Disseminated protothecosis: Case report and review of the literature.

BACKGROUND: Human protothecosis is an uncommon infection caused by Prototheca spp that rarely infects humans. AIM: Description of a rare disease and a review of its articles. MATERIALS AND METHODS: We reported a 24-year-old man who presented with red-brown papules and plaques on the trunk's lateral side. We reviewed the literature about disseminated protothecosis and reported our experience with a patient with protothecosis between 2021 and 2023. RESULTS: Overall, 54 cases of disseminated protothecosis were evaluated, 39 were due to P. wickerhamii, 12 were due to P. zopfii (22.2%), and three were due to Prototheca spp. We found that males were more affected (37 cases, 68.5%) than females (16 cases, 29.6%). The mean age of patients was 39.53 ± 22.48 years. However, disseminated protothecosis can affect people of any age (1-80 years). In contrast to P. wickerhamii, which causes blood, skin, brain, and gastrointestinal tract infections, P. zopfii was mainly found in the blood (7/22) and did not have a significant difference in the mortality rate (P = 0.11). DISCUSSION: Disseminated protothecosis is a rare disease in immunocompromised patients but is generally rarer in immunocompetent hosts. Several underlying disorders include immunocompromised patients, prolonged application of steroids, diabetes mellitus, malignancies, organ transplantation, AIDS, and surgeries. Amphotericin B has been the most effective agent for protothecosis and is reserved for visceral and disseminated infections. Regarding localized cutaneous types, excision or surgical debridement is used. CONCLUSION: Mulberry's appearance and appropriate cultural environments are helpful in diagnosing it.

Histopathologic Spectrum of Findings Associated With Tattoos: Multicenter Study Series of 230 Cases.

IMPORTANCE: Reactions to tattoo may simulate common dermatosis or skin neoplasms. Histopathology allows diagnosis and helps determining the level and degree of inflammation associated, consequently orientating treatment. OBJECTIVE: To describe the histological features found in biopsies of cutaneous reactions to tattoo. DESIGN: This study was designed as a multicenter case series. SETTING: All consecutive histopathological samples of tattoos referred from 1992 to 2019 to the Hospital General de Catalunya, Hospital Germans Trias i Pujol, and a private practice, all in Barcelona, Spain, and from the Kempf und Pfaltz Histologische Diagnostik in Zurich, Switzerland were retrieved from the files. PARTICIPANTS AND EXPOSURE: The inclusion criteria were all cosmetic/permanent makeup, artistic/professional, and traumatic tattoos associated with either inflammatory reactions alone and/or with tumors and/or infections. Exclusion criteria were cases without any associated pathologic finding in the place of the ink, amalgam tattoos, and medical or temporary tattoos. MAIN OUTCOMES AND MEASURES: In all patients, clinical features (age, sex, location, tattoo color, and presentation) were recorded. Histological features evaluated included ink color, associated tumors or infections, and inflammatory reaction pattern. Inflammation was graded in low to moderate or severe. RESULTS: From 477 biopsies diagnosed as tattoos, 230 cases from 226 patients met the inclusion criteria. Samples corresponded to 107 male and 120 female subjects and 3 of unknown gender. Median age was 39 years (ranging from 9 to 84 years). Fifty-three samples were referred from centers in Spain and 177 from the center in Switzerland. The series was analyzed in 2 parts: tattoos associated only with inflammatory reactions (117/230) and tattoos associated with tumors or infections (113/230). The most common form of inflammatory pattern associated with tattoo was the fibrosing reaction (79/117, 68%), followed by granulomatous reaction (56/117, 48%), lichenoid reaction (33/117, 28%), epithelial hyperplasia (28/117, 24%), pseudolymphoma (27/117, 23%) and spongiotic reaction (27/117, 23%). Combined features of 2 or more types of inflammatory patterns were seen in 64% cases. CONCLUSIONS AND RELEVANCE: Our series confirms that cutaneous reactions to tattoos are polymorphous. Inflammation tends to present with combined patterns. Infections are tending to decline, and pathologic findings are not specific to ink color or clinical features.

Cutaneous manifestations of patients with Human Immunodeficiency Virus (HIV) Infection: A retrospective review of a tertiary referral centre with clinicopathological correlation.

INTRODUCTION: The majority of patients with Human Immunodeficiency Virus (HIV) will have cutaneous manifestation during their disease course. We report the spectrum of cutaneous manifestations and clinicopathological concordance in the diagnosis of skin diseases in patients with HIV. METHODS: A retrospective review of all cutaneous manifestations of HIV-infected patients with skin biopsy-proven histopathological confirmation, treated in the University of Malaya Medical Centre, from 2016 till 2018, was performed. Clinical characteristics and histopathological correlation of these patients were reviewed. RESULTS: A total of 38 cases were included where the median age was 40.5 (interquartile range (IQR) 13.3). The median duration of HIV diagnosis to the development of skin disease was 3 years (IQR 7.8). Majority of our patients were male (89.5%, n = 34), and the commonest mode of transmission is men who have sex with men (36.8%, n = 14). Most patients (92.1%, n = 35) had Acquired Immunodeficiency Syndrome when they presented with skin diseases, predominantly non-infectious types (51.4%, n = 19). Commonest skin diseases include eczema (n = 7) and pruritic papular eruption of HIV (n = 6). Papules and plaques were the commonest morphology for both infectious and non-infectious skin diseases. Duration of HIV diagnosis (P = 0.018) and non-compliance to Highly Active Antiretroviral Therapy (HAART) (P = 0.014) were significantly associated with the development of non-infectious skin diseases. Overall, clinicopathological concordance was 84.2% in our centre. CONCLUSION: A wide spectrum of cutaneous diseases can occur in HIV patients depending on the degree of immunosuppression. skin biopsy along with appropriate stains, and microbiological cultures are important in helping clinicians clinch the right diagnosis.

Refractory Human Cutaneous Protothecosis.

A 67-year-old Scottish woman presented to her general practitioner with a subcentimeter lump between her shoulder blades. The lump was suspected to be an epidermal cyst and was excised. The patient had a history of controlled diabetes. Most summers, she spent a month near a beach resort in Mexico. The lump reappeared after 6 months within the scar area and was re- excised. Both skin excisions were performed in the primary care setting without histologic assessment.

Complicated Posterior Cervical Skin and Soft Tissue Infections at a Single Referral Center.

BACKGROUND: Although the incidence and mortality of complicated skin and soft tissue infections have decreased, this infection is still relatively frequent and can be associated with lethal complications. In this study, the authors present our clinical experience of patients with complicated posterior cervical skin and soft tissue infections (CPCSSTIs) diagnosed and treated in a reconstructive unit in northeastern China. METHODS: A retrospective chart review of patients diagnosed with CPCSSTIs from January 2009 to December 2018 was performed. To make the results objective and convincing, a data analysis was performed relating to demographic characteristics, clinical presentation, predisposing factor, bacterial culture, laboratory and radiographic evaluations, diagnostic clues, management, and complications as well as the clinical course and outcome. RESULTS: During the ten-year period, there were 174 consecutive patients admitted to our reconstructive center with final diagnosis of CPCSSTIs included. All the patients were adults, and the majority were male (67.2%). The patient's mean age was 51.3 years (range, 15-88 years). There were 114 patients (65.5%) that had associated systemic diseases, with diabetes mellitus (40.2%) as the most common predisposing factor. Common presented clinical symptoms were pain (90.8%), swelling (85.1%), and erythema (77%) of the neck. Surgical treatment was performed in all the patients, and most of them (83.9%) received the first surgery within 24 h. The most commonly isolated pathogen was Staphylococcus aureus (30%). Vancomycin (21.3%) was the most commonly used antibiotics, followed by cefepime (18.4%). All the patients survived and were discharged with a mean duration of hospitalization of 28.7 days. Those patients with predisposing factors (31.4 ± 12.35 days) or complications (41.0 ± 12.5 days) tended to have a longer hospital stay. The mean total costs of admission per patient were 47 644 RMB. CONCLUSION: This study highlights the high cost burden of CPCSSTI patients. Those patients with predisposing factors or complications tended to have a longer hospital stay.

Reflectance confocal microscopy for the diagnosis of skin infections and infestations.

Reflectance confocal microscopy (RCM) is a noninvasive real-time imaging technique that has been widely used for the diagnosis of skin cancer. More recently, it has been reported as a useful tool for the diagnosis and management of several inflammatory and infectious skin disorders. This article provides an overview of the current available applications of RCM use in cutaneous infections and infestations. PubMed was used to search the following terms in various combinations: reflectance confocal microscopy, skin, hair, nail, infection, parasitosis, mycosis, virus, bacteria. All papers were accordingly reviewed. In most cutaneous infections or infestations, the main alterations are found in the epidermis and upper dermis, where the accuracy of confocal microscopy is nearly similar to that of histopathology. The high resolution of this technique allows the visualization of most skin parasites, fungi, and a few bacteria. Although viruses cannot be identified because of their small size, viral cytopathic effects can be observed on keratinocytes. In addition, RCM can be used to monitor the response to treatment, thereby reducing unnecessary treatments.

Human genetic dissection of papillomavirus-driven diseases: new insight into their pathogenesis.

Human papillomaviruses (HPVs) infect mucosal or cutaneous stratified epithelia. There are 5 genera and more than 200 types of HPV, each with a specific tropism and virulence. HPV infections are typically asymptomatic or result in benign tumors, which may be disseminated or persistent in rare cases, but a few oncogenic HPVs can cause cancers. This review deals with the human genetic and immunological basis of interindividual clinical variability in the course of HPV infections of the skin and mucosae. Typical epidermodysplasia verruciformis (EV) is characterized by ß-HPV-driven flat wart-like and pityriasis-like cutaneous lesions and non-melanoma skin cancers in patients with inborn errors of EVER1-EVER2-CIB1-dependent skin-intrinsic immunity. Atypical EV is associated with other infectious diseases in patients with inborn errors of T cells. Severe cutaneous or anogenital warts, including anogenital cancers, are also driven by certain α-, γ-, µ or ν-HPVs in patients with inborn errors of T lymphocytes and antigen-presenting cells. The genetic basis of HPV diseases at other mucosal sites, such as oral multifocal epithelial hyperplasia or juvenile recurrent respiratory papillomatosis (JRRP), remains poorly understood. The human genetic dissection of HPV-driven lesions will clarify the molecular and cellular basis of protective immunity to HPVs, and should lead to novel diagnostic, preventive, and curative approaches in patients.

Cytologic, histologic, microbiologic, and electron microscopic characterization of a canine Prototheca wickerhamii infection.

An adult dog was presented for chronic cough and a recent development of ulcerated, erythematous nares with nasal discharge. Cytology of enlarged peripheral lymph nodes revealed many intracellular and extracellular organisms. These round or rarely oval organisms measured approximately 5-9 µm in diameter and frequently contained several globular structures, ranging from deeply basophilic to magenta. A thin, clear halo was present. Smaller 1-2 µm, magenta forms were also observed. Fungal culture yielded small, wet, raised, irregularly shaped, white to pale tan colonies. Microbiologic staining of cultured material revealed features suggestive of algae. Histopathology of the lymph nodes revealed marked granulomatous inflammation with intralesional algal organisms suggestive of Prototheca. Electron microscopic findings were also consistent with protothecosis. Polymerase chain reaction, followed by direct DNA sequencing, identified the organism as Prototheca wickerhamii. A brief literature review discussing protothecosis in veterinary medicine is included.

[New aspects in the histopathology of infectious skin diseases]. / Neue Aspekte zur Histopathologie bei Hautinfektionen.

BACKGROUND: An infectious pathogenesis should always be considered in inflammatory infiltrates in the skin. While some organisms can be recognized on hematoxylin-eosin staining (e.g. yeasts, leishmania), histochemical and immunohistochemical stainings are available for others. OBJECTIVES: If no organisms are seen in a section, the diagnosis of an infection cannot be made with surety, but the pattern of the inflammatory infiltrate can still be suggestive of an infectious process. New or little-known reaction patterns and difficulties in differential diagnosis will be demonstrated. MATERIALS AND METHODS: Selective literature review and analysis of individual cases. RESULTS: Studies using molecular techniques to identify organisms in biopsy specimens have helped to better characterize the histomorphological spectrum of skin infiltrates in infectious skin diseases. Apart from unusual herpes simplex and varicella zoster infections, the histopathology of coxsackie virus and measles exanthem, borreliosis, syphilis, and of cutaneous leishmaniasis is demonstrated. For numerous organisms, molecular tests have been established that can be used on the formalin-fixed, paraffin-embedded material. CONCLUSIONS: Selected skin infections demonstrate the broad histomorphological spectrum of skin infiltrates induced by infectious organisms. It is important for histopathologists to know which reaction pattern requires them to alert the clinician to necessary ancillary diagnostics (culture, serology) and when to consider molecular diagnostics to be performed on the biopsy specimen.

Cutaneous protothecosis in kidney transplant recipient

Abstract Protothecosis is a rare condition caused by the aclorophylated algae of the genus Prototheca. In humans, protothecosis, caused mainly by P. wickerhamii, manifests itself in three forms: cutaneous, articular and systemic. It can occur in both immunocompetent and immunosuppressed individuals, being much more common in the latter. We present a new case of protothecosis in Brazil in a kidney transplant recipient.

Comparison between organismal staining on histology and tissue culture in the diagnosis of cutaneous infection: A retrospective study.

BACKGROUND: In instances of suspected cutaneous infection, the standard of care includes obtaining skin biopsy specimens for histology and tissue culture. Few studies have compared the clinical utility of each test. OBJECTIVE: To assess the concordance of results between tissue culture and histology, as well as the clinicopathologic features that may influence the diagnostic yield of each test. METHODS: A retrospective review of all patients who underwent skin biopsy for histology and tissue culture at New York University from 2013 through 2018. RESULTS: Of 179 patients, 10% had positive concordance, 21% had positive tissue culture only, and 7% had positive histology only. We calculated a kappa correlation coefficient of 0.25 between histology and tissue culture (reference, 0.21-0.39 indicates minimal agreement). Histology exhibited higher sensitivity in detecting fungi, whereas tissue culture was more sensitive in identifying Gram-negative bacteria. Antimicrobial use before biopsy led to significantly fewer positive cultures (37.5% vs 71%; P = .023) in patients ultimately diagnosed with infection. LIMITATIONS: This study was conducted at a single institution, thereby restricting its broad applicability. The lack of a validated criterion standard to diagnose infection also limits interpretation of the results. CONCLUSION: Tissue culture and histopathology often yield discordant results. Dermatologists should recognize specific limitations, yet high clinical utility in special circumstances, of tests when approaching cases of suspected infection.

Emergence of Fungal-Like Organisms: Prototheca.

The genus Prototheca consists of achlorophyllic algae that are ubiquitous in the environment and animal intestines. However, this organism has forfeited its photosynthetic ability and switched to parasitism. In 1894, Krüger described two microorganisms isolated in Germany from mucous flux of Tilia and Ulmus spp., namely Prototheca moriformis and P. zopfii. Based on their yeast-like colony morphology, Krüger classified these organisms as fungi. The genus is now included within the class Trebouxiophyceae, order Chlorellales, and family Chlorellaceae. Historically, protothecosis and infections caused by green algae have been studied in the field of medical mycology. Prototheca spp. have been found to colonize human skin, fingernails, the respiratory tract, and digestive system. Although human infection by Prototheca is considered rare, an increase in infections has been noted among immunosuppressed patients, those on corticosteroid treatment, or both. Moreover, the first human outbreak of protothecal algaemia and sepsis was recently reported in a tertiary care chemotherapy oncology unit in 2018. Prototheca is also a causative pathogen of bovine disease. Prototheca zopfii and P. blaschkeae are associated with bovine mastitis, which causes a reduction in milk production and secretion of thin, watery milk containing white flakes. Economic losses are incurred either directly via reduced milk production and premature culling of affected animals or indirectly as a result of treatment and veterinary care expenses. Thus, knowledge of this fungal-like pathogen is essential in human and veterinary medicine. In this mini-review, I briefly introduce human and animal protothecoses.

The utility and challenges of histopathologic evaluation in the diagnosis of nonmalignant skin ulcers.

Histopathologic evaluation of cutaneous ulcers is indicated when the clinical diagnosis is unclear or when ulcers have not responded to standard of care. Many nonmalignant skin ulcers lack specific histologic findings on biopsy and pose a diagnostic challenge. While the usefulness of skin biopsies to diagnose underlying malignancy in ulcerated lesions has been demonstrated in previous studies, their utility in the diagnosis of ulcers of other etiologies has not been reported. We conducted a retrospective study of 45 nonmalignant ulcer biopsies in a 3-year period to compare the histologic diagnosis with the final diagnosis. Additionally, we assessed the diagnostic concordance among three blinded dermatopathologists when reviewing these cases. The leading histologic diagnosis from each of the three observers agreed with the final clinical diagnosis, on average, for 29.6% of the cases (average pairwise kappa = 0.15). Inflammatory ulcers had the lowest concordance between the observers and final diagnosis with an average of 26.0% of cases (average pairwise kappa = 0.06). The observers agreed with each other for 35.6% of the cases (Fleiss' kappa = 0.32). The highest agreement among observers was in the vascular/vasculopathic category (50%, Fleiss' kappa = 0.44). Our results indicate that skin biopsies alone are useful in the evaluation of nonmalignant ulcers to rule out other conditions (e.g. neoplasm) but frequently not sufficient to establish a definitive diagnosis. Additional clinicopathologic correlation is necessary in the final assessment of nonmalignant ulcers to determine the diagnosis. Future research endeavors should explore alternative approaches to more efficiently diagnose nonmalignant skin ulcers.

Protective and pathogenic roles of resident memory T cells in human skin disorders.

The human skin is populated by recirculating T cells and skin-sessile resident memory T cells (TRM). Skin TRM are constructed during immune responses against antigens that the host immune system encounters in the skin. TRM persist in the same sites for a long time and play important protective roles in skin immune responses in collaboration with other skin-composing cells such as dendritic cells and keratinocytes. These TRM with strong effector functions possibly also engender skin inflammatory disorders. Since human skin T cells, especially TRM, are phenotypically distinct from T cells in the blood circulation, T cells residing in the skin should be directly investigated, without presuming from the activities of blood T cells, in order to understand the functional characteristics of skin T cells in skin disorders. This review summarizes the features of human skin TRM and reviews the immunopathological involvement of TRM in human skin disorders such as infectious disease, inflammatory skin disease, and malignant skin tumors.

Skin diseases of the breast and nipple: Inflammatory and infectious diseases.

Certain dermatologic conditions are unique to the breast and nipple, whereas others may incidentally involve these structures. All require a nuanced approach to diagnosis and treatment because of the functional, sexual, and aesthetic importance of this area. The lactating patient requires special management because certain treatment options are contraindicated. All dermatologic conditions involving the breast and nipple require careful evaluation because malignancy of the breast can be mistaken for a benign condition or may trigger the development of certain dermatologic conditions. The second article in this continuing medical education series reviews common and uncommon inflammatory and infectious conditions of the breast and nipple and provides insight into both the diagnosis and the treatment of this heterogeneous group of diseases. For the purposes of this article, these conditions are divided into 4 distinct categories: 1) dermatitis; 2) radiation-induced changes; 3) mastitis; and 4) miscellaneous dermatologic conditions of the breast and nipple.

Spatio-temporal dynamics and aetiology of proliferative leg skin lesions in wild British finches.

Proliferative leg skin lesions have been described in wild finches in Europe although there have been no large-scale studies of their aetiology or epizootiology to date. Firstly, disease surveillance, utilising public reporting of observations of live wild finches was conducted in Great Britain (GB) and showed proliferative leg skin lesions in chaffinches (Fringilla coelebs) to be widespread. Seasonal variation was observed, with a peak during the winter months. Secondly, pathological investigations were performed on a sample of 39 chaffinches, four bullfinches (Pyrrhula pyrrhula), one greenfinch (Chloris chloris) and one goldfinch (Carduelis carduelis) with proliferative leg skin lesions and detected Cnemidocoptes sp. mites in 91% (41/45) of affected finches and from all species examined. Fringilla coelebs papillomavirus (FcPV1) PCR was positive in 74% (23/31) of birds tested: a 394 base pair sequence was derived from 20 of these birds, from all examined species, with 100% identity to reference genomes. Both mites and FcPV1 DNA were detected in 71% (20/28) of birds tested for both pathogens. Histopathological examination of lesions did not discriminate the relative importance of mite or FcPV1 infection as their cause. Development of techniques to localise FcPV1 within lesions is required to elucidate the pathological significance of FcPV1 DNA detection.

Alternative uses of dermoscopy in daily clinical practice: An update.

Dermoscopy is a noninvasive diagnostic tool that is currently being used for neoplastic skin lesions, several inflammatory and infectious diseases, and skin appendage disorders. As the clinical applications of dermoscopy beyond pigmented lesions are constantly increasing, the aim of this article is to provide an update on this topic. This comprehensive review substantiates how several diseases may show peculiar dermoscopy features so as to enhance the diagnosis and avoid (in selected cases) unnecessary histologic confirmation. In other cases, dermoscopy features may be shared with other conditions, with the advantage of narrowing down the differential diagnosis by ruling out those dermatoses with similar clinical aspect but different dermoscopic presentation.

Clinicopathological features and course of cutaneous protothecosis.

BACKGROUND: Protothecosis is an uncommon infection caused by the achlorophyllic algae found more commonly in tropical areas. Only a limited number of cases have been reported. OBJECTIVE: We aimed to evaluate the clinicopathological features and treatment outcomes of cutaneous protothecosis. METHODS: We retrospectively identified 20 pathology-confirmed cases of cutaneous protothecosis based on skin biopsies in two tertiary medical centres in Taiwan from 1997 to 2015. RESULTS: The age of the patients at the time of diagnosis ranged from 48 to 85 years (mean age of 74 years). All lesions developed on the limbs. Twelve (60%) patients had adrenal insufficiency, but no patients had active malignancy at diagnosis. Interestingly, four (20%) patients had concurrent scabies infestation. Clinically, most lesions were erythematous plaques studded with punctate ulcers. Microscopically, the most common finding was granulomatous inflammation. Nineteen (95%) cases were successfully treated with itraconazole for 14-148 days with only one case of recurrence. Concomitant scabies should be suspected if pruritus is recalcitrant despite itraconazole treatment. CONCLUSION: Despite its rarity, cutaneous protothecosis has become more significant due to an increased prevalence of immunocompromised individuals. Steroid overuse or iatrogenic adrenal insufficiency predisposes individuals to high-risk infections. Neglecting the disease leads to a chronic and incurable state. Protothecosis should be suspected in chronic eczematous and ulcerative plaques on the limbs refractory to conventional antibacterial and antiviral treatments, especially in patients with adrenal insufficiency. Clinical suspicion should be confirmed by skin biopsies, and confirmed cases can be successfully treated with itraconazole.

[Practices in infectious pathology in France in 2015. Results of the national survey]. / Pratique de la pathologie infectieuse en France en 2015. Résultats d'un questionnaire national.

Pathologists have been, are and will be always implicated in the diagnosis of infectious and tropical diseases. The resurgence of opportunistic infections due to the development of immunosuppressive drugs, the increase of migratory involvements draining tropical infections and the last epidemics spotlight the importance of pathologists in the field of infectious diseases. However, cancer is nowadays the first preoccupation of pathologists, which is constantly subject to evaluate diagnostic and prognostic markers and factors predictive to targeted therapy response or immunotherapy. As tumor pathology, infectious diseases require more sophisticated and rapidly changing complementary techniques, appraisals and perhaps a national network of diagnosis. The infectious pathology club committee carries out here a census of methods used in the diagnosis of infectious diseases in France in 2015 and particularly the different techniques used by laboratories to perform infectious diseases diagnosis. This will lay down the foundation of a future national organization of the infectious pathology in providing efficient services (diagnostic support, complementary tools) for the community of French pathologists in this specific domain of competence.