A 32-year-old woman presented with a painless but cosmetically bothersome chronic indolent lesion on her left knee. The lesion arose from a previous wound site that developed about four weeks following a fall 20 years prior in the coral reefs of New Zealand. She was systemically well and had no significant medical or family history. On examination, there was a large (about 9 × 5 cm in size), well defined pink plaque over the left patella with a hyperkeratotic, crusted and verrucous surface (Box 1). Surrounding the wound were areas of post-inflammatory hyperpigmentation. There were no other skin lesions nor associated lymphadenopathy. Initial differential diagnoses included keloid scarring, atypical mycobacterial or deep fungal infection, cutaneous malignancy, and granulomatous disease. A punch biopsy was subsequently performed. Histopathology showed epidermal hyperplasia, dermal inflammation consisting of lymphocytic infiltrates with a focal granulomatous component, and scarring within the deeper dermis (Box 2, A and B). There was no evidence of fungal organisms or acid-fast bacilli on periodic acid-Schiff and Ziehl–Neelsen staining respectively. After a five-week incubation period, tissue culture with Ziehl–Neelsen stain confirmed the presence of M. marinum (Box 3). No treatment was administered pending culture results. * A few neutrophils, eosinophils, and plasma cells are also seen. There is scarring within the deeper dermis (A: haematoxylin and eosin stain, × 200; B: haematoxylin and eosin stain, × 400). The diagnosis of cutaneous M. marinum infection was made after correlating the clinical history, histopathological findings, and culture results. After consultation with an infectious diseases specialist, the patient was commenced on doxycycline, clarithromycin and rifampicin for a minimum of six weeks before being lost to follow-up. Furthermore, she was referred to plastic surgery for consideration of additional surgical resection due to the lesion's extent, but failed to attend her consultation. Mycobacterium marinum is a slow growing, non-tuberculous, acid-fast, non-motile bacillus that thrives in temperate, hot and humid aquatic environments.1 Inoculation can occur through occupational and recreational exposure, typically following a traumatic injury in a contaminated salt- or freshwater environment.2, 3 The association with fish tanks is classical, earning the disease the moniker “fish tank granuloma”.2 In a series of 63 cases from France, 84% were linked to fish tank exposure.3, 4 In Australia, however, exposure to M. marinum is more likely to occur from outdoor activities. The clinical appearance is a solitary, red-to-violaceous papule, nodule or plaque on the extremities.3, 4 The surface may be crusted or verrucous and may progress to ulceration or disseminated infection in severe cases.4 The infection may extend to deeper tissues, causing tenosynovitis, osteomyelitis or septic arthritis.1 Affected individuals may delay seeking treatment for several months, as infection can be indolent and painless.2, 3 Lesions may also heal spontaneously.5 The diagnosis is made by culturing the organism from tissue biopsy. Growth occurs after a median incubation period of 21 days (range, 5–210 days) in Löwenstein–Jensen agar culture at 28–32°C.4 Polymerase chain reaction amplification techniques using Mycobacterium genus-specific primers have emerged as a rapid diagnostic test, enabling identification of M. marinum directly from the tissue sample.1 On microscopy, M. marinum appears as a non-motile pleomorphic rod with branching. It is photochromogenic, with colonies turning yellow to orange on exposure to light.3 Ziehl–Neelsen stain will show acid-fast bacilli, but yield can be difficult as the number of mycobacteria in clinical specimens is low.2, 6 It is important to culture biopsies to allow for differentiation from other non-tuberculous mycobacterial infections (Mycobacterium avium-intracellulare, Mycobacterium abscessus, Mycobacterium fortuitum, Mycobacterium chelonae) which can also present as chronic non-healing wounds.7 There is no standard treatment for M. marinum infection. Rifampicin is the most effective drug reported based on MIC90 (concentration that inhibited growth of 90% of isolates) below 0.5 mg/mL.4 Mild infections limited to the skin and soft tissue have been treated effectively with tetracyclines (minocycline and doxycycline). Clarithromycin has also been used successfully both as monotherapy for superficial lesions and as part of a multidrug regimen for deeper infections.1, 4, 5 Other drugs with reported efficacy include ethambutol, trimethoprim/sulfamethoxazole, imipenem, linezolid, ciprofloxacin and moxifloxacin.5 Amikacin has been reported as an effective addition to a multidrug regimen in refractory cases.4, 5 Input from an infectious diseases specialist should be sought. The number of agents and the duration of therapy are often proportionate to the burden of disease, clinical response and immune status.5 Single drug therapy may be effective for mild superficial disease, with multidrug therapy (with or without surgical debridement) favoured for extensive disease.5 Treatment duration should then be tailored to response, noting that the rate of clinical response is variable; at least four to six weeks of therapy should be administered before inadequate response should be suspected.4, 5 Surgical treatment allows for source control of infection, preservation of limb function and better cosmetic outcomes.5 M. marinum infection is very rare; in a series of 260 aquatic wounds in tropical Australia, there was not a single case of M. marinum identified.8 Although rare, one should consider M. marinum infection in chronic indolent lesions with a history of trauma in an aquatic environment, as in our case. The patient gave written consent for publication. We thank Louis Pool, Dermatopathologist at Sullivan Nicolaides Pathology, for provision of the histopathology images and commentary, and Meryta May, Paediatric Infectious Disease Specialist and Microbiologist at Sullivan Nicolaides Pathology, for provision of the microscopy images and commentary used in this article. Open access publishing facilitated by The University of Queensland, as part of the Wiley – The University of Queensland agreement via the Council of Australian University Librarians. No relevant disclosures. Not commissioned; externally peer reviewed.

The main carcinogen for keratinocyte skin cancers (KCs) such as basal and squamous cell carcinomas is ultraviolet (UV) radiation. There is growing evidence that accumulation of mutations and clonal expansion play a key role in KC development. The relationship between UV exposure, epidermal mutation load, and KCs remains unclear. Here, we examined the mutation load in both murine (n = 23) and human (n = 37) epidermal samples. Epidermal mutations accumulated in a UV dose-dependent manner, and this mutation load correlated with the KC burden. Epidermal ablation (either mechanical or laser induced), followed by spontaneous healing from underlying epithelial adnexae reduced the mutation load markedly in both mouse (n = 8) and human (n = 6) clinical trials. In a model of UV-induced basal cell carcinoma, epidermal ablation reduced incident lesions by >80% (n = 5). Overall, our findings suggest that mutation burden is strongly associated with KC burden and represents a target to prevent subsequent KCs.

Risk prediction tools have been developed for keratinocyte cancers (KCs) to effectively categorize individuals with different levels of skin cancer burden. Few have been clinically validated nor routinely used in clinical settings.

LINKED ARTICLE:Burgin et al. Br J Dermatol 2021; 185:473-4.

Dupilumab is currently the only biologic treatment approved for moderate-to-severe atopic dermatitis. Though limited, available clinical data describing dupilumab use in pregnancy have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Systemic treatment in pregnant women with atopic dermatitis is currently restricted to corticosteroids, cyclosporine A, and azathioprine. Atopic dermatitis often has a deleterious course in pregnancy which can cause substantial distress and significantly impact on global health and quality of life. We report a case of severe atopic dermatitis treated safely with dupilumab during pregnancy with no adverse maternal or fetal outcomes observed. Our case highlights that dupilumab use in pregnancy has its place but should always be preceded by careful assessment of the risks and benefits. Clinicians are encouraged to enroll their patients in relevant pregnancy registry studies to monitor outcomes in women exposed to dupilumab during pregnancy and lactation.

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