugs.

INTRODUCTION: Synthetic drugs are prescribed for nearly all patients with systemic lupus erythematosus (SLE), a multisystem autoimmune disease, to ameliorate symptoms and positively influence outcome. While only 2 biologic agents have been approved for the treatment of SLE, synthetic drugs are still the mainstay of therapy in SLE. The highly variable and unpredictable course of SLE poses a challenge for physicians as to what drug(s) should be prescribed for which patient. AREAS COVERED: Previous and recent studies have evaluated several synthetic drugs in the treatment of SLE. This article reviews currently available evidence for the efficacy and safety of synthetic drugs in SLE and discusses future treatment perspectives. EXPERT OPINION: Hydroxychloroquine should be considered an anchor drug in SLE because of the multiple beneficial effects of this agent. When patients present with persistent disease activity despite hydroxychloroquine therapy or need higher dosages and/or prolonged use of glucocorticoids (GCs), additional immunosuppressants should be promptly prescribed. Based on available evidence, azathioprine and mycophenolate mofetil are the drugs of first choice. Determination of a 'safe' GC dose for chronic daily use is of major importance and should be subject of further studies in large patient populations.

Profile of oxidative stress in response to treatment for type 1 leprosy reaction.

OBJECTIVE: To measure oxidative stress in Type 1 leprosy reaction, and to document the effect of anti-leprosy multidrug therapy (MDT) and anti-reaction drugs on measures of oxidative stress. MATERIALS AND METHODS: A prospective study was carried out at a teaching hospital involving consecutive patients with Type 1 reaction. MDA (malondialdehyde), FRAP (ferric reducing ability of plasma) and GSH (reduced glutathione) were measured in venous blood samples as measures of oxidative stress and compared at inclusion, after 4 weeks of initial therapy (following standard guidelines including MDT, NSAIDS, and systemic steroids), and 4 weeks after clinical remission. RESULTS: The final study cohort included 40 patients with Type 1 reaction (different treatment arms) after excluding for confounding factors such as prior treatment, smoking, NSAID use or concurrent illness requiring therapy. Measures of lipid derived oxidative stress assessed by MDA showed a significant rise with 4 weeks of therapy and a trend towards decline after clinical resolution. In contrast, the other two measures of anti-oxidants namely GSH and FRAP, showed a significant decrease (P < 0.05) at 4 weeks of treatment followed by a significant increase after 4 weeks of clinical remission of reaction. CONCLUSION: MDT and anti-reactional treatment is associated with significant increases in FRAP and GSH levels, reflecting a reduction in the oxidative stress in patients treated for Type 1 reaction. However, lipid peroxidation as measured by MDA is only partially controlled with treatment.

Spontaneous regression of lumbar Hansen type 1 disk extrusion detected with magnetic resonance imaging in a dog.

CASE DESCRIPTION: A 3-year-old French Bulldog was evaluated because of acute signs of back pain and spastic paraparesis. CLINICAL FINDINGS: Neuroanatomic localization indicated a lesion in the T3-L3 spinal cord segment. Magnetic resonance imaging revealed extradural spinal cord compression at the ventral right aspect of the intervertebral disk space L3-4. On the basis of these findings, a diagnosis of sequestrated Hansen type 1 disk extrusion without extradural hemorrhage was made. TREATMENT AND OUTCOME: The dog was treated conservatively with cage rest, restricted exercise on a leash, and NSAIDs. Results of follow-up examination 5 weeks later indicated complete resolution of clinical signs, and results of repeated MRI indicated a 69% reduction in the volume of the herniated disk material. CLINICAL RELEVANCE: Findings for the dog of this report indicated spinal cord compression attributable to extruded intervertebral disk material resolved. Functional improvements in dogs with such problems may be partly attributable to spontaneous regression of intervertebral disk extrusions.

Diagnosis and management of psoriatic arthritis.

Psoriatic arthritis (PsA) is a multi-faceted disease marked by varying combinations of peripheral arthritis, dactylitis, spondylitis, and enthesitis. Rarely, recurrent uveitis occurs. Skin involvement may or may not exist. However, patients with nail psoriasis have a higher probability of developing PsA. Untreated patients have significant morbidity and mortality. Timely diagnosis and aggressive treatment of the disease can lead to lower morbidity. Drug therapy of PsA includes symptomatic therapy and therapy with disease-modifying anti-rheumatic drugs. Biologics are the only agents that address all the pathological changes, of this chronic condition.

Is there a relation between hemicrania continua and leprosy?

The association of hemicrania continua and leprosy has been described in 2008. This relation can be causal or casual. Hemicrania continua is a strictly unilateral, moderate to severe, continuous, indomethacin-responsive primary headache with autonomic cranial symptoms and leprosy is an usual cause of peripheral neuropathy. Prevalence has fallen in the past years, but transmission continues and leprosy remains a public health problem. The objective of this study is to report one case of headache fulfilling the IHS criteria for HC, presented during the course of leprosy. A 61 years old woman started hypo and hiperpigmented lesions with impaired sensation to touch on right side of face (malar). She had biopsy in facial lesion and histopathology compatible with a borderline leprosy form. At the same time, she reported new headaches, daily and continuous, without pain-free periods, unilateral (which were located in the same side of the leprosy lesion in face), throbbing and severe (VAS = 8) with ipsilateral conjuntival injection and lacrimation that improved with indomethacin. We hypothesize that the local injury on the face of this patient predisposes a mechanism of central sensitization, resulting in trigeminal autonomic cephalgia. Relation between trigemino-autonomic cephalalgias and leprosy provides insights into craniofacial pain mechanisms.

Immunization with pVAXhsp65 decreases inflammation and modulates immune response in experimental encephalomyelitis.

BACKGROUND: A DNA vaccine (pVAXhsp65) containing the gene of a heat-shock protein (hsp65) from Mycobacterium leprae showed high immunogenicity and protective efficacy against tuberculosis in BALB/c mice. A possible deleterious effect related to autoimmunity needed to be tested because hsp65 is highly homologous to the correspondent mammalian protein. In this investigation we tested the effect of a previous immunization with DNAhsp65 in the development of experimental autoimmune encephalomyelitis (EAE), a rat model of multiple sclerosis. METHODS: Female Lewis rats were immunized with 3 pVAXhsp65 doses by intramuscular route. Fifteen days after the last DNA dose the animals were evaluated for specific immunity or submitted to induction of EAE. Animals were evaluated daily for weight loss and clinical score, and euthanized during the recovery phase to assess the immune response and inflammatory infiltration at the central nervous system. RESULTS: Immunization with pVAXhsp65 induced a specific immune response characterized by production of IgG(2b) anti-hsp65 antibodies and IFN-gamma secretion. Previous immunization with pVAXhsp65 did not change EAE clinical manifestations (weight and clinical score). However, the vaccine clearly decreased brain and lumbar spinal cord inflammation. In addition, it downmodulated IFN-gamma and IL-10 production by peripheral lymphoid organs. CONCLUSION: Our data demonstrated that this vaccine does not trigger a deleterious effect on EAE development and also points to a potential protective effect.

Use of clofazimine in dermatology.

Clofazimine is the riminophenazine dye that, due to its antibacterial and anti-inflammatory properties, has been used for several diseases. This article reviews all major characteristics and uses relating to clofazimine, from its pharmacology to its indications in several skin diseases, over and above its classical and well established use in the treatment of leprosy. Due to its anti-inflammatory and antimicrobial properties, clofazimine has a wide spectrum for application in dermatology. The indications include neutrophilic, granulomatous and infectious diseases. Although it is not the first-choice medication in most of the cases, clofazimine should always be considered among the therapeutic options in refractory cases.

Anti-inflammatory activity of superoxide dismutase obtained from Debaryomyces hansenii on type II collagen induced arthritis in rats.

INTRODUCTION: Rheumatoid arthritis is an autoimmune inflammatory disease of unknown etiology, free radicals have been implicated in the genesis and perpetuation of damage in this pathology. OBJECTIVE: To evaluate the anti-inflammatory effect of Cu,Zn-superoxide dismutase (SOD) obtained from two different sources (bovine erythrocytes, Be-SOD, and Debaryomyces hansenii, Dh-SOD) with Type II Collagen-induced Arthritis model in rats. MATERIAL AND METHODS: Arthritis was induced by repeated injection of a porcine type II collagen-incomplete Freund adjuvant suspension on the back of Dark Augui (DA) rats. Arthritis was clinically evaluated throughout the study. Body weight was determined at three different times. Two different doses for each treatment (Be-SOD, Dh-SOD) were tested: 100 and 1,000 U/kg. At the end of the trial (day 28), histological analyses of the most inflamed ankle joint, as well as serum anti-collagen antibodies, were determined. RESULTS: Both sources of SOD decreased, although to a different extent, the incidence and severity of the disease. Arthritis score was lower in all treatments, except for the low dose of Be-SOD. Groups receiving either source of SOD showed a significant weight increase compared to the placebo group. Histological damage was similar in all groups. Only the group that received the highest dose of Dh-SOD showed a significant lower antibody titer; nevertheless, no correlation appears to derive from arthritis score and antibody titer. CONCLUSION: Our findings suggest that, although unable to counteract the arthritis syndrome, SOD may still be beneficial due to its anti-inflammatory activity. In the case of Dh-SOD, the best effect was observed at the highest dose tested.

Pentoxifylline: a drug with wide spectrum applications in dermatology.

Pentoxifylline (PTX) is a methylxanthine derivative with a variety of anti-inflammatory effects. Currently, PTX is approved by the Food and Drug Administration for the treatment of intermittent claudication, but studies have shown that it has a variety of physiological effects at the cellular level, which may be important in treating a diverse group of diseases.