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Palmoplantar pustulosis (PPP) is an inflammatory skin condition characterized by eruptions of sterile pustules on the palms and/or soles. These eruptions cause significant discomfort and have a major impact on a patient’s quality of life. The exact cause of PPP remains unknown; several theories have been hypothesized. These theories include genetic factors, including mutations in IL36RN, associations with autoimmune/autoinflammatory disorders and drug-induced aetiologies. Tumour necrosis factor (TNF)-α inhibitors are widely used in the treatment of autoimmune conditions such as psoriasis, psoriatic arthritis, rheumatoid arthritis and inflammatory bowel disease. An unusual side-effect of these treatments is their ability to induce paradoxical reactions. It is reported in the literature that this can occur in 2–5% of patients receiving TNF-α inhibition. We report a case of anti-TNF-α-induced paradoxical PPP in a 52-year-old woman with rheumatoid arthritis (RA). Three months after commencing adalimumab for her RA, the patient developed painful sterile pustules on her palms and soles. She was a smoker with no previous history of psoriasis. Her adalimumab treatment was discontinued, and her hands and feet were treated with clobetasol propionate. Despite 3 months of topical treatment and discontinuation of adalimumab, her PPP deteriorated. Interleukin (IL)-17 or IL-23 inhibition was considered but is not indicated for the treatment of RA. To gain control of both her RA and PPP, she was started on tofacitinib 5 mg twice daily, a partial and reversible JAK1 and JAK3 inhibitor. Within 4 days, the pustulosis on her hands and feet improved, and within 3 months, she had total disease clearance with a complete response. Her Dermatology Life Quality Index improved from 23/30 to 0/30. The patient developed a dental abscess on treatment. During this infection, her tofacitinib was withheld for 2 weeks and was treated with metronidazole. During this period, she had an acute flare of her PPP, which quickly resolved once recommencing tofacitinib. In a recent systematic review, a total of 155 patients with biologic-associated paradoxical PPP were identified, with the most common cause being TNF-α inhibition, with female sex, smoking and concomitant autoimmune disorders being major risk factors. To date, only five case reports have described the successful treatment of PPP with tofacitinib. We found that tofacitinib is an effective and rapid treatment for paradoxical PPP.

Ipilimumab, an anti-CTLA-4 monoclonal antibody, is used in the treatment of metastatic melanoma. As with other immune checkpoint inhibitors, it can cause a spectrum of immune-related adverse events (irAEs), including a cutaneous pathology, in 25% of patients. To date, there have been five case reports of Sweet syndrome solely due to ipilimumab therapy. We present a suspected further case in a patient with metastatic melanoma of unknown primary origin, who concurrently developed vitiligo. A 65-year-old man presented to the dermatology department with a 2-week history of a mildly tender, erythematous papulonodular rash localized to the right forearm. He had also developed extensive vitiligo on all limbs over a similar period of time. Histology from a skin punch biopsy demonstrated a predominantly neutrophilic dermal inflammatory infiltrate without features of vasculitis, confirming Sweet syndrome. There were no recent medication changes or disease recurrence on repeat imaging. Nine months prior, the patient had been diagnosed with cerebral and pulmonary metastatic melanoma of unknown primary origin (BRAF V600 mutation positive). He underwent an evacuation of a left temporal cortical mass and subsequent stereotactic radiosurgery. The oncology team then commenced ipilimumab (3 mg kg–1) and nivolumab (1 mg kg–1) every 21 days. Four cycles were completed until discontinuation after 3 months due to multiple severe irAEs, namely, panhypopituitarism and liver toxicity. He was commenced on 80 mg (1 mg kg–1) oral prednisolone, which was slowly reduced over subsequent months and completed a few weeks prior to the development of Sweet syndrome and vitiligo. We prescribed topical clobetasol propionate 0.05% once daily, with resolution of Sweet syndrome after 2 months. The oncology team elected to withhold further immunotherapy due to the multiple irAEs, instead monitoring for melanoma recurrence by serial radiological imaging. The five previously documented cases of ipilimumab-associated Sweet syndrome report an average time to clinical presentation of 8.9 weeks. Our case differs as the patient developed Sweet syndrome 5 months after the discontinuation of immunotherapy. However, the development of any cutaneous adverse effect may have been masked by high-dose steroids for the other systemic irAEs soon after the fourth cycle of treatment. Despite a lack of temporality between immunotherapy and Sweet syndrome in our case, the addition of vitiligo at the same presentation suggests an irAE. This case highlights the importance of monitoring patients on immunotherapy for dermatological side-effects and working closely with oncology colleagues to manage these complex cases.

Hereditary haemochromatosis (HH) is an autosomal recessive disease resulting in excessive levels of iron. In a recent study, in a US population of 448 patients diagnosed with HH, a positive association between HH and nonmelanoma skin cancers (NMSCs) was observed (Pan CX, Yang K, Lau CB et al. Non-melanoma skin cancer in patients with hereditary hemochromatosis: a case–control study. J Am Acad Dermatol 2023; 88:692–4). The authors also reported that, among those who required more frequent venesection, the risk of basal cell carcinoma (BCC) was particularly elevated. In terms of the possible pathomechanism, the authors noted that oxidative stress represents a key component in the pathogenesis of both HH and BCC. Ireland has the highest prevalence of HH in the world, with research suggesting approximately 1 in 83 people is predisposed. For this reason, a study was undertaken to determine if a similar association could be observed in an Irish population. A single-centre retrospective cross-sectional analysis was undertaken on a database of patients with haemochromatosis attending the venesection department of a tertiary referral centre over 25 years (1997–2022). All histologically diagnosed NMSCs within this patient group were then recorded. Ethical approval was granted by the local hospital ethics committee. There were a total 1480 patients in the database, 65% Male (n = 956). Five were excluded due to insufficient data. Thus, 1475 patients were analysed, 64% male (n = 949). The mean current age was 60 years (range: 19–100). Only 52/1475 patients (3.5%) had a histologically diagnosed NMSC, 52% male (n = 27). HH genetic mutation: C282Y homozygous (n = 29); H63D homozygous (n = 5); C282Y/H63D compound heterozygous (n = 11); and data not recorded (n = 7). Mean ferritin at HH diagnosis 575 (range: 0–8413). Forty-three patients were diagnosed with a BCC, 58% male (n = 25), with a total of 94 BCCs. Mean age was 67 years at first NMSC diagnosis. Histological classification: nodular (n = 48); superficial (n = 19); unclassified (n = 18); infiltrative (n = 5); micronodular (n = 3); and basosquamous (n = 1). Eleven patients were diagnosed with a squamous cell carcinoma (SCC), with a total of 21 SCCs. This study had limitations. It was a single-centre, retrospective study analysing only histologically confirmed NMSCs. It is acknowledged that a small proportion of NMSCs may be diagnosed clinically, specifically superficial BCCs without histological confirmation. Only records with histology available in our institution were recorded, and it is possible that NMSCs were excised in other institutions, potentially leading to an under-representation of NMSC incidence. The proportion of patients diagnosed with NMSCs in this cohort was relatively low, in contrast to the findings reported by Pan et al. This study indicates that HH is unlikely to represent an independent risk factor.

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