Pyoderma gangrenosum, acne, and suppurative hidradenitis syndrome in end-stage renal disease successfully treated with adalimumab.

PASH syndrome (pyoderma gangrenosum, acne, and suppurative hidradenitis) forms part of the spectrum of autoinflammatory diseases. We report an unusual case of PASH syndrome in a patient with end-stagerenal disease (ESRD) who was successfully treated with the tumor necrosis factor inhibitor, adalimumab. The case underscores the challenges associatedwith the treatment of PASH syndrome as well as the ongoing search to establish a genetic basis for the syndrome. Renal impairment has been reported in association with pyoderma gangrenosum but has notbeen described in PASH syndrome. We believe this to be the first reported case of a patient who developed PASH syndrome in the setting of ESRD.

A Profile and Three-Year Follow-Up of Patients with Basal Cell Carcinoma in the Western Cape, South Africa.

Background: Basal cell carcinoma (BCC) is an important malignancy in sub-Saharan Africa. There is a paucity of data regarding BCC in South Africa. Aims: To describe the clinicopathological features of patients presenting with BCC in a cohort of South African patients. Methods: This retrospective descriptive study reviewed the medical records of 149 patients with BCC who attended the dermatology clinic at Tygerberg Academic Hospital from September 2015 to August 2016. Demographic and clinical data of those patients with histologically proven BCC were retrieved from clinical records. The data included the assessment for BCC recurrence after three years (September 2016-August 2019). Results: Of 390 patients, 155 (39.7%) had histologically confirmed BCCs. Complete medical records were available for 149 of these patients, and most were male (55.7%) and white (85.9%) with a median age of 70 years. Most patients had their BCC lesions for 12 months (43.1%) before diagnosis. BCCs were mostly located on the head and neck area (58.1%). In most patients (72.0%), a diagnostic punch biopsy confirmed BCC. Plastic surgeons subsequently excised the BCC lesions in 74.0% of these patients. The most common histological subtype was nodular BCC (74.0%). The National Comprehensive Cancer Network (NCCN) risk of recurrence was approximately evenly distributed between high- (54.1%) and low-risk groups (45.9%). The major high-risk feature was the location (36.6%). Histologically confirmed BCC recurrence occurred in 9 of the 149 patients (3.7%) over three years. Conclusions: BCC represents a high burden of disease in our setting. Compared to existing studies, the BCCs in this study are clinically and histologically similar to international reports.

Clinical and pathological features of acral melanoma in a South African population: A retrospective study.

BACKGROUND: Acral melanoma (AM) is a rare subtype of cutaneous melanoma (CM) that disproportionately affects skin of colour and carries a poorer prognosis than other melanoma subtypes. The poor prognosis is attributed to late diagnosis and subsequent relatively high Breslow thickness, but also to an intrinsic biological aggressiveness. Scientific data on AM from the developing world are limited and a need exists to characterise the disease further in the South African (SA) population. OBJECTIVES: To describe the clinical and pathological features of AM in an SA population. METHODOLOGY: A retrospective chart review characterised the demographics, clinical features and histological data of 66 patients diagnosed with AM between January 2010 and June 2016 at Tygerberg Academic Hospital, Cape Town, SA. RESULTS: Sixty-six patients with AM were identified from 335 patients diagnosed with CM during the set time frame. The mean age (standard deviation (SD)) was 61.5 (12.5) years. Forty-two (63.6%) of the patients were female (male/female ratio 1:1.75). The majority of patients diagnosed with AM were black (48.5%), and the proportion of AM in black patients with CM was 80.0%. Fifty-six AMs (84.8%) were located on the foot and 10 (15.2%) on the hand. The median duration of the lesion before diagnosis was 10 months (range 2 - 84) and the mean (SD) tumour size was 3.8 (2.2) cm at diagnosis. The mean Breslow thickness of all AMs at diagnosis was 5.2 mm (median 4.2  mm, range 0 - 22). Stage of disease was known in 41 patients, 23 (56.1%) of whom had at least stage III disease at diagnosis. Mean Breslow thickness for foot and hand melanomas was 4.9 mm (range 0 - 22) and 6.9 mm (range 0 - 13.3), respectively (p=0.2552). The mean Breslow thickness in the black population was 6.3 mm compared with 4.2 mm and 4.3 mm, respectively, in the white and coloured populations (p=0.178). Patients from outside the Western Cape Province (WC) presented with a mean Breslow thickness of 6.6 mm (range 0 - 14.5) and patients from the WC with a mean Breslow thickness of 4.9 mm (range 0 - 22) (p=0.3602). CONCLUSIONS: AMs accounted for a significant proportion of all CMs diagnosed. Patients presented with an advanced stage of disease at diagnosis, and further studies are needed to further investigate the reasons for delayed diagnosis.

Calcific uraemic arteriolopathy (calciphylaxis) in patients on renal replacement therapy.

BACKGROUND: Calcific uraemic arteriolopathy (calciphylaxis) is an unusual and potentially fatal condition characterised by small-vessel calcification and ischaemic skin necrosis. It mainly affects patients with end-stage renal disease (ESRD) on haemodialysis, but may rarely occur in the absence of ESRD in conditions such as primary hyperparathyroidism, malignancy, alcoholic liver disease and connective tissue disease. METHODS: We reviewed the records of all patients diagnosed with calciphylaxis while on renal replacement therapy at Tygerberg Hospital, Cape Town, South Africa, between 1990 and 2014, to describe its presentation, course and final outcome. RESULTS: Nineteen patients developed calciphylaxis over this period. Their median age was 34 years and 13 (68.4%) were female. Fifteen (78.9%) had received a kidney transplant. All patients had painful skin lesions that rapidly progressed to infarction. Small-vessel calcification was seen on skin biopsy in 13 patients. Twelve patients had hyperparathyroidism. Several of the transplanted patients had been treated for graft rejection in the year preceding the diagnosis. Treatment consisted of good wound care and efforts to normalise serum calcium and phosphate levels. Five patients received an urgent parathyroidectomy. The outcome was fatal in 17 patients, with sepsis being the main cause of death. CONCLUSIONS: In our patients, calciphylaxis carried a worse prognosis than previously reported internationally. It should always be considered in the differential diagnosis of painful skin lesions in the dialysis or transplant patient.

Detection and subtyping of human herpesvirus-8 in renal transplant patients before and after remission of Kaposi's sarcoma.

BACKGROUND: Kaposi's sarcoma (KS) is a complication of renal transplantation. If the human herpesvirus-8 (HHV-8) causes KS, the virus should be present in all KS lesions and be drastically reduced or cleared from involved tissue on remission of the KS. METHODS: Fourteen renal transplant patients with cutaneous KS, including autopsy material from two cases, were investigated for the presence of HHV-8. A second skin biopsy was taken from 11 survivors, after remission of KS, from normal skin in the same anatomical region as the first biopsy. Remission was induced by reduction or cessation of immunosuppression. A peripheral blood sample was collected simultaneously with the repeat biopsy. A nested polymerase chain reaction assay was used to detect HHV-8 DNA in the biopsy tissue and peripheral blood mononuclear cells followed by direct sequencing of polymerase chain reaction product to detect any nucleotide changes. RESULTS: HHV-8 DNA was detected in all the cutaneous KS and all the visceral KS samples, as well as a number of KS-free organs including the thyroid, salivary gland, and myocardium that have not been described before. Mutations in the viral DNA could be demonstrated in all patients. The mutations found were related more to that seen in AIDS-KS cases than that found in African endemic KS cases. HHV-8 sequences could be detected in follow-up frozen skin biopsies of five patients but were negative in the equivalent formalin-fixed specimens. Viral DNA was also detected in 2 of 11 peripheral blood mononuclear cell samples collected at the time of the follow-up skin biopsies. CONCLUSION: Reduction or withdrawal of immunosuppression allows the immune system to recover sufficiently to reduce viral replication with subsequent viral persistence and low grade viral replication that coincides with clinical remission of the KS lesions. This provides further evidence for the important etiological role played by HHV-8 in the pathogenesis of posttransplant KS.

A case of the Neu-Laxova syndrome: prenatal ultrasonographic monitoring in the third trimester and the histopathological findings.

A diagnosis of the Neu-Laxova syndrome was made by ultrasonography in the third trimester of pregnancy. Initial ultrasonographic examination, at approximately 28 wk gestation, showed intrauterine growth retardation (IUGR), hypoechoic skeletal structures, kyphosis, feeble fetal activity, and restricted limb movement. Subsequent sonograms showed microcephaly with a receding forehead and prominent eyes, generalised edema and flexion deformities of limbs. Late third trimester findings included polyhydramnios, swelling and webbing of the knee and elbow joints, and severe edema of the hands and feet, giving the impression of absent digits. The clinical features of this case are consistent with group II of Curry's classification of the Neu-Laxova syndrome [Curry, 1982]. The histopathological findings, a triad of dermatological features, poor cortex formation of the long bones, and central nervous system (CNS) dysgenesis, are discussed. In view of the 25% recurrence rate, at risk pregnancies should be carefully monitored by ultrasonography: at 6-8 wk for accurate dating, at 12-16 weeks for active fetal limb movement, and at 16-24 wk for facial and skeletal anomalies, the detection of IUGR, and polyhydramnios.

Calcific uraemic arteriolopathy (calciphylaxis) in patients on renal replacement therapy

Background. Calcific uraemic arteriolopathy (calciphylaxis) is an unusual and potentially fatal condition characterised by small-vessel calcification and ischaemic skin necrosis. It mainly affects patients with end-stage renal disease (ESRD) on haemodialysis, but may rarely occur in the absence of ESRD in conditions such as primary hyperparathyroidism, malignancy, alcoholic liver disease and connective tissue disease.Methods. We reviewed the records of all patients diagnosed with calciphylaxis while on renal replacement therapy at Tygerberg Hospital, Cape Town, South Africa, between 1990 and 2014, to describe its presentation, course and final outcome.Results. Nineteen patients developed calciphylaxis over this period. Their median age was 34 years and 13 (68.4%) were female. Fifteen (78.9%) had received a kidney transplant. All patients had painful skin lesions that rapidly progressed to infarction. Small-vessel calcification was seen on skin biopsy in 13 patients. Twelve patients had hyperparathyroidism. Several of the transplanted patients had been treated for graft rejection in the year preceding the diagnosis. Treatment consisted of good wound care and efforts to normalise serum calcium and phosphate levels. Five patients received an urgent parathyroidectomy. The outcome was fatal in 17 patients, with sepsis being the main cause of death.Conclusions. In our patients, calciphylaxis carried a worse prognosis than previously reported internationally. It should always be considered in the differential diagnosis of painful skin lesions in the dialysis or transplant patient

Toxic epidermal necrolysis and Stevens-Johnson syndrome in South Africa: a 3-year prospective study.

BACKGROUND: Toxic Epidermal Necrolysis (TEN) and Stevens-Johnson syndrome (SJS) remain feared medication-related reactions. HIV infection and tuberculosis predispose to drug eruptions, yet there is a paucity of data on TEN/SJS in populations with high prevalences of both diseases. AIM: The aim of this prospective observational study was to describe the features and outcomes of patients admitted with TEN/SJS at a large academic hospital in South Africa. We aimed to identify poor prognostic indicators and to validate the use of the TEN-specific severity-of-illness score (SCORTEN) in this population. METHODS: All patients admitted with TEN/SJS over a 3-year period were enrolled. Disease severity was graded according to percentage skin involved and SCORTEN. Co-morbid diagnoses, clinical features, investigations, complications and outcomes were noted. RESULTS: 75 patients (39.9 ± 10.6 years, 16 males, 59 HIV positive) were classified as TEN (n = 42), TEN/SJS overlap (n = 11) and SJS (n = 22). Twenty-four percent died, most from refractory septic shock. Non-survivors had a higher mean SCORTEN on Days 1 and 3 (1.89 vs. 1.04, P = 0.006 and 2.27 vs. 0.90, P < 0.001). A SCORTEN ≥2 on Days 1 and 3 predicted non-survival (OR = 2.94, P = 0.047; OR = 7.45, P < 0.001). Other predictors of non-survival included HIV infection (OR = 6.01, P = 0.058), HIV-tuberculosis co-infection (OR = 8.5, P < 0.001), ≥40% skin involvement (OR = 20.27, P < 0.001), anaemia (OR = 4.68, P = 0.005), hypoalbuminemia (OR = 8.5, P = 0.001) and severe sepsis (OR = 71.09, P < 0.001). CONCLUSION: Most patients with TEN/SJS were HIV positive and female. We validated the use of SCORTEN and identified several prognostic indicators, most significant being HIV-tuberculosis co-infection, ≥40% skin involvement and severe sepsis.

Guideline on the management of psoriasis in South Africa.

UNLABELLED: BACKGROUND; Psoriasis vulgaris is a chronic, relapsing, immune-mediated, potentially devastating disease, influenced by genetic and environmental factors, that can cause substantial morbidity and psychological stress and have a profound negative impact on patient quality of life. OBJECTIVE: These guidelines for the management of psoriasis have been developed in an attempt to improve the outcomes of treatment of this condition in South Africa. Psoriasis has a major impact on the quality of life of sufferers, and it is expected that these guidelines, if implemented, will play a role in achieving improved outcome. SCOPE: These guidelines were developed to address the diagnosis and treatment of psoriasis, of differing degrees of severity and in patients of all ages, by all health care professionals involved with its management. RECOMMENDATIONS: All health care workers involved in the management of psoriasis should take note of these guidelines and try to implement them in clinical practice as far as possible. All treatment methods and procedures not substantiated by evidence from the literature should be discontinued and avoided to decrease the financial burden of psoriasis treatment. VALIDATION: These guidelines were developed through general consensus by a group of 8 South African dermatologists (the 'Working Group') sanctioned by the Dermatological Society of South Africa (DSSA), by adaptation for the South African situation of the current guidelines used in the USA, the UK, Germany, Canada and Finland. Draft documents were made available for comment to the dermatological community as a whole via the official website of the DSSA, and the guidelines were presented and discussed at the annual congress of the DSSA in 2008. All input from these sources, where appropriate, were then incorporated into these guidelines. GUIDELINES SPONSOR: Schering-Plough initiated the project and sponsored the meetings of the working group and all costs generated by these meetings. PLANS FOR GUIDELINE REVISION: The field of biologicals and cytokine modulators is in a rapid phase of development, and revision of the scope and content of these guidelines will be ongoing as longer-term data emerge.

Secondary syphilis. A clinicopathological study.

Syphilis is still a common disease in many countries. The clinical features of secondary syphilis are well documented, and the histopathological features of secondary syphilis have been reviewed in a few studies. The present study documents the histopathology of secondary syphilis based on 68 skin biopsies from 38 patients. Based on the findings of this study, and a review of the literature, diagnostic guidelines are suggested and the differential diagnoses are discussed.

Acute febrile neutrophilic dermatosis. A histopathological study of 37 patients and a review of the literature.

More than 100 cases of acute febrile neutrophilic dermatosis (AFND) have been documented since the original description by Sweet in 1964. Review articles have focused on clinical features. The present study documents the histopathological features of 54 biopsies obtained from 37 patients with early AFND. All patients fulfilled the criteria for the diagnosis of AFND as suggested by Su and Liu. Macular, papulonodular and scaly, annular, or arciform lesions are represented, histopathologically by lymphocytic, predominantly neutrophilic, and mixed infiltrates with a prominent histiocytic component. Characteristic histopathology--i.e., a pale, edematous epidermis, subepidermal edema with extravasated red cells, and a more or less diffuse infiltrate of mature neutrophilis in the upper dermis without vasculitis--is only found during the neutrophilic phase. This is an important consideration when evaluating sections of patients with possible AFND. AFND is a disease that represents a wide spectrum of clinical and histological features. Implications regarding differential diagnoses are discussed.

Blastomycosis in Namibia--report of a case successfully treated with itraconazole.

The clinical, histological, mycological, radiological and scintigraphic features of a 42-year-old Namibian male with blastomycosis are described. This appears to be the first documented incidence of blastomycosis in Namibia. Leucocyte myeloperoxidase deficiency was evident. Treatment with itraconazole led to dramatic resolution of lesions. A reactive xanthogranulomatous response was present in a healed clavicular lesion.

Follicular mucinosis in association with a melanocytic nevus. A report of two cases.

The recognition of follicular mucinosis as a distinct entity is accorded to Pinkus in a 1957 paper under the title Alopecia mucinosa. A primary and a secondary form is recognised. Recently secondary follicular mucinosis was observed in our laboratory in association with an intradermal and a compound melanocytic nevus. To my knowledge this association has not been reported previously.

Widespread superficial thrombophlebitis as a manifestation of secondary syphilis--a new sign. A report of 2 cases.

Two patients with serologically proven secondary syphilis also showed multifocal superficial thrombophlebitis. All manifestations cleared when appropriate antisyphilitic treatment was instituted. Although Treponema pallidum could not be demonstrated in the thrombophlebitic veins, the organism was considered responsible, either directly or indirectly. Multifocal superficial thrombophlebitis should be regarded as a new sign of secondary syphilis.

Digital papular calcific elastosis: a histopathological, histochemical and ultrastructural study of 20 patients.

In 1960, 5 patients were reported with a condition termed "degenerative collagenous plaques of the hands". Ultraviolet light and chronic pressure seem to be the inciting factors. Clinically, it is characterized by keratotic, translucent papules, in linear array, on the radial border of the hands. Histology shows hyperkeratosis and dermal elastosis. The current study documented the histopathological, histochemical and ultrastructural features of 20 patients with this condition and considered the differential diagnoses. The findings were in accordance with those of previous studies, but peculiar, basophilic elastotic masses (BEMs), were a prominent finding. Ultrastructurally, elastic tissue appeared in the form of degenerated non-fragmented and fragmented elastic fibres, degenerated fibres showing foci of increased density, with or without a fibrillar component and as amorphous, structureless material. BEMs arose almost exclusively from degenerated elastic tissue and contained calcium. Disintegrated collagen may be incorporated in the amorphous material and, subsequently, form a minor part of BEMs. Solar elastosis, and its variants, show some similarity to degenerative collagenous plaques of the hands, but lack the constant presence of these calcified angular elastotic masses. BEMs show resemblance to elastic globes, and elastotic bodies found in elastotic nodules of the anthelix and cartilage-hair hypoplasia. In the clinical setting of "degenerative collagenous plaques of the hands", BEMs seem to be unique and due to their extensive presence serve as a non-specific marker for this condition. Digital papular calcific elastosis therefore seems to be more appropriate nomenclature.