Research Articles (Dermatology)

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Molecular epidemiology of multidrug-resistant Klebsiella pneumoniae, Enterobacter cloacae, and Escherichia coli outbreak among neonates in Tembisa hospital, South Africa
(Frontiers Media, 2024-02) Osei Sekyere, John; Mmatli, Masego; Bosch, Anel; Ntsoane, Ramathetje V.; Naidoo, Harishia; Doyisa, Sinenhlanhla; Maningi, Nontuthuko Excellent; Mbelle, Nontombi Marylucy; Said, Mohamed; j.oseisekyere@up.ac.za
BACKGROUND: An outbreak of multidrug-resistant Klebsiella pneumoniae, Escherichia coli, and Enterobacter cloacae infections in a neonatal ward within a tertiary hospital in South Africa resulted in the mortality of 10 patients within six months. In this work, the genomic epidemiology of and the molecular factors mediating this outbreak were investigated. METHODS: Bacterial cultures obtained from clinical samples collected from the infected neonates underwent phenotypic and molecular analyses to determine their species, sensitivity to antibiotics, production of carbapenemases, complete resistance genes profile, clonality, epidemiology, and evolutionary relationships. Mobile genetic elements flanking the resistance genes and facilitating their spread were also characterized. RESULTS: The outbreak was centered in two major wards and affected mainly neonates between September 2019 and March 2020. Most isolates (n = 27 isolates) were K. pneumoniae while both E. coli and E. cloacae had three isolates each. Notably, 33/34 isolates were multidrug resistant (MDR), with 30 being resistant to at least four drug classes. All the isolates were carbapenemasepositive, but four blaOXA-48 isolates were susceptible to carbapenems. BlaNDM-1 (n = 13) and blaOXA-48/181 (n = 15) were respectively found on IS91 and IS6-like IS26 composite transposons in the isolates alongside several other resistance genes. The repertoire of resistance and virulence genes, insertion sequences, and plasmid replicon types in the strains explains their virulence, resistance, and quick dissemination among the neonates. CONCLUSIONS: The outbreak of fatal MDR infections in the neonatal wards were mediated by clonal (vertical) and horizontal (plasmid-mediated) spread of resistant and virulent strains (and genes) that have been also circulating locally and globally.
Editorial : Molecular mechanisms of resistance to “last resort” antimicrobials in Enterobacterales
(Frontiers Media, 2024-05) Osei Sekyere, John; Schneiders, Thamarai; Majewski, Piotr; j.oseisekyere@up.ac.za
No abstract available.
Molecular characterization of hypermucoviscous carbapenemase-encoding Klebsiella pneumoniae isolates from an Egyptian hospital
(Wiley, 2024-05) Ragheb, Suzan Mohammed; Osei Sekyere, John; j.oseisekyere@up.ac.za
This study aimed to screen antibiotic resistance and virulence genes in carbapenemresistant hypermucoviscous Klebsiella pneumoniae isolates from an Egyptian hospital. Among 38 previously confirmed carbapenem-nonsusceptible K. pneumoniae isolates, a string test identified three isolates as positive for hypermucoviscosity. Phenotypic characterization and molecular detection of carbapenemase- and virulence-encoding genes were performed. PCR-based multilocus sequence typing and phylogenetics were used to determine the clonality and global epidemiology of the strains. The coexistence of virulence and resistance genes in the isolates was analyzed statistically using a chisquare test. Three isolates showed the presence of carbapenemase-encoding genes (blaNDM, blaVIM, and blaIMP), adhesion genes (fim-H-1 and mrkD), and siderophore genes (entB); the isolates belonged to sequence types (STs) 101, 1310, and 1626. The relatedness between these sequence types and the sequence types of globally detected hypermucoviscous K. pneumoniae that also harbor carbapenemases was determined. Our analysis showed that the resistance and virulence profiles were not homogenous. Phylogenetically, different clones clustered together. There was no significant association between the presence of resistance and virulence genes in the isolates. There is a need for periodic surveillance of the healthcare settings in Egypt and globally to understand the true epidemiology of carbapenem-resistant, hypermucoviscous K. pneumoniae.
The SARS-COV-2 seroprevalence among oncology patients
(MDPI, 2023-01-09) Kgatle, Mankgopo; Das, Rajesh; Lawal, Ismaheel Opeyemi; Boshomane, Tebatso M.G.; Mokoala, Kgomotso M.G.; Gaspar, Cattleya; Mbokazi, Lydia; Nkambule, Nonhlanhla; Gow, Veronique; Ndlovu, Honest; Mzizi, Yonwaba; Chalwe, Joseph; Diphofa, Jeaneth; Mokobodi, Dinah; Gxekwa, Nobuhle; Zongo, Lusanda; Maphosa, Tinashe; Vorster, Mariza; Bassa, Sheynaz; Venkatesan, Amouda; Khanyile, Richard; Munga, Yunus; Ebenhan, Thomas; Zeevaart, Jan Rijn; Sathekge, Mike Machaba; mike.sathekge@up.ac.za
Patients with cancer are presumed to be vulnerable to an increased risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severe clinical outcomes due to the immunocompromised state mediated by their underlying malignancies and therapy. The aim of this study was to estimate the SARS-CoV-2 seroprevalence, following second to fourth waves in solid tumour patients attending the Steve Biko Academic Hospital (SBAH) for diagnosis and treatment of cancer. We used the single-prick COVID-19 IgG/IgM Rapid Test Cassettes to detect SARS-CoV-2 IgG/IgM antibodies in 760 patients with solid tumours who were asymptomatic and who had never tested positive for coronavirus disease 2019 (COVID-19). Out of the 760 patients, 277 were male (36.4%), 483 were female (63.6%), and the mean age was 55 years (range 18–92). The estimated total seroprevalence was 33.2%. The seroprevalence status of the COVID-19 IgG/IgM antibodies rose significantly from the second wave (11.3%) to the third (67.38%) and then the fourth (69.81%) waves with roughly similar counts. A significant number of the seropositive patients were asymptomatic to COVID-19 (96%). There was a higher rate of seropositivity in cancer patients with hypertension (p < 0.05). Patients with breast, gynaecologic, and prostate cancers exhibited increased SARS-CoV-2 seropositivity. Although oncology patients may be susceptible to SARS-CoV-2 infection, our data indicate that these patients remained asymptomatic throughout various waves with an overall COVID-19 IgG/IgM antibody seropositivity of 33.16%, suggesting no risk of severe or fatal cases of COVID-19.
Editorial : Community series - characterization of mobile genetic elements associated with acquired resistance mechanisms, volume II
(Frontiers Media, 2023-06-22) Osei Sekyere, John; Kerdsin, Anusak; Chopjitt, Peechanika; Wendling, Carolin Charlotte
Antibiotic resistance in bacteria remains a great challenge to clinical medicine as resistant bacterial infections are very difficult to manage. It is estimated that antibiotic-resistant infections resulted in 1.27 million deaths in 2019, which is expected to increase to 10 million deaths annually by 2050 (Antimicrobial Resistance Collaborators, 2022). In the US alone, at least 2 million people got an antimicrobial-resistant infection, of which at least 23,000 people died in 2019 (CDC, 2019). In the EU, 541,000 deaths were associated with antibiotic resistance while 133,000 deaths were attributable to this menace (European Antimicrobial Resistance Collaborators, 2022). Moreover, the costs associated with antibiotic resistance have been estimated by Nelson et al. (2022) to be $1.9 billion in just a retrospective study. In another study conducted by the CDC and the University of Utah School of Medicine, it was concluded that $4.6 billion in health care costs accrued annually from treating antibiotic resistance in six pathogens in the US (CDC, 2021). These statistics evince why the WHO has categorized antibiotic resistance among the top 10 threats for global health (Antimicrobial Resistance Collaborators, 2022).
Biomarkers for disease progression identified in psoriasis patients : a pilot study
(Wiley, 2023-09) Mkhize, Nomzamo; Kgokolo, Mahlatse C.M.; Steel, Helen C.; Meyer, Pieter Willem Adriaan; Kwofie, Luyanda Laura Illicia; luyanda.kwofie@up.ac.za
BACKGROUND : Psoriasis is an immune-mediated polygenic skin disorder. It is influenced by multiple genes as well as environmental factors including infection and trauma. Psoriasis is associated with molecular biomarkers such as HLA-C*06:02 and associated single-nucleotide variants (SNVs). Furthermore, the circulatory cytokines, interleukin (IL)-17 and IL-23 are elevated in psoriasis patients. OBJECTIVES : To investigate the incidence of biomarkers namely, HLA-C*06:02, SNV's (rs30187, rs27044, rs2248374), and IL17 and IL23 as possible diagnostic/prognostic biomarkers of value, individually or in combination in psoriasis patients. METHODS : These biomarkers, HLA-C*06:02, SNV's (rs3018, rs27044, rs2248374), and IL17 and IL23 (and their ratio) were tested in a cohort of 40 psoriasis patients attending a dermatology clinic situated in a tertiary academic hospital as well as 40 healthy controls by: HLA typing using sequence-specific primers (PCR SSP), real time PCR, and Luminex technology, respectively. RESULTS : HLA-C*06:02 was significantly elevated in our patient cohort with 53% (n = 21) of psoriasis patients expressing the HLA-C*06:02 allele versus 15% (n = 6), p = 0.001 in the healthy controls. Both IL-17 and IL-23 were significantly elevated in the psoriasis patients compared to the normal controls (p = 0.0001 and p = 0.0005, respectively). The SNV rs2248374 showed an association with both IL-17 and HLA-C*06:02 in patients with psoriasis. CONCLUSIONS : Overall, these novel findings are the first to be published for South African and African populations in the public health sector. The finding of the current study corroborates international studies. Further validation through geographic and population expansion may assist in identifying individuals at risk of disease progression in psoriasis. These biomarkers may be used as potential prognosticators which will offer the opportunity for early medical intervention to reduce the burden of disease.
Reticular erythematous mucinosis in an African woman with HIV infection : case report and literature review
(Karger, 2023) Tenea, Daniela; Campaini, Cinzia
Reticular erythematous mucinosis is a rare and persistent form of primary idiopathic mucinosis, often referred to as plaque-like cutaneous mucinosis or midline mucinosis. It presents with reticulate patches or erythematous plaques with predilection for the anterior and posterior trunk. Affected patients are frequently asymptomatic. Pruritus or burning sensations were reported after exposure to the sun. The aetiology remains obscure; its pathogenesis is poorly understood, particularly in immunocompromised patients such as HIV-infected patients. The disease associations are not uniformly documented. Antimalarial agents significantly improve and shorten the course of the disease. We report a case of a 31-year-old African woman with underlying HIV infection who displayed the classical clinical and histological features of reticular erythematous mucinosis. This condition is rare among the HIV-infected patients, particularly in those of African descent, in whom lichen myxoedematosus/scleromyxoedema variants and acral persistent papular mucinoses were most frequently reported. The higher incidence of photosensitivity in HIV-infected individuals including the patients with skin of colour may play a potential role in reticular erythematous mucinosis. Its relationship with lupus erythematosus and photosensitivity in the context of HIV infection is discussed. To the best of our knowledge, this is the first reported case of reticular erythematous mucinosis in an African HIV-infected patient. This case highlights the need for diagnostic awareness in cases presenting with erythematous plaques and patches in a net-like pattern developing on the midline and sun-exposed areas of the trunk.
Transforming growth factor-β1 and soluble co-inhibitory immune checkpoints as putative drivers of immune suppression in patients with basal cell carcinoma
(Elsevier, 2024-04) Kgokolo, C.M.; Malinga, Nonkululeko Z.; Steel, Helen C.; Meyer, Pieter Willem Adriaan; Smit, Teresa; Anderson, Ronald; Rapoport, Bernardo Leon; mahlatse.kgokolo@up.ac.za
The current study compared the levels and possible associations between systemic soluble immune checkpoints (sICPs, n = 17) and a group of humoral modulators of immune suppressor cells ( n = 7) in a cohort of patients with basal cell carcinoma (BCC, n = 40) and a group of healthy control subjects ( n = 20). The seven humoral modulators of immunosuppressor cells were represented by the enzymes, arginase 1 and fibroblast activation protein (FAP), the chemokine, RANTES (CCL5) and the cytokines, interleukin-10 and transforming growth factor-β1 (TGF-β1), as well as the M2-type macrophage markers, soluble CD163 (sCD163) and sCD206. The plasma levels of six co-inhibitory sICPs, sCTLA-4, sLAG-3, sPD-1, sPD-L1, sTIM-3 and sPD-L2 were significantly elevated in the cohort of BCC patients ( p <0.001- p <0.00001), while that of sBTLA was significantly decreased ( p <0.006). Of the co-stimulatory sICPs, sCD27 and sGITR were significantly increased ( p< 0.0002 and p< 0.0538) in the cohort of BCC patients, while the others were essentially comparable with those of the control participants; of the dual active sICPs, sHVEM was significantly elevated ( p <0.00001) and TLR2 comparable with the control group. A correlation heat map revealed selective, strong associations of TGF-β1 with seven co-stimulatory ( z = 0.618468–0.768131) and four co-inhibitory ( z = 0.674040–0.808365) sICPs, as well as with sTLR2 ( z = 0.696431). Notwithstanding the association of BCC with selective elevations in the levels of a large group of co-inhibitory sICPs, our novel findings also imply the probable involvement of TGF-β1 in driving immunosuppression in this malignancy, possibly via activation of regulatory T cells. Notab
Merkel cell carcinoma of the head in a young African Albino woman with HIV/HTLV-1 coinfection associated with multiple squamous cell carcinomas
(Karger, 2019) Tenea, Daniela; Dinkel, Jurgen Erich; Becker, Jurgen C.; Van der Walt, Elizabeth
Merkel cell carcinoma (MCC) is a rare cutaneous neoplasm of presumed neuroendocrine origin, with aggressive behavior and poor prognosis, that tends to have an increased incidence among elderly Caucasians and immunosuppressed individuals. MCC is either associated with a clonal integration of the Merkel cell polyoma virus into the host genome or with genomic alterations caused by chronic UV exposure. Tumors of either carcinogenesis show epithelial, neuroendocrine, and B-lymphoid lineage markers. HIV-infected African albinos have a higher risk of developing skin cancers, including MCC, in comparison with the general population. We report a case of MCC of the head in a young albino woman with a HIV/HTLV-1 coinfection. The patient also suffered from multiple squamous cell carcinomas of the scalp, face, lip, and ears, suggesting an UV carcinogenesis of MCC. The purpose of this case report is to emphasize the relationship between immunosuppression (HIV/HTLV-1 coinfection, chronic sun exposure, ocular-cutaneous albinism, pregnancy) and MCC. It highlights the importance of early diagnosis, dermatological screening with a risk-stratified surveillance, particularly in immunosuppressed albino patients in sub-Saharan Africa, and multidisciplinary management of this biologically unique cutaneous cancer.
Recurrent mutations in the basic domain of TWIST2 cause ablepharon macrostomia and Barber-Say syndromes
(Cell Press, 2015-07) Marchegiani, Shannon; Davis, Taylor; Tessadori, Federico; Van Haaften, Gijs; Brancati, Francesco; Hoischen, Alexander; Huang, Haigen; Valkanas, Elise; Pusey, Barbara; Schanze, Denny; Zerfas, Patricia M.; Zambruno, Giovanna; Kariminejad, Ariana; Sabbagh-Kermani, Farahnaz; Lee, Janice; Tsokos, Maria G.; Lee, Chyi-Chia R.; Ferraz, Victor; Da Silva, Eduarda Morgana; Stevens, Cathy A.; Roche, Nathalie; Bartsch, Oliver; Farndon, Peter; Bermejo-Sanchez, Eva; Brooks, Brian P.; Maduro, Valerie; Dallapiccola, Bruno; Ramos, Feliciano J.; Chung, Hon-Yin Brian; Le Caignec, Cedric; Martins, Fabiana; Mazzanti, Laura; Brunner, Han G.; Bakkers, Jeroen; Lin, Shuo; Malicdan, May Christine V.; Boerkoel, Cornelius F.; Gahl, William A.; De Vries, Bert B.A.; Van Haelst, Mieke M.; Zenker, Martin; Markello, Thomas C.; Venselaar, Hanka; Jacyk, Witold Kamil
Ablepharon macrostomia syndrome (AMS) and Barber-Say syndrome (BSS) are rare congenital ectodermal dysplasias characterized by similar clinical features. To establish the genetic basis of AMS and BSS, we performed extensive clinical phenotyping, whole exome and candidate gene sequencing, and functional validations. We identified a recurrent de novo mutation in TWIST2 in seven independent AMS-affected families, as well as another recurrent de novo mutation affecting the same amino acid in ten independent BSS-affected families. Moreover, a genotype-phenotype correlation was observed, because the two syndromes differed based solely upon the nature of the substituting amino acid: a lysine at TWIST2 residue 75 resulted in AMS, whereas a glutamine or alanine yielded BSS. TWIST2 encodes a basic helix-loop-helix transcription factor that regulates the development of mesenchymal tissues. All identified mutations fell in the basic domain of TWIST2 and altered the DNA-binding pattern of Flag-TWIST2 in HeLa cells. Comparison of wild-type and mutant TWIST2 expressed in zebrafish identified abnormal developmental phenotypes and widespread transcriptome changes. Our results suggest that autosomal-dominant TWIST2 mutations cause AMS or BSS by inducing protean effects on the transcription factor's DNA binding.
Chronic ulcerative stomatitis and lichen planus : just a coincidence or a direct link between the two diseases?
(Cornetis Publishing House, 2012) Jacyk, Witold Kamil; Fourie, Jeanine; Van Heerden, Willem Francois Petrus; witold.jacyk@up.ac.za
Chronic ulcerative dermatitis (CUS) is characterized by painful exacerbating and remitting oral erosions and ulcerations. A very characteristic direct immunofluorescence (DIF) pattern differentiates CUS from other immune-mediated oral vesiculo-erosive conditions. The clinical and histopathological features of CUS are very similar to erosive oral lichen planus. A middle-aged woman had CUS confirmed by DIF and chronic plantar ulceration. Histology of the lesion on the sole showed features of lichen planus (LP). DIF of the plantar lesion showed the same pattern as the oral lesion of CUS. The relationship between CUS and erosive (ulcerative) LP of the foot is discussed. Chloroquine improved the oral lesions while oral cyclosporine A ameliorated both oral and plantar lesions.
Carbamazepine-induced Stevens-Johnson syndrome sparing the skin previously affected by Herpes Zoster infection in a patient with Systemic Lupus Erythematosus : a reverse isotopic phenomenon
(Karger, 2010-05) Tenea, Daniela
The reverse isotopic response is a rarely encountered phenomenon. The spared lesions are various and mainly inflammatory in nature, with herpes zoster infection being the most common. A novel case of Stevens-Johnson syndrome triggered by carbamazepine sparing the skin area previously affected by herpes zoster infection in a 39-year-old Indian female with systemic lupus erythematosus is documented. Several features as well as possible pathomechanisms that bear discussion have emerged from this case documentation. These may be related to the virus immunity, the underlying autoimmune disease (systemic lupus erythematosus) and/or drug metabolism.
Heliotherapy : a South African perspective
(Health and Medical Publishing Group, 2010-11) Moosa, Yaaseen; Esterhuyse, D.J. (Daniel Johannes)
The research objective was to gather and collate data that will enable dermatologists to quantify exposure to solar radiation so that they can give accurate advice to patients using heliotherapy, thereby minimising harm from sun exposure. Other patients can also be advised regarding ultraviolet index (UVI) and sun safety. The concept of minimal erythema dose per hour (MED/h) may be useful in future research into solar radiation and its effects on skin cancer.
Revised nomenclature and classification of inherited ichthyoses : results of the first ichthyosis consensus conference in Sorèze 2009
(American Academy of Dermatology, 2010-10) Oji, Vinzenz; Tadini, Gianluca; Akiyama, Masashi; Bardon, Claudine Blanchet; Bodemer, Christine; Bourrat, Emmanuelle; Coudiere, Philippe; DiGiovanna, John J.; Elias, Peter; Fischer, Judith; Fleckman, Philip; Gina, Michal; Harper, John; Hashimoto, Takashi; Hausser, Ingrid; Hennies, Hans Christian; Hohl, Daniel; Hovnanian, Alain; Ishida-Yamamoto, Akemi; Jacyk, Witold Kamil; Leachman, Sancy; Leigh, Irene; Mazereeuw-Hautier, Juliette; Milstone, Leonard; Morice-Picard, Fanny; Paller, Amy S.; Richard, Gabriele; Schmuth, Matthias; Shimizu, Hiroshi; Sprecher, Eli; Van Steensel, Maurice; Taieb, Alain; Toro, Jorge R.; Vabres, Pierre; Vahlquist, Anders; Williams, Mary; Traupe, Heiko
BACKGROUND: Inherited ichthyoses belong to a large, clinically and etiologically heterogeneous group of mendelian disorders of cornification, typically involving the entire integument. Over the recent years, much progress has been made defining their molecular causes. However, there is no internationally accepted classification and terminology. OBJECTIVE: We sought to establish a consensus for the nomenclature and classification of inherited ichthyoses. METHODS: The classification project started at the First World Conference on Ichthyosis in 2007. A large international network of expert clinicians, skin pathologists, and geneticists entertained an interactive dialogue over 2 years, eventually leading to the First Ichthyosis Consensus Conference held in Sore`ze, France, on January 23 and 24, 2009, where subcommittees on different issues proposed terminology that was debated until consensus was reached. RESULTS: It was agreed that currently the nosology should remain clinically based. ‘‘Syndromic’’ versus ‘‘nonsyndromic’’ forms provide a useful major subdivision. Several clinical terms and controversialdisease names have been redefined: eg, the group caused by keratin mutations is referred to by the umbrella term, ‘‘keratinopathic ichthyosis’’eunder which are included epidermolytic ichthyosis, superficial epidermolytic ichthyosis, and ichthyosisCurth-Macklin. ‘‘Autosomal recessive congenital ichthyosis’’ isproposed as anumbrella term for the harlequin ichthyosis, lamellar ichthyosis, and the congenital ichthyosiform erythroderma group. LIMITATIONS: As more becomes known about these diseases in the future, modifications will be needed. CONCLUSION: We have achieved an international consensus for the classification of inherited ichthyosis that should be useful for all clinicians and can serve as reference point for future research. ( J Am Acad Dermatol 2010;63:607-41.)
Pagetoid reticulosis with CD30 positivity and cytotoxic/suppressor cells
(Blackwell, 2007-08) Jacyk, Witold Kamil; Grayson, Wayne; Dinkel, Jurgen Erich; Requena, Luis
Pagetoid reticulosis (PR), also named Woringer-Kolopp disease, is a low-grade primary cutaneous T-cell lymphoma that usually presents as a solitary, slowly enlarging erythematous or hyperkeratotic plaque on the distal areas of the extremities. Histopathologically, it is characterized by a dense, band-like infiltrate of atypical lymphocytes with prominent epidermotropism within a hyperplastic epidermis, and immunophenotypic studies show in most cases, a CD4-positive T-helper phenotype for the neoplastic lymphocytes. We describe an African man with a more than 20-year history of an acral lesion of PR, which was histopathologically characterized by lymphocyte immunophenotype consisting of CD8- and CD30-positive cells. We discuss the differential diagnosis with other primary cutaneous lymphoproliferative disorders showing similar immunophenotype. This case shows that CD30-positive PR should be included as a rare variant within the spectrum of CD30-positive primary cutaneous lymphoproliferative disorders. As in other primary cutaneous CD30-positive lymphoproliferative processes, lesions of CD30-positive PR show an indolent course and a benign biological behavior. Histopathologically, it shows a prominent infiltrate of atypical lymphocytes within a hyperplastic epidermis. Immunophenotypic studies in lesions of PR have led to the recognition of different phenotypes for the large atypical epidermotropic lymphocytes. The CD4-positive T-helper phenotype appears the most common.

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