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Cancer Diagnosis and Pathology Group, Kolling Institute, Sydney, New South Wales, Australia
Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia
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Cancer Diagnosis and Pathology Group, Kolling Institute, Sydney, New South Wales, Australia
Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia
Department of Diabetes and Endocrinology, Nepean Hospital, Kingswood, New South Wales, Australia
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Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia
NSW Health Pathology, Department of Anatomical Pathology, Royal North Shore Hospital, St Leonards, New South Wales, Australia
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Cancer Diagnosis and Pathology Group, Kolling Institute, Sydney, New South Wales, Australia
Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia
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Summary
Necrobiosis lipoidica (NL) is a rare and chronic disease characterised by yellow-brown, atrophic, telangiectatic plaques usually located on the lower extremities, with pathological features of collagen necrobiosis and dermal inflammation. Most cases are seen in those with diabetes mellitus, particularly type 1 diabetes (T1DM), and many without diabetes have evidence of abnormal glucose tolerance or family history of autoimmune disease. In this study, we describe four patients with NL and T1DM. A common theme is late identification and delay in diagnosis. Hence, we discuss the clinical features, need for clinicopathological correlation, and the management and prognostic implications for this distinctive entity. While most remain relatively asymptomatic, others progress to debilitating disease with pruritus, dysesthesia, and pain. Pain is often intense in the presence of ulcerated plaques, a morbid complication of NL. Diagnosis requires the integration of both clinical and histopathological findings. NL has proven a challenging condition to treat, and despite the numerous therapeutic modalities available, there is no standard of care. Hence, in this study, we provide an overview of current management strategies available for NL.
Learning points
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Necrobiosis lipoidica (NL) is classically seen in patients with type 1 diabetes.
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Koebner phenomenon, defined as the appearance of new skin lesions on previously unaffected skin secondary to trauma, is a well-recognised feature in NL.
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Background skin phototype contributes to variable yellow appearance of lesions in NL.
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Diagnosis of NL requires careful clinicopathological correlation.
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NL is a chronic disease often refractory to treatment leading to significant morbidity for the patient and a management conundrum for the multidisciplinary healthcare team.
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No standard therapeutic regimen has been established for the management of NL.
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University of Melbourne, Parkville, Victoria, Australia
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Summary
Acanthosis nigricans (AN) is a common dermatosis associated with hyperinsulinemia and insulin resistance. However, AN has been rarely reported in patients with insulinoma, a state of persistent hyperinsulinemia. We present a case of metastatic insulinoma, in whom AN manifested after the first cycle of peptide receptor radionuclide therapy (PRRT). A 40-year-old man was diagnosed with metastatic insulinoma after 5 months of symptomatic hypoglycemia. Within 1 month post PRRT, the patient became euglycemic but developed a pigmented, pruritic rash which was confirmed on biopsy as AN. We discuss the rare manifestation of AN in subjects with insulinoma, the role of insulin in the pathogenesis of AN, malignant AN in non-insulin-secreting malignancies and association with other insulin-resistant endocrinopathies such as acromegaly.
Learning points
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Acanthosis nigricans (AN) is a common dermatosis which is typically asymptomatic and associated with the hyperinsulinemic state.
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Malignant AN can rapidly spread, cause pruritus and affect mucosa and the oral cavity.
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AN is extremely rare in patients with insulinoma despite marked hyperinsulinemia.
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Peptide receptor radionuclide therapy might have triggered TGF-α secretion in this subject which led to malignant AN.
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Rapid spread or unusual distribution of pruritic AN warrants further investigation to exclude underlying malignancy.
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School of Medicine and Dentistry, James Cook University, Cairns, Queensland, Australia
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School of Medicine and Dentistry, James Cook University, Cairns, Queensland, Australia
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School of Medicine and Dentistry, James Cook University, Cairns, Queensland, Australia
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Summary
Diabetes mellitus is a well-recognised risk factor for melioidosis, the disease caused by Burkholderia pseudomallei, which is endemic in northern Australia and Southeast Asia. We present the initial diagnostic dilemma of a febrile patient from northern Australia with type 1 diabetes mellitus and negative blood cultures. After a 6-week history of fevers and undifferentiated abdominal pain, MRI of her spine revealed a psoas abscess. She underwent drainage of the abscess which cultured B. pseudomallei. She completed 6 weeks of intravenous (IV) ceftazidime and oral trimethoprim/sulphamethoxazole (TMP/SMX) followed by a 12-week course of oral TMP/SMX. We postulate that the likely route of infection was inoculation via her skin, the integrity of which was compromised from her insulin pump insertion sites and an underlying dermatological condition.
Learning points:
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Diabetes mellitus is the strongest risk factor for developing melioidosis.
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Atypical infections need to be considered in individuals with diabetes mellitus who are febrile, even if blood cultures are negative.
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There is heterogeneity in the clinical presentation of melioidosis due to variable organ involvement.
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Consider melioidosis in febrile patients who have travelled to northern Australia, Asia and other endemic areas.
Concord Clinical School, The University of Sydney, Sydney, New South Wales, 2139, Australia
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Concord Clinical School, The University of Sydney, Sydney, New South Wales, 2139, Australia
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Concord Clinical School, The University of Sydney, Sydney, New South Wales, 2139, Australia
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Summary
X-linked adrenoleukodystrophy (X-ALD) is a rare genetic condition caused by mutations in the ABCD1 gene that result in accumulation of very long chain fatty acids (VLCFAs) in various tissues. This leads to demyelination in the CNS and impaired steroidogenesis in the adrenal cortex and testes. A 57-year-old gentleman was referred for the assessment of bilateral gynaecomastia of 6 months duration. He had skin hyperpigmentation since 4 years of age and spastic paraparesis for the past 15 years. Physical examination findings included generalised hyperpigmentation (including skin, buccal mucosa and palmar creases), blood pressure of 90/60 mmHg, non-tender gynaecomastia and bilateral hypoplastic testes. Lower limb findings were those of a profoundly ataxic gait associated with significant paraparesis and sensory loss. Primary adrenal insufficiency was confirmed and investigations for gynaecomastia revealed normal testosterone with mildly elevated luteinising hormone level and normal prolactin. The combination of primary adrenal insufficiency (likely childhood onset), partial testicular failure (leading to gynaecomastia) and spastic paraparesis suggested X-ALD as a unifying diagnosis. A serum VLCFA panel was consistent with X-ALD. Subsequent genetic testing confirmed the diagnosis. Treatment with replacement doses of corticosteroid resulted in improvement in blood pressure and increased energy levels. We have reported the case of a 57-year-old man with a very late diagnosis of X-ALD manifested by childhood onset of primary adrenal insufficiency followed by paraparesis and primary hypogonadism in adulthood. Thus, X-ALD should be considered as a possibility in a patient with non-autoimmune primary adrenal insufficiency and neurological abnormalities.
Learning points
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Adult patients with X-ALD may be misdiagnosed as having multiple sclerosis or idiopathic spastic paraparesis for many years before the correct diagnosis is identified.
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Screening for X-ALD with a VLCFA panel should be strongly considered in male children with primary adrenal insufficiency and in male adults presenting with non-autoimmune primary adrenal insufficiency.
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Confirmation of a genetic diagnosis of X-ALD can be very useful for a patient's family as genetic testing enables detection of pre-symptomatic female heterozygotes who can then be offered pre-natal testing to avoid transmission of the disease to male offsprings.
