Infections in the era of immunobiologicals.

Immunobiologicals represent an innovative therapeutic option in dermatology. They are indicated in severe and refractory cases of different diseases when there is contraindication, intolerance, or failure of conventional systemic therapy and in cases with significant impairment of patient quality of life. The main immunobiologicals used in dermatology basically include inhibitors of tumor necrosis factor-alpha (anti-TNF), inhibitors of interleukin-12 and -23 (anti-IL12/23), inhibitors of interleukin-17 and its receptor (anti-IL17), inhibitors of interleukin-23 (anti-IL23), rituximab (anti-CD20 antibody), dupilumab (anti-IL4/IL13) and intravenous immunoglobulin. Their immunomodulatory action may be associated with an increase in the risk of infections in the short and long term, and each case must be assessed individually, according to the risk inherent to the drug, the patient general condition, and the need for precautions. This article will discuss the main risks of infection associated with the use of immunobiologicals, addressing the risk in immunocompetent and immunosuppressed patients, vaccination, fungal infections, tuberculosis, leprosy, and viral hepatitis, and how to manage the patient in the most diverse scenarios.

Follicular mycosis fungoides: Clinicohistopathologic features and outcomes in a series of 12 Chinese cases.

Background Follicular mycosis fungoides is a distinct variant of mycosis fungoides with a broad clinical spectrum. Recently, many studies have indicated that follicular mycosis fungoides should be divided into different subtypes with disparate prognoses. Objective To define the clinicohistopathologic features and outcomes of follicular mycosis fungoides and to identify risk factors that may be related to the prognosis of Chinese patients with follicular mycosis fungoides. Materials and methods We conducted a single-centre retrospective study and reviewed the clinical, histopathologic and immunophenotypic data of 12 patients diagnosed with follicular mycosis fungoides between 2009 and 2020 in the Department of Dermatology of West China Hospital of Sichuan university. Results A total of 12 patients (seven males and five females) with a mean age of 30 ± 14 years (age range 16-55 years) were included. Scalp and face were the most common involved sites (100%). Follicular papules, acneiform lesions, plaques, and nodules, were the main clinical presentations. Histopathological findings were consistent with the classic manifestations of follicular mycosis fungoides, including folliculotropism, perifollicular and intrafollicular lymphocytic infiltrates and mucinous degeneration. Interferon α-1b was the most common treatment. Four patients died of follicular mycosis fungoides in three years. Notably, immunohistochemical analysis revealed a decreased number of CD20+ cells in the deceased patients. Limitations This is a retrospective evaluation with a small number of cases; further prospective studies are warranted to support our inferences. Conclusion Our patients were much younger than in previous studies. The observed difference in this cohort may be explained by race, in addition to the limited number of cases. A decreased number of B cells might be associated with a poor prognosis, and more studies are necessary to discover the role of B cells in follicular mycosis fungoides as well as in mycosis fungoides.

Lobomycosis: exuberant presentation with malignant transformation

Abstract Lobomycosis is a chronic granulomatous infection caused by the yeast Lacazia loboi, typically found in tropical and subtropical geographical areas. Transmission occurs through traumatic inoculation into the skin, especially in exposed areas, of men who work in contact with the soil. Lesions are restricted to the skin and subcutaneous tissue, with a keloid-like appearance in most cases. The occurrence of squamous cell carcinoma on skin lesions with a long evolution is well known; however, there are scarce reports of lobomycosis that developed into squamous cell carcinoma. The authors report a patient from the Brazilian Amazon region, with lobomycosis and carcinomatous degeneration, with an unfavorable outcome, due to late diagnosis.

Lobomycosis: exuberant presentation with malignant transformation.

Lobomycosis is a chronic granulomatous infection caused by the yeast Lacazia loboi, typically found in tropical and subtropical geographical areas. Transmission occurs through traumatic inoculation into the skin, especially in exposed areas, of men who work in contact with the soil. Lesions are restricted to the skin and subcutaneous tissue, with a keloid-like appearance in most cases. The occurrence of squamous cell carcinoma on skin lesions with a long evolution is well known; however, there are scarce reports of lobomycosis that developed into squamous cell carcinoma. The authors report a patient from the Brazilian Amazon region, with lobomycosis and carcinomatous degeneration, with an unfavorable outcome, due to late diagnosis.

Phototherapy as a treatment of early-stage mycosis fungoides and predictive factors for disease recurrence: A 17-year retrospective study.

BACKGROUND: Mycosis fungoides is the most common form of cutaneous T-cell lymphoma. Narrowband ultraviolet B and psoralen and ultraviolet A are effective treatment options, but studies of their treatment efficacy and disease relapse remain limited. OBJECTIVES: This study aimed (1) to determine the efficacy of narrowband ultraviolet B and psoralen and ultraviolet A as a treatment for early-stage mycosis fungoides and explore the predictive factors for complete remission and (2) to determine the relapse rate and analyze their predictive factors, including the utility of maintenance therapy. METHODS: This was a retrospective cohort study consisting of 61 patients with early-stage mycosis fungoides (IA - IB) treated with narrowband ultraviolet B or psoralen and ultraviolet A as the first-line therapy from January 2002 to December 2018 at the Division of Dermatology, Ramathibodi Hospital, Bangkok, Thailand. Cox regression analysis and Kaplan-Meier survival curve were performed for the main outcomes. RESULTS: A complete remission was achieved by 57 (93.5%) patients. The median time to remission was 7.80 ± 0.27 months. Types of phototherapy (narrowband ultraviolet B or psoralen and ultraviolet A), age and gender did not associate with time to remission, while the presence of poikiloderma and higher disease stage led to a longer time to remission. The cumulative incidence of relapse was 50.8%. The median time to relapse was 24.78 ± 5.48 months. In patients receiving phototherapy during the maintenance period, a treatment duration longer than six months was associated with a significantly longer relapse-free interval. CONCLUSION: Narrow-band-ultraviolet B and psoralen and ultraviolet A are effective treatment options for early-stage mycosis fungoides. Maintenance treatment by phototherapy for at least six months seems to prolong remission.

Thymocyte selection-associated high-mobility group box as a potential diagnostic marker differentiating hypopigmented mycosis fungoides from early vitiligo: A pilot study.

BACKGROUND: Hypopigmented mycosis fungoides is a rare variant of mycosis fungoides that may mimic many benign inflammatory hypopigmented dermatoses, and as yet there is no identified marker to differentiate between them. AIM: The aim of this study was to study the expression of thymocyte selection-associated high-mobility group box (TOX) in hypopigmented mycosis fungoides and one of its inflammatory mimickers (early active vitiligo) to assess its potential as a differentiating diagnostic marker. METHODS: A case-control study was done using immunohistochemical analysis of TOX expression in 15 patients with hypopigmented mycosis fungoides and 15 patients with early active vitiligo. Immunohistochemical analysis was done via a semi-quantitative method and an image analysis method. RESULTS: Hypopigmented mycosis fungoides showed a statistically significant higher expression of TOX than early active vitiligo. The expression of TOX was positive in a majority of hypopigmented mycosis fungoides cases (14 cases, 93.3%), while only one case (6.7%) of vitiligo was weakly positive. TOX also displayed 93.3% sensitivity and specificity, with a cut-off value of 1.5. LIMITATIONS: This was a pilot study testing hypopigmented mycosis fungoides against only a single benign inflammatory mimicker (early vitiligo). Other benign mimickers were not included. CONCLUSION: Our findings showed that TOX expression can differentiate hypopigmented mycosis fungoides from early active vitiligo which is one of its benign inflammatory mimickers, with a high degree of sensitivity and specificity.

A unique case of borderline lepromatous leprosy with psoriasis-like lesions all over the body and mycosis fungoides-like lesions on the face.

Clinical manifestations of leprosy are various and may resemble other skin diseases. Skin lesions of leprosy mimicking psoriasis and mycosis fungoides (MF) that simultaneously occurs in one patient are rare. We reported a unique case of borderline lepromatous (BL) leprosy with severe reversal reaction manifested as psoriasis-like lesions and MF-like lesions in a 43-year-old-man. Psoriasis-like lesions all over the body accompanied by plaques and tumor-like lesions mimicking MF on the face could be found in this patient. Histopathological examination on an MF-like lesion from the face and psoriasis-like lesions from the posterior trunk and lower extremities revealed granulomatous reaction with epithelioid cells, Langhans giant cells, and foam cells which supported the diagnosis of BL leprosy. The patient was treated with multidrug therapy multibacillary (MDT-MB) regimen and 40 mg prednisone daily which was tapered off. Clinical improvement was observed on the 32nd day of observation as psoriasis-like and MF-like lesions became hyperpigmented macules and plaques, respectively. Due to the rarity of the multitype skin lesions of leprosy in one patient, a diagnosis of leprosy should be suspected by the clinicians in any patients with previously described skin disorders, especially in an endemic area.

Acquired disorders with hypopigmentation: A clinical approach to diagnosis and treatment.

Acquired hypopigmented skin changes are commonly encountered by dermatologists. Although hypopigmentation is often asymptomatic and benign, occasional serious and disabling conditions present with cutaneous hypopigmentation. A thorough history and physical examination, centered on disease distribution and morphologic findings, can aid in delineating the causes of acquired hypopigmented disorders. The second article in this 2-part continuing medical education series focuses on conditions with a hypopigmented phenotype. Early diagnosis and appropriate management of these disorders can improve a patient's quality of life, halt disease progression, and prevent irreversible disability.

Granulomatous slack skin syndrome: Report of a unique case.

Granulomatous slack skin syndrome is a rare variant of cutaneous T-cell lymphoma (mycosis fungoides). It is characterized clinically by redundant skin folds, which show a predilection towards flexural areas such as the axilla and the groin. Histologically, it shows a granulomatous T-cell infiltrate and loss of elastic tissue. It has an indolent but progressive course; and is usually refractory to treatment. We report a unique case of slack skin syndrome, sparing the classical sites with rapid and unusual involvement of non-intertriginous areas.

Hodgkin's lymphoma arising in a case of mycosis fungoides: An unusual association.

Mycosis fungoides is a cutaneous T-cell lymphoma with a high risk for developing secondary malignancies, especially B-cell lymphoproliferative disorders. About 40 cases of Hodgkin's lymphoma associated with mycosis fungoides have been reported in literature till date. We report a case of a 35-year-old gentleman who presented with intensely itchy reddish lesions all over the body. Multiple skin biopsies taken from the lesions on scalp and back confirmed the clinical diagnosis of mycosis fungoides. While on treatment, he presented with multiple bilateral cervical, axillary and inguinal lymphadenopathy 9 years after the primary diagnosis of mycosis fungoides. Excision biopsy of a cervical lymph node revealed partial effacement of architecture by a tumor comprising polymorphous background. Histopathology and immunohistochemistry revealed a diagnosis of Hodgkin's lymphoma - nodular sclerosis subtype. The patient was started on chemotherapy for stage IV Hodgkin's lymphoma. Our case emphasizes the importance of keeping secondary Hodgkin's lymphoma in mind while dealing with a patient of mycosis fungoides. Our case immunohistochemically supports the distinct etiopathogenesis of Epstein-Barr virus-negative Hodgkin's lymphoma vis-à-vis cutaneous mycosis fungoides.

Investigating potential exogenous tumor initiating and promoting factors for Cutaneous T-Cell Lymphomas (CTCL), a rare skin malignancy.

Most skin malignancies are caused by external and often preventable environmental agents. Multiple reports demonstrated that cutaneous T-cell lymphomas (CTCL) can occur in married couples and cluster in families. Furthermore, recent studies document geographic clustering of this malignancy in Texas as well as in other areas of the United States. Multiple infectious, occupational, and medication causes have been proposed as triggers or promoters of this malignancy including hydrochlorothiazide diuretics, Staphylococcus aureus, dermatophytes, Mycobacterium leprae, Chlamydia pneumoniae, human T-Cell lymphotropic virus type 1 (HTLV1), Epstein-Barr virus (EBV), and herpes simplex virus (HSV). In this report, we review recent evidence evaluating the involvement of these agents in cancer initiation/progression. Most importantly, recent molecular experimental evidence documented for the first time that S. aureus can activate oncogenic STAT3 signaling in malignant T cells. Specifically, S. aureus Enterotoxin type A (SEA) was recently shown to trigger non-malignant infiltrating T cells to release IL-2 and other cytokines. These signals upon binging to their cognate receptors on malignant T cells are then able to activate STAT3 and STAT5 oncogenic signaling and promote cancer progression and IL-17 secretion. In light of these findings, it might be important for patients with exacerbation of their CTCL symptoms to maintain high index of suspicion and treat these individuals for S. aureus colonization and/or sepsis with topical and systemic antibiotics.

Follicular mycosis fungoides - A report of four Indian cases.

BACKGROUND: Follicular Mycosis Fungoides (FMF) is an under-recognized disease in India. Its clinical mimics include Hansen's disease and Sarcoidosis. AIMS: To describe the clinical and pathological features of FMF. MATERIALS AND METHODS: All cases of FMF between January and December 2007 were retrieved. Cases of conventional epidermotropic MF with a minor follicular component were excluded. Slides were reviewed by two observers. The following criteria were assessed: degree and density of folliculotropism of lymphocytes, location of folliculotropism (infundibular / isthmic / bulbar), follicular mucin, eosinophils, granulomas, and conventional epidermotropism. Each feature was assigned a semi-quantitative grade. RESULTS: There were four cases of FMF, with an equal gender distribution and a mean age of 17.5 years. All lesions were on the face. They presented as: hypopigmented patches (2) and erythematous plaques (2). Alopecia was seen in two cases. The clinical diagnosis was Hansen's disease in all four, with a differential of Alopecia mucinosa / Sarcoidosis in two cases.The histological features seen were: disproportionate folliculotropism, lymphocyte tagging with haloes, follicular mucin, and nucleomegaly / convolution in all four cases, prominent eosinophils (2), epithelioid granulomas (1), eccrine infiltration (4), parakeratosis at the follicular ostia (2), and sebaceotropism (1). The infiltrate was bulbar (4) and isthmic (2). The rest of the epidermis showed no hint of conventional MF. CONCLUSION: The preferential features for FMF were involvement of face, dominant folliculotropism, nuclear atypia and convolution, and follicular mucin. Presence of granulomas and eosinophils necessitated exclusion of infectious causes. The absence of findings of MF in the rest of the epidermis should not deter pathologists from rendering this diagnosis.