Massachusetts General Hospital

Topical treatments for erythromelalgia.

Erythromelalgia is a rare neurovascular disease that causes episodes of pain, redness, and warmth in the extremities, and can be debilitating. Currently, there is no universally effective treatment for erythromelalgia. As the precise etiology of erythromelalgia remains obscure, presently available treatments are aimed at alleviating erythromelalgia's wide-ranging symptoms. In general, topical therapies for erythromelalgia are preferred for their more limited side effects and for those with contraindications to systemic therapies. This review will summarize the current topical therapies available to treat erythromelalgia and discuss emerging therapies based on our growing understanding of erythromelalgia pathophysiology.

Evaluating efficacy of treatments for erythromelalgia in the setting of biopsy proven small fibre reduction.

Cutaneous manifestations of small fibre polyneuropathy.

Because typical and atypical features of small fibre polyneuropathy (SFN) in the skin have not been fully elucidated, the diagnosis is often made by the exclusion of alternative conditions rather than by its identification as a primary syndrome. The objective of this study was to characterize dermatologic manifestations in patients with SFN. Large retrospective series of biopsy-proven SFN cases seen at the Massachusetts General Hospital and Brigham and Women's Hospital (January 2000 to December 2019). The majority of the 301 participants included presented with at least one cutaneous manifestation [292/301 (97%)]. Pain was most common with 254/301 (84.4%) perceiving this as occurring in the skin. It was frequently described as 'burning' [95/254 (37.4%)] and affected distal [174/254 (68.5%)] slightly more than proximal [111/254 (43.7%)] limbs. Numbness [182/301 (60.5%)], edema [61/301 (20.3%)] and skin colour changes [53/301 (17.6%)], which include redness [23/53 (43%)], also had predominant distal distribution. Characteristic loss of distal hair occurred among 17/29 (59%) those reporting hair loss. Other findings with classic limb involvement, Raynaud's phenomenon [33/301 (11%)] and erythromelalgia [26/301 (8.6%)] were seen. Itch [45/301 (15%)], mostly localized [22/45 (49%)] and localized eczematous dermatitis were also found. SFN has a wide range of clinical features in which the skin is affected, with characteristic findings affecting the extremities.

Clinical and pathologic correlation of cutaneous COVID-19 vaccine reactions including V-REPP: A registry-based study.

Cutaneous reactions after COVID-19 vaccination have been commonly reported; however, histopathologic features and clinical correlations have not been well characterized. We evaluated for a history of skin biopsy all reports of reactions associated with COVID-19 vaccination identified in an international registry. When histopathology reports were available, we categorized them by reaction patterns. Of 803 vaccine reactions reported, 58 (7%) cases had biopsy reports available for review. The most common histopathologic reaction pattern was spongiotic dermatitis, which clinically ranged from robust papules with overlying crust, to pityriasis rosea-like eruptions, to pink papules with fine scale. We propose the acronym "V-REPP" (vaccine-related eruption of papules and plaques) for this spectrum. Other clinical patterns included bullous pemphigoid-like (n = 12), dermal hypersensitivity (n = 4), herpes zoster (n = 4), lichen planus-like (n = 4), pernio (n = 3), urticarial (n = 2), neutrophilic dermatosis (n = 2), leukocytoclastic vasculitis (n = 2), morbilliform (n = 2), delayed large local reactions (n = 2), erythromelalgia (n = 1), and other (n = 5). Cases in which histopathology was available represented a minority of registry entries. Analysis of registry data cannot measure incidence. Clinical and histopathologic correlation allowed for categorization of cutaneous reactions to the COVID-19 vaccine. We propose defining a subset of vaccine-related eruption of papules and plaques, as well as 12 other patterns, following COVID-19 vaccination.

Cutaneous reactions reported after Moderna and Pfizer COVID-19 vaccination: A registry-based study of 414 cases.

Cutaneous reactions after messenger RNA (mRNA)-based COVID-19 vaccines have been reported but are not well characterized. To evaluate the morphology and timing of cutaneous reactions after mRNA COVID-19 vaccines. A provider-facing registry-based study collected cases of cutaneous manifestations after COVID-19 vaccination. From December 2020 to February 2021, we recorded 414 cutaneous reactions to mRNA COVID-19 vaccines from Moderna (83%) and Pfizer (17%). Delayed large local reactions were most common, followed by local injection site reactions, urticarial eruptions, and morbilliform eruptions. Forty-three percent of patients with first-dose reactions experienced second-dose recurrence. Additional less common reactions included pernio/chilblains, cosmetic filler reactions, zoster, herpes simplex flares, and pityriasis rosea-like reactions. Registry analysis does not measure incidence. Morphologic misclassification is possible. We report a spectrum of cutaneous reactions after mRNA COVID-19 vaccines. We observed some dermatologic reactions to Moderna and Pfizer vaccines that mimicked SARS-CoV-2 infection itself, such as pernio/chilblains. Most patients with first-dose reactions did not have a second-dose reaction and serious adverse events did not develop in any of the patients in the registry after the first or second dose. Our data support that cutaneous reactions to COVID-19 vaccination are generally minor and self-limited, and should not discourage vaccination.

Acute monophasic erythromelalgia pain in five children diagnosed as small-fiber neuropathy.

The small-fiber polyneuropathies (SFN) are a class of diseases in which the small thin myelinated (Aδ) and/or unmyelinated (C) fibers within peripheral nerves malfunction and can degenerate. SFN usually begins in the farthest, most-vulnerable axons, so distal neuropathic pain and symptoms from microvascular dysregulation are common. It is well known in adults, e.g. from diabetes, human immunodeficiency virus, or neurotoxins, but considered extremely rare in children, linked mostly with pathogenic genetic variants in voltage-gated sodium channels. However, increasing evidence suggests that pediatric SFN is not rare, and that dysimmunity is the most common cause. Because most pediatric neurologists are unfamiliar with SFN, we report the diagnosis and management of 5 Swiss children, aged 6-11y, who presented with severe paroxysmal burning pain in the hands and feet temporarily relieved by cooling-the erythromelalgia presentation. Medical evaluations revealed autoimmune diseases in 3 families and 3/5 had preceding or concomitant infections. The standard diagnostic test (PGP9.5-immunolabeled lower-leg skin biopsy) confirmed SFN diagnoses in 3/4, and autonomic function testing (AFT) was abnormal in 2/3. Blood testing for etiology was unrevealing, including genetic testing in 3. Paracetamol and ibuprofen were ineffective. Two children responded to gabapentin plus mexiletine, one to carbamazepine, two to mexiletine plus immunotherapy (methylprednisolone/IVIg). All recovered within 6 months, remaining well for years. These monophasic tempos and therapeutic responses are most consistent with acute post-infectious immune-mediated causality akin to Guillain-Barré large-fiber polyneuropathy. Skin biopsy and AFT for SFN, neuropathic-pain medications and immunotherapy should be considered for acute sporadic pediatric erythromelalgia.

Evidence of small-fiber polyneuropathy in unexplained, juvenile-onset, widespread pain syndromes.

We tested the hypothesis that acquired small-fiber polyneuropathy (SFPN), previously uncharacterized in children, contributes to unexplained pediatric widespread pain syndromes. Forty-one consecutive patients evaluated for unexplained widespread pain beginning before age 21 had medical records comprehensively analyzed regarding objective diagnostic testing for SFPN (neurodiagnostic skin biopsy, nerve biopsy, and autonomic function testing), plus histories, symptoms, signs, other tests, and treatments. Healthy, demographically matched volunteers provided normal controls for SFPN tests. Age at illness onset averaged 12.3 ± 5.7 years; 73% among this poly-ethnic sample were female (P = .001). Sixty-eight percent were chronically disabled, and 68% had hospitalizations. Objective testing diagnosed definite SFPN in 59%, probable SFPN in 17%, and possible SFPN in 22%. Only 1 of 41 had entirely normal SFPN test results. Ninety-eight percent of patients had other somatic complaints consistent with SFPN dysautonomia (90% cardiovascular, 82% gastrointestinal, and 34% urologic), 83% reported chronic fatigue, and 63% had chronic headache. Neurologic examinations identified reduced sensation in 68% and vasomotor abnormalities in 55%, including 23% with erythromelalgia. Exhaustive investigations for SFPN causality identified only history of autoimmune illnesses in 33% and serologic markers of disordered immunity in 89%. Treatment with corticosteroids and/or intravenous immune globulin objectively and subjectively benefited 80% of patients (12/15). More than half among a large series of patients with childhood-onset, unexplained chronic widespread pain met rigorous, multitest, diagnostic criteria for SFPN, which extends the age range of acquired SFPN into early childhood. Some cases appeared immune-mediated and improved with immunomodulatory therapies.