Background: In 2007, three patients from Impregnated Web Technology (IWT) factory were referred to Groote Schuur occupational clinic with contact dermatitis. The IWT factory manufactures sanding and grinding discs, traditionally a low latex exposure industry. Workers at this factory were introduced to latex gloves in 2004 to protect their hands for various reasons. One of the patient was referred with raised latex specific IgE. Our preliminary diagnosis was irritant contact dermatitis. The dermatitis cleared after avoiding latex gloves. The other two were referred with negative latex specific IgE. One was subsequently diagnosed of fiberglass dermatitis confirmed with histology and the other with urticaria based on the history. Because of the perception that skin problems equate to latex allergy we decided to study the relevance of a positive latex specific IgE in a nonmedical setting. Objective: The objective of this study is to determine the prevalence and relevance of latex sensitization at this traditionally a low latex exposure factory. It also aimed to increase awareness of latex exposure and provide recommendations for preventing and managing latex allergies. Methods: A cross sectional study of the workers on duty was conducted at the IWT factory over 2 days. There were no exclusion criteria. Ethics approval was obtained. Workers who volunteered were asked to sign informed consent and answer 3 questionnaires. Questioned asked were related to glove use at work and at home. They were also examined by the investigator and had a blood sample taken for total IgE and latex specific IgE measurement. Results: There were 160 workers on the factory floor over the study period. Only 81 workers volunteered giving a response rate of 51 %. The point prevalence of latex sensitization was 16 %(13/81). There was a significant relationship between workers who had skin signs and wore glove, however there was no association between glove usage and total and latex specific IgE. A raised latex specific IgE was associated with permanent employment. Conclusion: The prevalence of elevated latex specific IgE amongst workers at IWT factory was high, in the range of that reported of medical personnel, suggesting a source of latex exposure in the work place. The reasons for glove use amongst the workers revealed an appropriate use of natural rubber latex gloves with unnecessary latex exposure. Although we could not link the high prevalence of latex specific IgE to the use of gloves, subgroup analysis with larger numbers of workers may expose an association suggested by a higher prevalence in permanent workers. We suggest the use of more appropriate gloves selected for the protection needed. A latex specific IgE test should be performed only for workers with strong suspicion of latex sensitization, not simply skin signs and symptoms.

Human herpes virus 8 (HHV8) is the aetiological agent of all forms of Kaposi's sarcoma (KS). Seven major subtypes (A, B, C, D, E, F, Z) based on genetic variability of open reading frame (ORF)-K1, have been identified. Numerous studies point to differing tumorigenic and pathogenic properties of the HHV8 subtypes. The study objective was to determine the prevalence of the HHV8 subtypes in a cohort of clinical and histologically confirmed KS in Cape Town, South Africa, and analyse associations between the different subtypes, clinico- epidemiological forms and clinical presentation of KS. The clinical data was prospectively collected and recorded on a body diagram and with photographs. Demographic data was retrospectively collected from clinical records. Tissue biopsies were taken for ORF-K1 subtyping. Out of a cohort of 103, eighty six patients were subtyped; 81 AIDS (aquired immune deficiency syndrome)-KS and 5 African endemic. Subtype A5 (42/86) and B2 (16/86) predominated. B1, B3, A1 and A4 subtypes were identified in 10/86, 9/86, 4/86 and 1/86 patients respectively. A5, B1, B2 and B3 were found in African blacks and individuals of mixed ancestry, while subtypes A1 and A4 are found only in whites and individuals of mixed ancestry. Subtype A5 was associated with >10 KS lesions at presentation in the AIDS-cohort (32/38, p=0,050), but not in the African endemic patients (2/4, p=0,600). Subtypes A1 and A4 were less likely to be associated with poor risk tumour extension (p=0,031) and A1 was associated with lower likelihood of lower limb involvement (p=0,004).

Background: Bleeding from the popular clean-shave ‘chiskop’ haircut was recently reported as prevalent in South Africa (SA), a country with 6.9 million HIV-infected people. Objectives. To investigate the prevalence of barber hair clipper contamination with blood and HIV and hepatitis B viruses. Methods: Fifty barbers from three townships in Cape Town, SA, were invited to participate. One clipper from each barber was collected immediately after it had been used for a cleanshave haircut. Each clipper was rinsed with phosphate-buffered saline and then submerged in viral medium. The polymerase chain reaction (PCR) was used to identify the bloodspecific RNA marker haemoglobin beta (HBB), hepatitis B virus (HBV) and HIV. Results: The clean-shave haircut was the most common haircut requested by clients (78%). Of the clippers collected, 42% were positive for HBB, confirming detection of blood, none were positive for HIV, and 4 (8%) were positive for HBV. Two clippers (clippers 16 and 20) were positive on qualitative HBV PCR. HBV DNA from clipper 16 clustered with genotype A sequences from SA, India, Brazil and Martinique, while clipper 20 clustered with SA genotype D sequences. The clipper 20 sequence was identical to a subtype D sequence (GenBank accession AY233291) from Gauteng, SA. Conclusion: This study confirms that there is significant contamination of barber hair clippers with blood and blood-borne viruses. Hepatitis B was detected with enough DNA copies to pose a risk of transmitting infection. Although HIV was not detected in this small study, the risk of transmission should be quantified. Further studies to investigate barber clipper sterilization practices and whether the clean-shave hairstyle is an independent risk factor for HIV, HBV and hepatitis C virus infections are warranted. Public education on individual clipper ownership (as is the case with a toothbrush) should be advocated for clean-shave and blade-fade haircuts.

Systemic lupus erythematosus, considered a multifactorial autoimmune disease, is a disease affecting many systems, with associated immunological abnormalities. It has a striking diversity of clinical patterns, pathologies and prognoses. Genetic factors determine the inherited baseline, on which environmental, hormonal and infectious triggers act to produce autoantibodies. Ro antibodies have been considered pathogenic in subacute cutaneous and neonatal lupus erythematosus. I affinity-purified antibodies to the 52 kD Ro from immunised rabbits (whole 52 kD protein) and human sera (using two immunodominant regions of the protein). I affinity-purified antibodies to the 60 kD Ro from immunised rabbits (whole 60 kD protein) and human sera (using two immunodominant regions of the protein, as well as the total "native" protein). Using these purified antibodies, with immunofluorescence on normal neonatal human keratinocytes, I showed that the 52 kD Ro is mainly cytoplasmic and the 60 kD Ro is mostly nuclear, with some fine cytoplasmic staining. I looked at the capacity of these purified antibodies to penetrate living keratinocytes under various conditions (hormones, drugs and vitamins). No antibody penetration was found, although one whole serum gave low levels of intracellular fluorescence. I studied the putative membrane translocation of 52 kD and 60 kD Ro under conditions of stress (UV A or UVB with or without hormones, drugs, vitamins and heat shock). I could not identify translocation of the 52 or 60 kD antigens with purified antibodies, although some whole sera showed fluorescence. I can find no evidence that antibodies directed against the 52 and 60 kD Ro antigens cause cutaneous disease.

Background: Excessive sun exposure and high human immunodeficiency virus prevalence increase skin cancer risk in South Africa. Objective: To describe the nature and extent of skin cancers presenting in public and private health sectors of the Northern Cape Province. Methods: A retrospective analysis of histologically-confirmed new primary cutaneous malignancies from 1/1/2008 to 31/12/2012 was conducted using public and private health sector databases. Types, quantity and distribution of common invasive malignancies by population group, age, gender, anatomical site and health sector were explored. One-year cumulative incidence was calculated and logistic regression models were used to analyse incidence and melanoma thickness trends. Results: 4270 biopsies (14 cutaneous malignancies) were identified. Most common were Squamous Cell Carcinoma (SCC), Basal Cell Carcinoma (BCC), Kaposi Sarcoma (KS), Cutaneous Malignant Melanoma (CMM) and Basosquamous carcinoma. The odds of a White male developing SCC increased by 8% each year (OR: 1.08; CI: 1.01-1.15; p-value: 0.022) whilst the odds of a Black male developing SCC and KS decreased by 9% (OR: 0.91; CI: 0.84-0.99; p-value: 0.033) and 18% (OR: 0.82; CI: 0.70-0.97; p-value: 0.022) each year, respectively. SCC and CMM were diagnosed at more advanced stages within public versus private sectors. CMM is being detected earlier, as indicated by low stage depth increasing by 72% annually (OR: 1.72; 95% CI: 1.04-3.01; p-value: 0.042). Conclusion: Results suggest that reported skin cancer patterns are changing. There is a need for further research and equitable appropriation of financial resources and effort toward developing primary skin cancer prevention initiatives in South Africa.

BACKGROUND The pathogenesis of alopecia areata (AA) is poorly understood and multifactorial. There seems to be a strong belief, but conflicting evidence that stress causes or exacerbates AA. Hair cortisol measurement has been proven to be a reliable biological marker for cumulative prior stress. This measurement has up to date not been used in AA cases and may provide convincing evidence in the debate of stress and AA. OBJECTIVES: The primary aim of this project was to determine whether stress triggers onset of hair loss (OOHL) in AA by analysing the relationship between hair cortisol concentrations (HCCs) pre-OOHL in cases vs controls. Three secondary objectives were identified: • To determine whether there is a difference in HCC of lesional skin versus perilesional skin in cases. • To determine whether there is a correlation between disease activity (as determined by the hair pull test) and HCC. • To determine whether validated stress questionnaires correlate with HCC. METHODS A case control study was performed. Fourteen patients, fulfilling the inclusion criteria were recruited from the GSH and RXH outpatient departments. For each case consent was obtained, a data sheet was filled out, stress questionnaire(s) and two strands of hair, one lesional and one peri-lesional, were collected. Next, 14 healthy controls were recruited from whom a hair strand each was collected. On the hair samples, the position of onset of hair loss (OOHL) was determined by measuring one centimetre per month after OOHL, from the proximal (scalp near) end. Then three sections of three centimetres each were cut, two distally (representing the six-month period before OOHL) and one proximally (representing the three months post OOHL). In six of these cases a fourth or “current” section was obtained. This represented the section on the scalp and thus reflected current stress by measuring the most recent HCC. Next, the HCC’s of these sections were measured using the Salivary ELISA Cortisol kit©. An additional 44 cases, not meeting the inclusion criteria, were recruited for acquisition of additional stress questionnaires and data sheets. RESULTS HCC’s on average were higher in cases than in controls (before, during and after OOHL). The difference in HCC’s, however, was not statistically significant. There was no statistical difference between HCC’s in lesional and peri-lesional scalp samples. Distal section HCC’s were the highest. HCC’s correlated positively with disease activity, but was nonsignificant. There was no statistically significant relationship between HCC’s and stress questionnaires. CONCLUSIONS: Although the result was not statistically significant, likely due to small sample size, stress as measured by HCC may trigger OOHL in AA. HCC does not play a role in whether an area of the scalp is affected or not. Disease activity may be cause for stress. A larger study is warranted to validate these findings.

Background: Folliculitis keloidalis nuchae (FKN) is a chronic inflammatory condition that targets the hair follicle, leading to keloidal scarring and alopecia. The absence of a severity scoring tool for FKN limits objective assessment of disease progression and response to treatment. Objectives: To develop and test the reliability of a severity scoring tool for FKN. Methods: The tool was developed based on lesion type, number, size and distribution on the scalp. An initial pilot period with 2 assessors was followed by the main study that used 78 anonymised and standardised clinical photographs of the back of the scalp. The participants were selected from an ongoing case control study of FKN. The assessors could allocate disease severity in one of 14 categories (with/without inflammation). However, inflammation (especially erythema) can be missed in photographs of pigmented skin. Thus, two groups of analysis were conducted first with all 14 and again with 8 categories (i.e. excluding inflammation). Assessors were 4 dermatology consultants and 7 registrars, who all independently scored the same anonymised and standardised photographs on two separate occasions, 2 weeks apart. Results: Inter-observer standard errors were higher with the 14-category compared to the 8- category analysis for both consultants and registrars. The intraclass correlation coefficient for registrars improved from poor [0.46 (0.36 -0.56)] to good [0.74 (0.68- 0.80)] with 14 compared to 8-categories, but stayed the same for consultants [0.82 (0.76 – 0.88) versus 0.81 (0.75 – 0.87)]. Limitations of the study were the use of clinical photographs instead of live participants and the problem that the signs of inflammation may be particularly difficult to judge in pigmented skin. Conclusion: We developed a severity scoring tool with poor to good reliability which also highlighted the difficulty of perceiving inflammation from clinical photographs. This improved with the seniority of the observer. The 8-category analysis has good reliability for clinical photographs for both junior and senior staff. For live patient care and clinical trials the 14-category version is likely to be more useful, but requires validation.

Background: Autoimmune bullous dermatoses present with overlapping clinical features that require histopathological correlation. Immunofluorescence is the most routinely used reliable investigation for diagnosis but requires specialised equipment and is technically sophisticated. Collagen IV immunohistochemistry is reported as a reliable test for the diagnosis of epidermolysis bullosa acquisita whereby It stains the roof of a subepidermal blister and would be expected on the floor in bullous pemphigoid. This technique could be performed as an easily accessible alternative to direct immunofluorescence and has been used anecdotally at our hospital. Aim: To investigate whether collagen IV immunohistochemistry can be used as a reliable histopathological confirmation of bullous pemphigoid. Methods: Two major investigations: 1. A systematic literature search was undertaken of all studies describing the use of collagen IV immunohistochemistry and those comparing it with immunofluorescence in the diagnosis of bullous pemphigoid. 2. A retrospective study of patients diagnosed with bullous pemphigoid over 12 years seen at Groote Schuur Hospital was performed. Patient records that had results for both direct immunofluorescence and collagen IV immunohistochemistry were selected. The positive percentage agreement was calculated. Results: 1. Two studies were found that investigated the use of collagen IV immunohistochemistry in bullous pemphigoid. All reported 33 (100%) cases demonstrated collagen IV at the floor of a subepidermal blister. Of these, 25/25 cases were in agreement with direct immunofluorescence and 7/8 with indirect immunofluorescence which were used as reference standard investigations. 2. In this study, collagen IV was positive in 96% (79/82) of cases and direct immunofluorescence was positive in 85% (72/82) of cases. A positive percentage agreement of 80.5% suggested a strongly positive test accordance. Limitations: 1. The literature search was limited to articles written in english only. 2. The retrospective design and the lack of controls without bullous pemphigoid made it impossible to calculate sensitivity and specificity as well as the kappa statistic. Conclusion: Collagen IV immunohistochemistry is a valid, simple and widely available test which demonstrates accordance with routinely used direct immunofluorescence in the confirmation of bullous pemphigoid. Through clinical and histomorphological correlation, it may be a useful test in resourcelimited settings without facilities for direct immunofluorescence. However, larger controlled studies are warranted to confirm this.

Introduction: All first-line anti-tuberculosis drugs can be associated with all phenotypes of cutaneous adverse drug reactions (CADR). Second-line drugs are associated with much poorer outcomes. Thus, identifying the offending drug in poly-pharmacy is difficult. Re -challenge with the drug is the gold standard in identifying the offender, however poses unacceptably high risk of CADR recurrence. Population and drug-specific genomics help identify those susceptible to adverse reactions to a drug facilitating avoidance of the drug. Objective: To investigate the genomic susceptibility in patients with confirmed rifampicin and or isoniazid-associated hypersensitivity reactions using both genome- wide association studies and candidate gene approaches. Methods: A case control study using 14 patients with previous tuberculosis-associated CADR who were re-challenged with first-line anti-tuberculosis drugs and subsequently developed re-challenge reactions to either isoniazid or rifampicin as cases. These were compared with 30 controls who had tolerated rifampicin and isoniazid during the re- challenge process (12 patients, Group 1a) and consecutive patients who had been on TB treatment for at least 12 weeks without developing any adverse drug reaction (1 8 patients, Group 1b) and 200 black South Africans from the general population. HLA genotypes of the samples were determined by SeCore® HLA Sequence based typing (Invitrogen, Life technologies, USA), and potential ambiguities were resolved by sequencing-based typing. Results: We found HLA-B*58:02 (OR=3.6; 95% CI: 1.4-8.99) and HLA-DRB1*09:01 (OR=15.3; 95% CI: 2.1-113.1) to be significantly more prevalent in patients who developed rifampicin and isoniazid-associated CADR as compared to black South African general population. However, we found no significant associations between HLA genotype and rifampicin/isoniazid-associated CADR when we compared the cases to our study controls that had tolerated rifampicin and isoniazid. HLA-B *58.02 was not found to be statistically associated with HIV positive status (p=0.42) and DRESS phenotype ( p= 0.6279). The majority of our cases were black Africans. Approximately 80% of our cases and controls were HIV-infected. DRESS/DIHS was the prevalent phenotype of CADR, accounting for approximately 80% of cases and controls. Discussion: To our knowledge, this is the first study to show an association between HLA-B*58:02 and HLA-DRB1*09:01 alleles and severe cutaneous adverse drugs reactions secondary to rifampicin and isoniazid in an African population. We identify 2 candidate HLA alleles that need confirmation of their association in African patients who develop rifampicin or isoniazid-associated CADR in larger studies. The value of identifying candidate alleles could lead to CADR preventative screening prior to initiating anti-tuberculosis therapy in black South Africans. The HLA-B*58:02 noted in our cases and controls tolerant of the drugs might not be associated with CADR but could be a reflection of the HIV status and control in HIV-TB co-infected persons. Conclusion: HLA-B*58:02 and HLA-DRB1*09:01 may be associated with rifampicin and isoniazid-associated CADR. Alternately HLA-B*58:02 may be associated with HIV status rather than CADR. A sufficiently powered study is needed to confirm this association.

Background: Over the past decade there has been a worldwide increase in the number of minimally invasive cosmetic procedures, such as dermal fillers. As there are few studies in this field, with most focussing on cosmetic surgery, we conducted research into perceptions around use of dermal fillers, which could contribute to standards of care in administering minimally invasive aesthetic procedures. Objectives: 1. To determine the motivational factors and perceived benefits in people who have had dermal fillers. 2. To assess the need for pre- and post-procedure counselling Methods: We conducted in depth semi-structured patient interviews in people who had had dermal fillers. All 6 participants were adult women. A qualitative comparative approach was used to analyse interview scripts, generating categories and subcategories. Data was further analysed using the theory of planned behaviour. Results: Motivational factors were classified as follows: pressure from immediate social circle, occupational exposure, societal pressure, perceived benefits, and influence of media. Participants supported counselling, to establish motivational factors, screen for psychiatric disorders, gain informed consent and obtain post-procedure feedback. Limitations: Sampling was from a single dermatology practice. Participants were mostly middle-aged, White women from a high-income group. As volunteers chose to participate there may have been selection bias. Our findings may therefore have limited generalisability. Conclusions: Motivations for dermal fillers were influenced by personal and societal beliefs. The findings emphasize the importance of pre- and post-procedure counselling in cosmetic dermatology. Further qualitative research across a more diverse group might yield additional insights.