Arsenic toxicity is a global health problem affecting many millions of people. Contamination is caused by arsenic from natural geological sources leaching into aquifers, contaminating drinking water and may also occur from mining and other industrial processes. Arsenic is present as a contaminant in many traditional remedies. Arsenic trioxide is now used to treat acute promyelocytic leukaemia. Absorption occurs predominantly from ingestion from the small intestine, though minimal absorption occurs from skin contact and inhalation. Arsenic exerts its toxicity by inactivating up to 200 enzymes, especially those involved in cellular energy pathways and DNA synthesis and repair. Acute arsenic poisoning is associated initially with nausea, vomiting, abdominal pain, and severe diarrhoea. Encephalopathy and peripheral neuropathy are reported. Chronic arsenic toxicity results in multisystem disease. Arsenic is a well documented human carcinogen affecting numerous organs. There are no evidence based treatment regimens to treat chronic arsenic poisoning but antioxidants have been advocated, though benefit is not proven. The focus of management is to reduce arsenic ingestion from drinking water and there is increasing emphasis on using alternative supplies of water.

https://pmj.bmj.com/content/postgradmedj/79/933/391.full.pdf

Acute and chronic arsenic toxicity

No controlled trials of therapy for invasive aspergillosis have been done. This review appraises 2,121 cases reported in 497 articles in the literature and analyzes 440 courses of treatment of infection at various body sites in 379 patients. The exclusion of early failures of therapy skews the results toward a favorable outcome. The rate of response to amphotericin B is 55%. Mortality from pulmonary aspergillosis in bone marrow transplant recipients exceeds 94% regardless of therapy, as does that from cerebral aspergillosis in all hosts. Amphotericin B (1 mg/[kg.d]) with flucytosine lowers mortality in neutropenic patients with pulmonary aspergillosis who did not receive a bone marrow transplant; relapse is common. Surgical debridement of aspergillus maxillary sinusitis is usually curative in nonimmunocompromised patients, whereas it increases mortality among neutropenic patients. Valve replacement is essential for aspergillus endocarditis. Both vitrectomy and intravitreal amphotericin B treatment are essential for aspergillus endophthalmitis. Flucytosine is somewhat useful clinically. Itraconazole shows efficacy in the treatment of pulmonary, skeletal, and pericardial aspergillosis. Although liposomal amphotericin B is less toxic than standard preparations of the drug, relevant data are limited. The proposed potentiation of amphotericin B by rifampin is unsupported by clinical data. Despite "conventional" therapy, mortality from invasive aspergillosis remains high; new approaches must be investigated.

https://www.jstor.org/stable/pdfplus/4455714.pdf

Antifungal and Surgical Treatment of Invasive Aspergillosis: Review of 2,121 Published Cases

The striking impression obtained from reviewing the cancer literature is how difficult it is to analyze the data for answers to many important biologic, behavioral, prognostic, and therapeutic questions about squamous cell carcinoma of the skin. This article addresses current concepts, controversies, and management of cutaneous squamous cell carcinoma (excluding the lip and oral mucosa).

Squamous cell carcinoma of the skin (excluding lip and oral mucosa).

Invasive aspergillosis is rare in immunocompetent people but contributes to significant morbidity and mortality in immunosuppressed patients. The majority (approximately 80%) of invasive Aspergillus infections is caused by Aspergillus fumigatus. The second most frequent (approximately 15-20%) pathogenic species is Aspergillus flavus and to a lesser extent, Aspergillus niger and Aspergillus terreus. Aspergillus flavus has emerged as a predominant pathogen in patients with fungal sinusitis and fungal keratitis in several institutions worldwide. To date, there has not been any publication exclusively reviewing the topic of A. flavus in the literature. This article reviews the microbiology, toxigenicity and epidemiology of A. flavus as well as describes the clinical characteristics, diagnosis and management of infections caused by this organism.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1439-0507.2008.01642.x

Aspergillus flavus: an emerging non-fumigatus Aspergillus species of significance.

Aspergillus spp. produce a wide range of invasive and sapropytic syndromes which may involve any tissue. Within a given tissue or organ the pathology and pathogenesis varies enormously, ranging from angioinvasive disease to noninvasive saprophytic disease. The individual invasive and saprophytic syndromes in which a causative role can be attributed to Aspergillus spp. are detailed specifically with reference to the underlying pathology and pathogenesis, the clinical setting and features, and the manner in which a diagnosis can be established.

The invasive and saprophytic syndromes due to Aspergillus spp

A 6-year-old boy with acute monocytic leukemia and therapy-induced leukopenia developed multiple necrotizing skin lesions where an intravenous administration unit had been secured to his arm and hand. Biopsy and cultures demonstrated Aspergillus flavus as the etiologic agent without evidence of systemic dissemination. Resolution of the infection occurred following systemic amphotericin B therapy and a granulocyte transfusion.

https://www.jaad.org/article/S0190-9622(80)80334-3/pdf

Primary cutaneous aspergillosis.

• A nasopharyngeal carcinoma occurred in a 41-year-old white woman who had received Fowler's solution (potassium arsenite) almost yearly for more than 20 years for the treatment of psoriasis. Palmar and plantar keratoses were present. Because of the rarity of this malignant neoplasm in white people, a relationship with arsenic ingestion is suggested. ( Arch Dermatol 114:602-603, 1978)

Stephen D. Prystowsky

Papers

Primary cutaneous aspergillosis.

Nasopharyngeal Carcinoma Associated With Long-Term Arsenic Ingestion