Photoletter to the editor: Atypical primary cutaneous mucormycosis of the scalp.

The risk of UV radiation (UVR)-induced non-melanoma skin cancer (NMSC) is dramatically increased in immunosuppressed organ transplant recipients compared to immunocompetent patients. In the skin, p53 up-regulated modulator of apoptosis (PUMA) is a central regulator of apoptosis in response to UVR damage and immune response regulation. Data on the expression of PUMA in patients with NMSC relative to immune status is limited To study differences in the expression and distribution of PUMA in cutaneous SCC and BCC by immunohistochemistry between immunocompetent patients and organ transplant recipients, and the effect of CsA-containing immunosuppressive maintenance regimens on this expression. PUMA expression in SCC (n = 34) and BCC (n = 20) was analysed comparatively by immunohistochemical staining in matched cohorts of 27 immunocompetent patients and 27 organ transplant recipients SCC and BCC showed unequivocal positive PUMA expression, however, there was no significant difference in NMSC between organ transplant recipients and immunocompetent patients. A 17% reduction in staining score for PUMA in SCC, but not in BCC, of organ transplant recipients treated with a cyclosporin (CsA)-containing regimen was noted compared to organ transplant recipients without chronic CsA intake (p = 0.0381) PUMA expression in SCC, but not BCC, is significantly reduced by CsA-containing therapy, suggesting a disturbance of apoptosis by iatrogenic immunosuppression with a divergent impact on SCC and BCC.

Chronic immunosuppression in organ transplant recipients (OTRs) is associated with a significantly elevated risk of cutaneous malignancies, particularly squamous cell carcinoma (SCC). Skin cancer prevention should therefore be encouraged for all OTRs and requires patient education, as well as a collaborative effort between dermatologists and transplant teams. This chapter discusses both primary and secondary measures for skin cancer prevention. All OTRs should be counselled regarding photoprotection and sun safety, including the correct use of sunscreen and sun-protective clothing. Chemoprevention with acitretin has been shown to be beneficial in OTRs with a history of multiple SCCs. Nicotinamide is a promising chemoprophylaxis agent but larger trials are required to determine its efficacy in OTRs. Field-based therapy, such as photodynamic therapy and topical 5% fluorouracil, should be considered in patients with multiple actinic keratoses. As the type of immunosuppressive agent appears to correlate with varying risks of keratinocyte cancer development, revision of immunosuppression can be a useful neoadjuvant/adjuvant approach in preventing skin cancers in high-risk OTRs.

Skin Cancers in Organ Transplant Recipients.

Genomic characterization of a novel human papillomavirus (HPV-117) with a high viral load in a persisting wart

Treatment-related immunosuppression in organ transplant recipients has been linked to increased incidence and risk of progression for several malignancies. Using a population-based cancer cohort, we evaluated whether organ transplantation was associated with worse prognosis in elderly patients with non-small cell lung cancer (NSCLC). Using the Surveillance, Epidemiology, and End Results Registry linked to Medicare claims, we identified 597 patients aged 65 years or older with NSCLC who had received organ transplants (kidney, liver, heart, or lung) before cancer diagnosis. These cases were compared to 114,410 untransplanted NSCLC patients. We compared overall survival (OS) by transplant status using Kaplan-Meier methods and Cox regression. To account for an increased risk of non-lung cancer death (competing risks) in transplant recipients, we used conditional probability function (CPF) analyses. Multiple CPF regression was used to evaluate lung cancer prognosis in organ transplant recipients while adjusting for confounders. Transplant recipients presented with earlier stage lung cancer (P = 0.002) and were more likely to have squamous cell carcinoma (P = 0.02). Cox regression analyses showed that having received a non-lung organ transplant was associated with poorer OS (P < 0.05), whereas lung transplantation was associated with no difference in prognosis. After accounting for competing risks of death using CPF regression, no differences in cancer-specific survival were noted between non-lung transplant recipients and nontransplant patients. Non-lung solid organ transplant recipients who developed NSCLC had worse OS than nontransplant recipients due to competing risks of death. Lung cancer-specific survival analyses suggest that NSCLC tumor behavior may be similar in these 2 groups.

Over the past several decades, there has been increasing interest in understanding the roles of the immune system in the development and progression of cancer. The importance of the immune system in human skin cancer has been long recognized based primarily upon the increased incidence of skin cancers in organ transplant recipients and mechanisms of ultraviolet (UV) radiation-mediated immunomodulation. In this review, we integrate multiple lines of evidence highlighting the roles of the immune system in skin cancer. First, we discuss the concepts of cancer immunosurveillance and immunoediting as they might relate to human skin cancers. We then describe the clinical and molecular mechanisms of skin cancer development and progression in the contexts of therapeutic immunosuppression in organ transplant recipients, viral oncogenesis, and UV radiation-induced immunomodulation with a primary focus on basal cell carcinoma and squamous cell carcinoma. The clinical evidence supporting expanding roles for immunotherapy is also described. Finally, we discuss recent research examining the functions of particular immune cell subsets in skin cancer and how they might contribute to both antitumour and protumour effects. A better understanding of the biological mechanisms of cancer immunosurveillance holds the promise of enabling better therapies.

A broad spectrum of human papillomaviruses (HPV) has been detected in warts from immunocompetent patients and a much more diverse range from immunosuppressed organ transplant recipients (OTR). To determine the HPV types in warts from OTR, we assessed present infections of mucosal (alpha-PV), wart-associated (alpha-, micro- and nu-PV) and cutaneous HPV types (beta-/gamma-PV) in immunocompetent patients and OTR. Patients/methods Forty-one warts from 29 immunocompetent patients (non-OTR) and 53 warts from 33 OTR were analysed for DNA of human alpha-, beta-, gamma-, micro- and nu-PV. For frequent types viral load was determined by quantitative real-time PCR. Compared with non-OTR prevalence of cutaneous HPV (79% vs. 49%, P < 0.01) and the number of multiple infections (62% vs. 17%, P < 0.0001) were significantly increased. The mean viral load of the wart-associated HPV was more than 10(5)-fold higher compared with human beta-PV in both cohorts. The high load of wart-associated HPV suggests an active role of these viruses rather than cutaneous types in warts independent of immunosuppression; however, the substantial fraction of warts with low HPV genome copies remains to be explained.

Tumor Lysis Syndrome Associated With Reduced Immunosuppression in a Lung Transplant Recipient

Fungal infections

Pain and inferior efficacy are major limiting factors of conventional photodynamic therapy for the field treatment of actinic keratoses in immunosuppressed organ transplant recipients. This prospective randomized controlled study evaluates the efficacy and tolerability of ablative fractional laser system pretreatment combined with low-irradiance photodynamic therapy (18.5 mW/cm2) compared with conventional photodynamic therapy (61.67 mW/cm2) in the treatment of actinic keratoses on the face and scalp in organ transplant recipients, using a red light-emitting diode lamp at a total light dose of 37 J/cm2. Low-irradiance photodynamic therapy combined with Er:YAG pretreatment achieved a significantly superior lesion response rate (mean ± standard deviation 77.3 ± 23.6%) compared with conventional photodynamic therapy (61.8 ± 21.4%; p = 0.025) in intra-individual fields at 3 months without negatively impacting pain (p = 0.777) or cosmetic outcome (p = 0.157).

Cells to Surgery Quiz: December 2018

Emergence of Mucormycosis during COVID-19 Pandemic and Dermatological Manifestations.

Cutaneous carcinogenesis is increased in immunosuppressed organ transplant recipients (OTR). Tumour accrual is a useful measure for the rate of cutaneous carcinogenesis. There are few studies in tumour accrual rates in OTR in Australia. This was a prospective study of renal transplant recipients in a single tertiary referral centre over 5 years (60 months). Outcome measures included tumour accrual, and numbers of skin cancers according to clinical risk factors (age, sex, anatomical location, skin phototype, duration of immunosuppression, history of graft rejection, acitretin use, occupational sun exposure and family history of skin cancer). A total of 142 patients were included in the study, with a median follow-up duration of 1.9 years. Of these patients, 53 (37%) developed a total of 341 invasive non-melanoma skin cancers (NMSC) (253 squamous cell carcinoma [SCC] and 88 basal cell carcinoma [BCC]) over the study period. Accrual for SCC and BCC were 0.89 SCC/patient per year and 0.31 BCC/patient per year, respectively. The overall NMSC accrual was 1.20 NMSC/patient per year. SCC accrual increased with the duration of immunosuppression. NMSC accrual increased with a history of graft rejection. The current study provides prospective, histologically verified and quantitative evidence for the increase of cutaneous carcinogenesis in renal transplant recipients in Victoria, Australia.

Inflammatory dermatoses and inflammatory reaction patterns to underlying systemic disease are relatively uncommon in immunosuppressed organ transplant recipients (OTRs) and infection should always be suspected as a possible cause. We present an OTR with biopsy-proven panniculitis resulting from disseminated toxoplasmosis, only identified after extensive histological analysis. A 45-year-old Nigerian woman who was profoundly immunocompromised through a combination of a kidney transplant 12 months earlier, hyposplenism due to sickle cell anaemia and a CD4+ count 74 × 106 cells L–1 (&amp;gt; 455 × 106 L–1) presented with a 3-month history of &amp;gt; 20 painful, red–purple and hyperpigmented subcutaneous nodules and plaques up to 2 cm in diameter limited to her legs, associated with fatigue and weight loss. She only had childhood contact with cats. There was no lymphoedema or lymphadenopathy, and she was HIV negative. Urgent skin biopsy excluded Kaposi sarcoma and demonstrated a lobular, necrotizing panniculitis, a mixed inflammatory cell infiltrate and evidence of vasculitis. The cause was unclear; cultures for mycobacterial, fungal and bacterial infections were negative. However, on rereview of histology, within areas of inflammation and necrosis in the subcutaneous fat, there were a few scattered structures (10–30 μm in diameter) consisting of small basophilic periodic acid–Schiff-positive ‘dots’ within bright eosinophilic cytoplasm, raising the possibility of toxoplasmosis. Toxoplasma immuno­staining was positive. Further tertiary review of histology and immunostaining by the Hospital for Tropical Diseases agreed that there was no other causative organism and the panniculitis and vasculitis were consistent with active toxoplasmosis. The diagnosis of toxoplasma reactivation was supported by positive toxoplasma IgG on pretransplant bloods. Magnetic resonance imaging of the head was consistent with cerebral toxoplasmosis. She received treatment with clindamycin, pyrimethamine and folinic acid and, thereafter, long-term cotrimoxazole prophylaxis. Cutaneous toxoplasmosis is rare, with only three reported cases over the last 10 years. Historically, a wide spectrum of clinical morphologies has been described, including maculopapular rashes, nodules, ulcers, dermatomyositis and even mimicry of varicella and graft-versus-host disease. Most cases affect immunocompromised patients. In our patient, this was the result of reactivation of latent infection, which is more common in West Africa, coinciding with profound immunosuppression. In our case, a diagnosis was only made after extensive histological review. Given the varied morphologies of clinical presentations, it is possible that this condition may be easily missed, with potentially serious consequences. In summary, we highlight the importance of maintaining a high index of suspicion for infection and the need for careful clinicopathological correlation in OTRs presenting with apparently atypical inflammatory skin lesions.

Funding sources: none. Conflicts of interest: none declared. Dear Editor, Ultraviolet (UV)B radiation is a substantial risk factor for skin cancer in both immune‐competent and immunosuppressed organ transplant recipients (OTRs). In OTRs, additional exposure to UVA through drug photosensitization may contribute to their excess risk, which is well established.1 There is some evidence for preferential lateralization of photodamage and (pre)cancers, in the general population, to the side most exposed to UV radiation while driving. Moehrle et al.2 reported that left‐sided drivers receive five times more UV to the left arm than the right arm, and 20 times more UV on the left side of the face than the right. Actinic keratoses have been reported to occur more frequently on the right side of the body in Australian drivers, where drivers sit on the right side of the car. A left‐sided bias in skin cancer was observed in the U.S.A., where drivers sit on the left side of the car.3 4 5