Molecular and epidemiological characterization of recurrent Mycobacterium ulcerans infections in Benin

Background Buruli ulcer is a neglected tropical disease caused by Mycobacterium ulcerans, an environmental mycobacterium. Although transmission of M. ulcerans remains poorly understood, the main identified risk factor for acquiring Buruli ulcer is living in proximity of potentially contaminated water sources. Knowledge about the clinical features of Buruli ulcer and its physiopathology is increasing, but little is known about recurrence due to reinfection. Methodology/Principal findings We describe two patients with Buruli ulcer recurrence due to reinfection with M. ulcerans, as demonstrated by comparisons of DNA from the strains isolated at the time of the first diagnosis and at recurrence. Based on the spatial distribution of M. ulcerans genotypes in this region and a detailed study of the behavior of these two patients with respect to sources of water as well as water bodies and streams, we formulated hypotheses concerning the sites at which they may have been contaminated. Conclusions/Significance Second episodes of Buruli ulcer may occur through reinfection, relapse or a paradoxical reaction. We formally demonstrated that the recurrence in these two patients was due to reinfection. Based on the sites at which the patients reported engaging in activities relating to water, we were able to identify possible sites of contamination. Our findings indicate that the non-random distribution of M. ulcerans genotypes in this region may provide useful information about activities at risk.

Homeopathic use of modern drugs: therapeutic application of the organism paradoxical reaction or rebound effect

When Samuel Hahnemann systematized homeopathy and the effects of drugs on the state of human health, he described the primary action of drugs and the following secondary and opposite reaction of the organism. Seeking to apply this secondary action or vital reaction of the organism as therapeutic method, he postulated the principle of similitude, i.e. the prescription to ill individuals of drugs that cause similar symptoms in the healthy (similia similibus curentur). In modern pharmacology, secondary action (vital reaction) of drugs is known as rebound effect or paradoxical reaction of the organism. It has been observed after discontinuation of several classes of palliative (enantiopathic) drugs, namely those that act according to the principle of contraries (contraria contrariis curentur). Although in this case it is associated with severe and fatal iatrogenic events, rebound effect might awaken a healing reaction when the very same drug is employed according to the principle of similitude. The validity of the principle of similitude is proved by scientific evidence on rebound effect, whereas conventional drugs primary (therapeutic, adverse and side) effects might be equated to pathogenetic manifestations and thus be homeopathically applied. For this purpose a homeopathic materia medica and repertory comprising 1,251 modern drugs was elaborated using the monographs described in The United States Pharmacopeia Dispensing Information as source (www.newhomeopathicmedicines.com). Thus, the therapeutic range of homeopathy is broadened through the addition of hundreds of new medicines that might be employed in every kind of disease including countless modern clinical syndromes.

Medication-Related Osteonecrosis of the Jaw: A Critical Narrative Review

Background: Nearly two decades have passed since a paradoxical reaction in the orofacial region to some bone modifying agents and other drugs was recognized, namely medication-related osteonecrosis of the jaw (MRONJ). Purpose: The aim of this manuscript was to critically review published data on MRONJ to provide an update on key terminology, concepts, and current trends in terms of prevention and diagnosis. In addition, our objective was to examine and evaluate the therapeutic options available for MRONJ. Methods: The authors perused the most relevant literature relating to MRONJ through a search in textbooks and published articles included in several databases for the years 2003–2021. Results and conclusions: A comprehensive update of the current understanding of these matters was elaborated, addressing these topics and identifying relevant gaps of knowledge. This review describes our updated view of the previous thematic blocks, highlights our current clinical directions, and emphasizes controversial aspects and barriers that may lead to extending the accumulating body of evidence related to this severe treatment sequela.

Potential disease trigger as a therapeutic option: infliximab for paradoxical reaction in tuberculosis of the central nervous system

A 36-year-old man of central Asian origin was diagnosed with subacute disseminated tuberculosis. Initially, central nervous system involvement was suggested by an encephalopathic condition and MRI showing extensive basal and spinal meningitis. After initiation of anti-tuberculosis drugs and corticosteroid therapy, clinical and radiological deterioration of spinal damage was noted. We interpreted this in the context of a paradoxical reaction, which is suggested to be an overshooting inflammatory response after reconstitution of the immune system. Despite increased dosage of corticosteroids, a gradual worsening of gait ataxia over several weeks was noted. After administration of infliximab, the patient’s condition progressively improved.

Atopic Dermatitis as a Paradoxical Effect of Secukinumab for the Treatment of Psoriasis

In the therapeutic arsenal to treat moderate to severe psoriasis, the new agents are secukinumab and ustekinumab, which are fully human monoclonal antibodies, directed against IL-17A and IL-12/23, respectively, which have been shown to be effective and safe in several studies. Their side effects are rare, and the most frequently reported side effects were infection, especially nasopharyngitis, headache, pruritus, high blood pressure, and low back pain. Unlike the side effects, the paradoxical reaction can be defined by the appearance or exacerbation of a pathological condition that usually responds to a certain class of drug. The appearance of this reaction in patients using anti-interleukins is poorly described; however, as they are new drugs, they may be more common than the literature reports. We describe a case of a paradoxical reaction, with the appearance of atopic dermatitis, after using secukinumab to treat psoriasis.