Bridges, Alina G.

Background: Severe pretibial myxedema (PTM) can be difficult to manage, highlighting the need to investigate newer therapies. Rituximab (RTX) and intravenous immunoglobulin (IVIg) have been tried in Graves' orbitopathy. Since PTM and orbitopathy share a similar underlying pathophysiology, this study aimed to explore these therapies for progressive PTM. Methods: The electronic database was screened for PTM patients evaluated at the Mayo Clinic, Rochester, from 2002 to 2016, and three patients who received IVIg and five who received RTX are reported. PTM pattern was classified as non-pitting edema, plaque and induration, nodular/nummular, and elephantiasis. PTM was confirmed by biopsy in six patients. Results: The patients' median age was 53.8 years, 75% were female, and all but one patient were either active or former smokers. All patients were euthyroid and had progressed despite various therapies prior to starting these agents. Six patients had a plaque and induration pattern, and two had a nodular pattern with elephantiasis. After therapy, six (75%) patients had PTM stability or improvement both subjectively and objectively (80% with RTX and 66% with IVIg). The three patients (one in the IVIg group and two in the RTX group) who had subjective improvement had a plaque pattern. One patient with elephantiasis had a transient response to IVIg and another had stability after RTX. Thyrotropin receptor antibody values and orbitopathy also improved in patients who demonstrated PTM improvement. No serious adverse events were reported, but one patient each had transient hypertension and injection-site thrombophlebitis after IVIg. Conclusions: Immunomodulation therapy was followed by PTM improvement or stability in most patients, with a slightly better response after RTX compared to IVIg. A validated response assessment instrument and larger series of patients are required to determine if the underlying disease process could be curtailed with these agents.

AbstractBackgroundThe occurrence of chemotherapy‐related adverse cutaneous reactions in the setting of capillary leak syndrome (CLS) is quite rare. Our objective was to identify the type of skin reactions associated with CLS.MethodsLeukemia or hematopoietic stem cell transplant patients between January 2010 and December 2017 were identified, and medical records were reviewed for a dermatology consultation occurring concomitantly with CLS.ResultsFive patients were identified, two with a diagnosis of toxic erythema of chemotherapy (TEC) and three others with a skin diagnosis of toxic epidermal necrolysis (TEN). Pathology of all patients was available for clinical‐pathologic confirmation.ConclusionsAlthough TEC is generally self‐limited, both TEC and TEN can present with severe adverse skin manifestations during CLS secondary to toxicity from chemotherapy.

AbstractBlue nevi are common skin neoplasms that typically present as asymptomatic solitary papules, although they may rarely occur in an agminated configuration. We describe a case of agminated blue nevus in a segmental facial distribution associated with soft tissue hypertrophy and hypertrichosis in a 16‐year‐old boy and present a review of the literature. Although they are generally considered to be benign, concurrent soft tissue changes occurring within an agminated blue nevus should be investigated thoroughly to exclude alternate diagnoses.

AbstractBackgroundAcute generalized exanthematous pustulosis (AGEP) is a rare skin condition typically caused by medications. The objective of this study was to examine the clinical features, causes, and outcomes of AGEP at a sole tertiary care center.MethodsA retrospective review of patients with AGEP (European Study of Severe Cutaneous Adverse Reactions score of ≥ 5) seen at Mayo Clinic (Rochester, MN, USA) between January 1, 1996, and December 31, 2013, was conducted.ResultsOf 28 patients (mean age at onset: 56 years), 17 (61%) were women. The development of AGEP was attributed to medications in 25 patients (89%), with clindamycin the most common culprit (six patients). Three patients (11%) had mucous membrane involvement, and 21 (75%) showed systemic involvement. Ten patients (36%) received systemic corticosteroids for treatment of AGEP. Skin findings resolved within 15 days in 26 patients (93%) (mean time to resolution: 7.6 days). In three patients (11%), generalized skin eruptions or dermatitis developed weeks to months after the resolution of AGEP. Twenty‐four patients (86%) had a personal history of drug reactions before the development of AGEP.ConclusionsA previous history of drug reactions and clindamycin causation were more common in the present cohort than in prior reports. A small subset of patients experienced new‐onset non‐AGEP skin eruptions within a few months of the resolution of AGEP.

Background Noonan syndrome with multiple lentigines (NSML), formerly known as LEOPARD syndrome, is an autosomal-dominant disorder characterised by lentigines, EKG abnormalities, ocular hypertelorism, pulmonic stenosis, abnormal genitalia, growth retardation and deafness. There is significant clinical overlap between NSML and other disorders that result from dysregulated rat sarcoma/mitogen-activated protein kinase pathway (RASopathies). Except for neurofibromatosis type 1, other RASopathies are not known to be typically associated with neurogenic tumours. Methods and results We evaluated patients from three families with pigmentary skin lesions, progressive neuropathy, enlarged nerves, massive burden of paraspinal tumours (neurofibroma was confirmed in one patient) and a clinical diagnosis of NSML. All patients had a mutation in the protein tyrosine phosphatase catalytic domain of the PTPN11 gene; two unrelated patients had the p.Thr468Met mutation, while the family consisting of two affected individuals harboured the p.Thr279Cys mutation. Molecular analysis performed on hypertrophic nerve tissue did not disclose a second somatic hit in NF1, PTPN11, NF2 or SMARCB1 genes. Conclusions Neurogenic tumours and hypertrophic neuropathy are unusual complications of NSML and may be an under-recognised manifestation that would warrant surveillance. Our observation may also have implications for other disorders caused by RAS-pathway dysregulation.