Declining incidence of keratinocyte carcinoma in organ transplant recipients.

BACKGROUND: All organ transplant populations are predisposed to increased rates of keratinocyte carcinoma (KC). Since this increased risk was first appreciated, immunosuppressive regimens have changed and organ transplant recipients (OTRs) have been aggressively screened for KC. There is a perception that these measures have impacted on KC incidence but there is a paucity of population-based studies on post-transplant rates of basal cell carcinoma (BCC). OBJECTIVES: To identify trends in incidence rates for KC following solid organ transplantation over the past two decades. METHODS: This nationwide, population-based study included all solid OTRs transplanted between 1994 and 2014. Patient data were matched to national cancer registry data to determine the standardized incidence ratio (SIR) of KC in solid OTRs compared with the general population. RESULTS: In total 3580 solid OTRs were included. The total follow-up time was 28 407 person-years (median follow-up 7·11 years). The overall SIRs for squamous cell carcinoma (SCC) and BCC were 19·7 and 7·0, respectively. Our study documents a progressive fall in the SIRs for SCC and BCC from peak SIRs (95% confidence intervals) in 1994-1996 of 26·4 (21·5-32·4) and 9·1 (7·4-11·3) to 6·3 (2·3-16·7) and 3·2 (1·4-7·1) in 2012-2014, respectively. The ratio of SCC to BCC has remained at 3 to 1 over the last two decades. CONCLUSIONS: Our study is the first to demonstrate a significant reduction over the past two decades in the incidences of both SCC and BCC following solid organ transplantation. The SCC-to-BCC ratio was maintained, demonstrating that both are reducing equally. This trend coincided with temporal changes in immunosuppressive protocols and the introduction of skin cancer prevention programmes. What's already known about this topic? Prior studies have shown that the risk of cutaneous squamous cell carcinoma (SCC) has declined over recent decades following solid organ transplantation. It is not known whether the risk of basal cell carcinoma (BCC) has reduced in line with this. What does this study add? Our study documents a progressive fall in the risk of SCC and BCC following solid organ transplantation over the last two decades. The SCC-to-BCC ratio was maintained, demonstrating that both are reducing equally. The trends observed in our study coincided with temporal changes in immunosuppressive protocols and the introduction of cancer prevention programmes, suggesting that these factors have positively impacted on the risk of keratinocyte carcinoma in this cohort.

Spinal dysraphisms in the parturient: implications for perioperative anaesthetic care and labour analgesia.

Anaesthetists may encounter parturients with a spectrum of anatomical and functional abnormalities secondary to spinal dysraphisms, which are among the most common neurodevelopmental anomalies. These range from surgically corrected open dysraphisms to previously undiagnosed closed dysraphisms. Both bony and neural structures may be abnormal. In true bony spina bifida, which occurs in up to 50% of the population, failure of fusion of the vertebral arch is seen and neural structures are normal. Ninety percent of such cases are confined to the sacrum. In open dysraphisms, sensory preservation is variable and may be present even in those with grossly impaired motor function. Both epidural and spinal blockade have been described for labour analgesia and operative anaesthesia in selected cases but higher failure and complication rates are reported. Clinical assessment should be performed on an outpatient basis to assess neurological function, evaluate central nervous system shunts and determine latex allergy status. Magnetic resonance imagining is recommended to clarify anatomical abnormalities and to identify levels at which neuraxial techniques can be performed. Of particular concern when performing neuraxial blockade is the possibility of a low-lying spinal cord or conus medullaris and spinal cord tethering. Previous corrective de-tethering surgery frequently does not result in ascent of the conus and re-tethering may be asymptomatic. Ultrasound is not sufficiently validated at the point of care to reliably detect low-lying cords. Epidurals should be performed at anatomically normal levels but spread of local anaesthetic may be impaired by previous surgery.

Two cases of dermatoses koebnerizing within fields of previous radiotherapy.

We describe two patients with newly diagnosed dermatoses localizing to the radiotherapy field following treatment for breast cancer. Patient 1 was a 53-year-old woman who developed bullous morphoea on her left breast two years after radiotherapy. Patient 2 was a 43-year-old woman who developed urticaria pigmentosa on her right breast eight months after radiotherapy and similar lesions gradually developed beyond the radiotherapy field. Both patients experienced a significant delay in diagnosis due to diagnostic confusion and concern over breast cancer recurrence. Irradiated skin demonstrates gradual and sustained alterations in fibrosis due to the production of long-lived cytokines and chemokines. These changes can induce a koebnerizing response in conditions such as morphoea and urticaria pigmentosa. We explore the mechanisms behind radiotherapy-induced skin changes, and highlight the potential for radiotherapy to exacerbate or unmask underlying dermatoses and systemic disease in the months and years following treatment.

Propranolol for the treatment of infantile haemangiomas: our experience with 44 patients.

Propranolol is an effective, safe treatment for complicated infantile haemangiomas (IH). We evaluated all patients (n = 44) with IH treated with propranolol in our department. Of the 44 patients who were begun on propranolol therapy, 26 patients have completed the treatment to date and all had a good response. The mean duration of treatment was 45.7 weeks. Four patients developed rebound growth of their IH, which responded to the reintroduction of propranolol. Two patients with PHACES (posterior fossa malformations, haemangiomas, arterial anomalies, coarctation of the aorta/cardiac abnormalities, eye anomalies and sternal defects/supraumbilical raphe) syndrome were treated with lower than standard doses, because of concern about possible cerebrovascular compromise. Adverse effects were minor in most patients. Three patients discontinued propranolol because of vomiting, wheeze, and hypoglycaemia, respectively. Our duration of treatment was longer than that of other series, and may be due to our group having higher rates of hypotension, recorded in 27.3% of patients, precluding an increase in propranolol dose. Our experience supports that propranolol is an effective first-line agent for complicated IH.

Cutaneous reactions to adalimumab administration.

Patients receiving antitumour necrosis factor-alpha treatment may develop cutaneous reactions. This human monoclonal antibody is used in the treatment of chronic inflammatory diseases, including arthritis and inflammatory bowel disease. A variety of side effects have been documented ranging from infection and vasculitis through to systemic lupus erythematosus and psoriasis. We report on two arthritic patients treated with adalimumab (Humira, Abbot Laboratories, IL, USA) who developed new onset rashes that resolved with discontinuation of therapy. The frequency of these cutaneous reactions has not been fully established and may benefit from a centralised registry.

Mucor mycosis infection presenting as a non-healing ulcer in an immunocompromised patient.

Mucor mycosis is an uncommon saprophytic opportunistic fungus causing localized cutaneous infection associated with high morbidity and, on dissemination, high mortality. We report the case of an immunocompromised patient with an aggressively progressing, painful non-traumatic ulceration, unresponsive to standard treatment. Deep biopsies for haematoxylin and eosin staining and fungal culture revealed the characteristic broad non-septate irregular hyphae of mucor allowing introduction of the appropriate treatment. Infection with mucor mycosis must be considered in today's medical environment as the number of immunocompromised patients increases.

Comparison of the expression of p53, p21, Bax and the induction of apoptosis between patients with basal cell carcinoma and normal controls in response to ultraviolet irradiation.

AIM: Ultraviolet light (UV) is known to cause DNA damage in the epidermis. The damaged DNA is repaired or deleted by apoptosis to prevent the generation of cancer. It has been suggested that a deficient apoptotic mechanism may predispose individuals to skin cancer. Therefore, the response of normal controls and patients with basal cell carcinoma (BCC) to UV irradiation was investigated. METHODS: The buttock skin from normal volunteers and patients with BCC was irradiated using solar simulated radiation (SSR). SSR mimics the effect of natural sunlight. Skin biopsies were excised and examined for p53, p21, and Bax protein expression and for the induction of apoptosis. RESULTS: At 33 hours after UV irradiation, the induction of apoptosis was significantly higher (p = 0.04) in patients with BCC than in normal volunteers (Mann Whitney test). A trend towards higher p21 expression was found at 33 hours in patients with BCC (mean, 18.69 positive cells/field) than in normal volunteers (mean, 9.89), although this difference was not significant (p = 0.05 positive cells/field). CONCLUSION: These results may imply that patients with BCC have enhanced sensitivity to UV irradiation or that there is some defect in the cell arrest or repair pathways, which results in damaged cells been pushed into apoptosis rather than repair.

The expression of p53, p21, Bax and induction of apoptosis in normal volunteers in response to different doses of ultraviolet radiation.

BACKGROUND: Ultraviolet radiation (UVR) damages keratinocytes. Direct DNA damage may undergo enzymatic repair followed by resumption of the normal cell cycle. Cells may also be eliminated without inflammation by the error-free process of programmed cell death or apoptosis. Necrosis of cells can occur after overwhelming damage. Failure of apoptosis leads to retention of cells with persistent mutations. OBJECTIVES: This study investigates p53-dependent apoptotic responses in normal skin following solar-simulated radiation (SSR). METHODS: Sun-protected buttock skin from normal volunteers with no history or clinical evidence of skin cancer was exposed to graded doses of SSR, 0.5, 1, 2 and 3 times the minimal erythema dose (MED). Biopsies taken at a range of time points (4.5, 9, 24, 33, 48 and 72 h) after UVR, quantified the time course and dose-response of apoptosis and the expression of the relevant proteins, p53, p21waf1/Cip1 and Bax, by single and double labelling techniques. RESULTS: Apoptosis was upregulated in a dose-dependent manner as was the expression of p53, p21waf1/Cip1 and Bax in response to SSR. Following exposure to 3 MEDs it was found that: (i) the maximum number of apoptotic cells occurred at 48 h; (ii) p53 protein expression was upregulated from 4 to 72 h preceding peak p21waf1/Cip1 protein expression (9-48 h) and peak Bax protein expression (33 h). CONCLUSIONS: These results suggest that, following SSR, normal human skin induces apoptosis by the p53, p21waf1/Cip1, Bax pathway in vivo. In addition, induction of apoptosis and expression of p53, p21waf1/Cip1 and Bax occurs in a dose-dependent manner.

Sunscreens and the photodermatoses.

The photodermatoses are defined by their clinical features which result from exposure to ultraviolet radiation or visible light. Accurate diagnosis, which is often complicated, is essential to ensure appropriate treatment and protection from precipitating wavelengths. We review the acquired photodermatoses including polymorphic light eruption, hydroa vacciniforme and chronic actinic dermatitis. The genodermatoses including the DNA repair deficiency and melanin-deficient syndromes are discussed, and the best methods for protection of the cutaneous photodermatoses including relevant sunscreen use are elaborated.

The Laugier-Hunziker syndrome.

Laugier and Hunziker described a syndrome consisting of asymptomatic benign areas of hyperpigmentation affecting the lips, buccal mucosa and, in 50%, the fingernails. We report a 67-year-old woman with the clinical features of Laugier-Hunziker syndrome in association with vulval pigmentation. Histology, immunohistochemistry and electron microscopy from the various areas of pigmentation on the body confirmed the benign nature of the pigmentation. We review potential causes of oral and genital pigmentation, and suggest an expansion of the original syndrome described by Laugier and Hunziker to include more widespread areas of benign hyperpigmentation, which may associated.

Genital melanotic macules: clinical, histologic, immunohistochemical, and ultrastructural features.

BACKGROUND: Genital melanotic macules are poorly recognized lesions, which appear as isolated discrete macules. Their occurrence, usually as new pigmented lesions in adult life, can cause concern because they can mimic early melanoma. OBJECTIVE: Our purpose was to define the clinical, histologic, immunohistochemical, and electronmicroscopic features of genital melanotic macules. METHODS: History and clinical features of 10 patients (5 female, 5 male) were assessed in detail. Histologic findings were reviewed in 5 cases, and immunohistochemistry, with the use of the HMB-45 antibody, in 4 cases and electron microscopy in 3 cases. RESULTS: Clinically the lesions varied in color, tan to dark brown/black, and size (0.5-2 cm). Histologic findings showed increased basal pigmentation without atypical features. HMB45 antibody staining was negative. Electron microscopy showed normal morphology and number of melanocytes but increased melanosomes and dermal melanophages. CONCLUSION: Genital melanotic macules are benign, asymptomatic, discrete areas of hyperpigmentation that occur equally in men and women. Histologic, immunohistochemical, and electronmicroscopic study confirms their benign nature.

Partial lipodystrophy and renal disease.

Partial lipodystrophy is a rare disorder with both autosomal recessive and familial forms. The cutaneous findings, which are often subtle, consist of a gradual loss of subcutaneous fat from the face and upper body. Low levels of C3, occasionally low C5 and the presence of the nephritic factor help to identify these patients. Associated systemic abnormalities include the development of mesangiocapillary glomerulonephritis and an increased incidence of autoimmune diseases. Recognition of this unusual disorder is essential for diagnosis and treatment of underlying potentially life- threatening disease.

Oral pigmentation.

Oral pigmentation may be physiological or pathological in nature. It may represent a localized anomaly of limited significance or the presentation of potentially life-threatening multisystem disease. Evaluation of a patient with oral pigmentation requires a systematic approach with resource to appropriate investigations in certain circumstances. A full history of evolution of the pigmentary changes, as well as inquiring into family history, drug ingestion and systemic symptoms of concurrent disease are clearly important in the assessment. The duration, pattern, hue and distribution of colour changes can provide useful diagnostic clues. Special attention is given to newly appearing lesions, or those that have changed significantly in appearance, and biopsy may be needed to validate the clinical impression. This review should enable the reader to increase their familiarity with the assessment of oral pigmentation, the common causes of oral pigmentary change and the rarer disorders of pigmentation seen in this area. The systemic diseases that may give rise to oral pigmentation are detailed and the early signs of oral melanoma are highlighted, as well as the drugs which may cause pigmentary changes in this area and the different pattern of pigmentation they may induce.

Global and regional detection of induced optic disc change by digitized image analysis.

OBJECTIVE: To evaluate two new strategies for the detection of optic disc change within individual eyes by digitized image analysis. METHODS: Eleven normal optic discs of 11 monkeys were imaged with a digital imaging system (Topcon Imagenet, Topcon Instrument Corporation of America, Paramus, NJ) at two intraocular pressures (10 and 45 mm Hg). To detect global change in the disc, we compared conventional optic disc parameters with a new optic disc parameter: mean position of the disc. To detect regional change, the 95% confidence interval for change was calculated for each data point and mapped for each disc. RESULTS: Posterior deformation of the disc surface was detected in seven of 11 eyes using conventional parameters and in 10 of 11 eyes using mean position of the disc. Regions of posterior deformation were detected by 95% confidence interval for change mapping in all 11 discs as localized areas of confluent, posteriorly displaced points. CONCLUSIONS: Mean position of the disc outperformed conventional measurements in the detection of global optic disc change. Ninety-five percent confidence interval for change mapping may allow individual data point-based focal and regional analysis of the disc.

Intraarticular analgesia following knee arthroscopy.

A randomized, double-blind, controlled study was conducted in patients undergoing elective knee arthroscopy to assess the analgesic effect of intraarticular morphine and bupivacaine, alone and in combination. Patients in group 1 (n = 10) received 5 mg of morphine in 25 mL of saline; patients in group 2 (n = 10) received 25 mL of 0.25% bupivacaine (62.5 mg); patients in group 3 (n = 10) received a combination of 5 mg of morphine and 62.5 mg of bupivacaine in 25 mL dilution; and patients in group 4 (n = 10) received 25 mL of saline. All the drugs were injected intraarticularly. Postoperative pain was assessed using the visual analogue scale at 1, 2, 4, 8, and 24 h after the intraarticular injection. The need for supplemental analgesia was recorded. Results showed that there was no significant difference in the pain scores or analgesic requirements between groups 1 and 3. Patients in groups 1 and 3 had significantly lower pain scores than those in groups 2 and 4. These low pain scores were associated with lower requirements of supplementary analgesics. The patients in group 4 showed the highest pain scores and analgesic requirements. We conclude that intraarticular morphine significantly reduces postoperative pain following knee arthroscopy and that there is no advantage of combining bupivacaine with morphine.