A uniquely distributed purpuric drug eruption from acalabrutinib.

Acalabrutinib is a second-generation, highly selective Bruton's Tyrosine Kinase inhibitor (BTKi) indicated for use in some mature B-cell malignancies. The authors describe a uniquely distributed drug reaction presenting as palpable purpura over the bilateral upper limbs. BTKi is theorised to cause haemorrhage through off-target inhibition of Tec kinases and EGFR receptors. Dermatologists play an integral role in the multidisciplinary management of these patients to limit the negative impact on patient quality of life and, more importantly, to restrict dose reduction or treatment discontinuation.

Reflectance confocal microscopy role in mycosis fungoides follow-up.

BACKGROUND: Reflectance confocal microscopy (RCM) is a useful tool for many skin cancers, allowing non-invasive evaluation over time and identifying areas of active disease. Its role to follow-up mycosis fungoides (MF) patients has not yet been evaluated. OBJECTIVE: To assess the level of agreement between RCM and histopathology and to develop a RCM checklist that could help monitoring MF patients. METHOD: Prospective study in a cutaneous lymphoma clinic of a tertiary hospital in Australia. RCM and biopsies were performed on the same area at baseline, before commencing or changing treatment, and at 6 months after starting treatment. Normal skin sites were also analysed and acted as controls. RCM features and histopathological findings were blindly evaluated by the confocalist and pathologist. Correlation between RCM and histology was measured by overall per cent of agreement (OPA), kappa and ROC curves. Additionally, RCM images before and after treatment were assessed blinded from clinical information and correlated to clinical assessment. RESULTS: Thirty-eight MF lesions were included. Nineteen of these 38 were re-assessed by RCM 6 months later. Fifty biopsies were performed (38 at baseline and 12 after 6 months). The combination of four RCM features corresponding to Pautrier's microabscess, epidermal and junctional lymphocytes and interface dermatitis formed the RCM checklist for MF that predicted the severity of disease with AUC of 0.95 (P = .003). CONCLUSION: Reflectance confocal microscopy can assess activity within a lesion and over time and assist in the clinical management of patients with MF.

Mycosis fungoides and Sézary syndrome: Australian clinical practice statement.

Primary cutaneous lymphomas represent a heterogeneous group of T- and B-cell lymphomas with distinct clinical presentations, histopathologic features, treatment approaches and outcomes. The cutaneous T-cell lymphomas, which include mycosis fungoides and Sézary syndrome, account for the majority of the cutaneous lymphomas. This Clinical Practice Statement is reflective of the current clinical practice in Australia. An expanded form of the Clinical Practice Statement (and updates), along with helpful patient resources and access to support groups, can be found at the following (http://www.australasianlymphomaalliance.org.au).

Systematic review and proposal of an in vivo reflectance confocal microscopy assessment tool for cutaneous lymphoma.

BACKGROUND: Reflectance confocal microscopy (RCM) is a non-invasive imaging technique that provides dynamic information and allows in vivo monitoring, with excellent histologic correlation. In the last decade, the use of RCM for cutaneous T-cell lymphomas (CTCL) has been reported. CTCL may require multiple biopsies for diagnosis due to its equivocal clinical presentation. RCM was described as a possible tool to help determine the best site for skin biopsy. This study aims to systematically review all RCM features reported in literature for CTCL. METHOD: A systematic literature search concerning CTCL evaluated by RCM was performed in eight electronic databases until May 2019 following PRISMA-DTA quality assessment. RESULTS: Eighteen RCM features were described in patients with CTCL. The most frequent were: interface dermatitis (89%), epidermal lymphocytes (82%), epidermal architectural disarray (81%), and vesicle-like structure (Pautrier microabscess) (51%). CONCLUSION: In order to establish comparable parameters among the studies identified, we proposed descriptors for CTCL features and a grading system to quantify them. This will facilitate to define the role of RCM in the diagnosis and monitoring of CTCL patients.

Reflectance confocal microscopy as a new diagnostic tool in transformed mycosis fungoides.

Patients with mycosis fungoides typically experience an indolent disease. In some cases, the disease undergoes a process of large cell transformation which often heralds a more aggressive course with shortened overall survival. In order to rule out large cell transformation, biopsy specimens are often collected from patients with established disease who develop new papules, plaques or tumours. In some cases, multiple biopsies are needed and scar, infection and sampling error can occur. Our aim was to evaluate lesions suggestive of large cell transformation using in vivo reflectance confocal microscopy and to correlate confocal features with histopathologic findings in three patients with biopsy-proven mycosis fungoides who developed new lesions during follow-up. A total of six lesions, two lesions per patient, were examined. Reflectance confocal microscopy demonstrated large bright roundish pleomorphic cells in the epidermis, dermoepidermal junction, dermis and hair follicle in 5 of 6 lesions. The same 5 lesions were confirmed as large cell transformation by histopathology. Dermoepidermal junction obscuration, Pautrier microabscesses, epidermal disarray, spongiosis and dendritic cells were also detected by reflectance confocal microscopy and correlated to histopathology. In conclusion, reflectance confocal microscopy is useful in identifying large cell transformation within mycosis fungoides lesions. Reflectance confocal microscopy can therefore be of value in targeting the biopsy site, thereby reducing the chance of a false-negative histopathological finding.

Management of cutaneous T-cell lymphomas: Established and emergent therapies.

Cutaneous T-cell lymphoma is an uncommon group of non-Hodgkin's lymphoma primarily affecting the skin. It is comprised of a variety of entities with different clinical behaviours and prognosis. Mycosis fungoides is the commonest subtype, and Sézary syndrome is a much rarer form of cutaneous T-cell lymphoma. At this stage, control rather than cure is the goal of therapy, with particular emphasis placed on preserving quality of life. Our review of the efficacy, safety profile and accessibility of treatment modalities for mycosis fungoides/Sézary syndrome is a tailored guide for the clinician treating these rare conditions.

Gemcitabine and vinorelbine treatment in cutaneous T-cell lymphoma in four patients.

Treatment options for advanced stage cutaneous T-cell lymphoma (CTCL) are limited by the their efficacy and side-effects profile. Gemcitabine, a pyrimidine analogue, has been reported to be efficacious in CTCL. Most of the studies published used gemcitabine as a single agent in treating advanced CTCL. Our small case series demonstrated that a combination of gemcitabine and vinorelbine induced partial remission in all four patients with refractory or advanced CTCL, although the effects were not sustained for a long duration (2-6 months). Two patients had neutropenia and one had acute hepatitis, requiring discontinuation of treatment.

Tape stripped stratum corneum samples are suitable for diagnosis and comprehensive proteomic investigation in mycosis fungoides.

BACKGROUND: Mycosis Fungoides (MF) is a common cutaneous T-cell lymphoma. It can sometimes be challenging to diagnose MF using current clinico-histopathological criteria. Non-invasive molecular profiling analysis has the potential to aid the diagnosis and understanding of MF. METHOD: Lesional and body site matched normal stratum corneum samples were obtained from the same MF patients (n = 28) using adhesive discs, followed by proteomic analyses using data-independent acquisition mass spectrometry (DIA-MS). Differential abundance analyses and bioinformatic analyses were performed to identify differentially abundant proteins and altered biofunctions between the MF and normal stratum corneum samples. RESULTS: In total, 1303 proteins were identified, of which 290 proteins were significantly changed in the MF cohort compared to the normal stratum corneum. Ingenuity pathway analysis (IPA) predicted the significant inhibition of cell death of cancer cells and significant activation of immune-related activities and viral infection in the MF lesions. MF lesions were also associated with upstream regulators relating to immuno-oncologic dysfunctions. The top-250 variating proteins efficiently separated normal stratum corneum from matched MF samples. CONCLUSION: Non-invasive proteomic analysis could transform the diagnosis of MF by reducing the need for invasive biopsy. The identification of altered biological functions may serve as useful biomarkers to predict MF progression.

The efficacy and safety of methotrexate versus interferon in cutaneous T-cell lymphomas.

OBJECTIVES: Methotrexate (MTX) and interferon (IFN) have been used in the treatment of cutaneous T-cell lymphomas (CTCL) of various subtypes. We review our experience of MTX and IFN use in our patients with CTCL at a tertiary hospital. MATERIALS AND METHODS: Medical records of patients over 4 years were reviewed. We describe the dosages, time to response, response rates, side effects, progression rate, and reasons for discontinuation. RESULTS: Response rate was significantly higher in the IFN group than MTX group (86.67% and 47.4% respectively, p = .01). Disease progression occurred 57.89% in the MTX group whilst only 26.67% progressed with IFN therapy. Patients taking IFN therapy experienced proportionally more side effects of any type than those undertaking MTX treatment (86.67% vs. 47.37%, odds ratio 7.22). However, discontinuation rate in the IFN group (26.67%) was much lower than in the MTX arm (89.47%). CONCLUSIONS: The most significant finding of this study was that patients with CTCL treated with IFN had a better response rate and significantly shorter response time compared with those treated with MTX. Additionally, patients had less disease progression on IFN than with MTX regardless of subtype of T-cell lymphoma and stage of disease.

Abdominal wall ulceration and mucinosis secondary to recombinant human interferon-beta-1b.

46-year-old woman developed painful ulcers over her lower abdomen in the form of reticulate erythema after injecting interferon beta-1b subcutaneously for multiple sclerosis. Skin biopsy revealed multiple superficial thrombosed vessels with focal epidermal necrosis as well as prominent interstitial mucinosis. Treatment with low-molecular-weight heparin followed by a heparinoid resulted in slow healing of the ulcers but also allowed the subcutaneous interferon injections to be continued.

Case of recalcitrant necrobiotic xanthogranuloma.

A 53-year-old woman with necrobiotic xanthogranuloma presented as infiltrated eyelid plaques, with later development of arm and thigh lesions. Clinical features, including association with immunoglobulin G-kappa paraprotein, and pathological findings were typical of this disorder. Treatment for 15 months with varying combinations of prednisone and multiple chemotherapeutic agents (melphalan, cyclophosphamide and chlorambucil) has led to minimal or no improvement in the clinical lesions or paraprotein. The case demonstrates some of the difficulties in managing this unusual disorder.

Unusual case of subcutaneous panniculitis-like T-cell lymphoma.

An unusual case of subcutaneous panniculitis-like T-cell lymphoma is presented involving multiple organ systems, which eventually culminated in rapid demise from the haemophagocytic syndrome, after an initial protracted course. A 44-year-old man presented in April 2001 with bronchiolitis obliterans organising pneumonia that initially responded well to corticosteroids. However, the condition relapsed on attempted prednisone withdrawal in January 2002 and the patient was noted to have developed truncal subcutaneous nodules. Initial skin biopsy revealed lobular panniculitis, with negative microbiological culture. In July 2002, mononeuritis multiplex was diagnosed after the patient presented with paresthesiae and was treated with pulse cyclophosphamide therapy. By November 2002 there was ulceration of the subcutaneous nodules. Repeat skin biopsy revealed subcutaneous panniculitis-like T-cell lymphoma. The clinical manifestations were supportive of an unifying diagnosis of malignancy involving pulmonary, cutaneous and nervous systems. Combination chemotherapy with fludarabine, mitoxantrone and dexamethasone was commenced. However, the patient deteriorated, with fevers, weight loss, pancytopenia and laboratory features consistent with the haemophagocytic syndrome. Despite maximal supportive therapy the patient succumbed to his disease.