Brandon W. Muse

Aquagenic pruritus (AP) is a rare itch disorder with limited effective treatments, and emerging clinical observations suggest that oral β-alanine may reduce symptoms. The purpose of this viewpoint is to propose a biologically plausible mechanism through which β-alanine may alleviate primary AP. We reviewed published case reports and patient-reported survey data describing β-alanine use in AP and integrated these clinical observations with experimental data on MAS-related G protein–coupled receptor D (MrgprD)–expressing sensory neurons and their role in mast-cell regulation. Published case reports describe marked improvement in water-induced pruritus following prophylactic oral β-alanine administration, and a recent survey of patients with idiopathic AP reported substantial symptom relief among β-alanine users. Preclinical data indicate that MrgprD-neuronal glutamate release suppresses mast cell hyperresponsiveness, suggesting a potential pathway for the observed antipruritic effect. Additional mechanisms, including β-alanine metabolism to carnosine and its potential mast cell–stabilizing effects, may also contribute. β-alanine may act through modulation of a nonhistaminergic neuroimmune circuit and represents a promising therapeutic candidate for further investigation in AP.

Background and Clinical Significance: Hell’s Itch is a rare, intensely uncomfortable post-sunburn condition with burning pruritus emerging 24–72 h after UV exposure. This condition often goes unrecognized and is frequently misdiagnosed by healthcare providers due to a lack of knowledge and familiarity. Standard antipruritic measures are often ineffective, and patients frequently rely on anecdotal self-management. Case Presentation: Three healthy adult males between 23 and 28 years old experienced multiple episodes of delayed-onset intense pruritus following moderate-to-severe sun exposure. The patients experienced a burning or stinging pain which they described as “fire ants” or “thumbtacks,“ and their symptoms started between 24 and 72 h after sun exposure without any rash or fever symptoms. The patients did not achieve symptom relief from standard treatments which included oral antihistamines and topical lidocaine, NSAIDs, aloe vera, and cold compresses. The patients received β-alanine treatment through pre-workout supplements or pure powder after consulting non-clinical sources. Each patient ingested β-alanine and reported rapid relief (itch 8–10/10 → 1–2/10) lasting 2–3 h. The only adverse effect reported by one patient was mild paresthesia. Conclusions: This case introduces β-alanine as a potential off-label therapy for Hell’s Itch and emphasizes the psychological burden and clinical complexity of the condition. While anecdotal, further study is needed to elucidate the mechanism of action of β-alanine in relieving symptoms of Hell’s Itch, as well as assess safety and efficacy in controlled settings. Increased clinical awareness of Hell’s Itch may reduce patient distress and improve management strategies.

Journal of Medical Internet Research - International Scientific Journal for Medical Research, Information and Communication on the Internet #Preprint #PeerReviewMe: Warning: This is a unreviewed preprint. Readers are warned that the document has not been peer-reviewed by expert/patient reviewers or an academic editor, may contain misleading claims, and is likely to undergo changes before final publication, if accepted, or may have been rejected/withdrawn. Readers with interest and expertise are encouraged to sign up as peer-reviewer, if the paper is within an open peer-review period. Please cite this preprint only for review purposes or for grant applications and CVs (if you are the author). Background: Hell's Itch (HI) is a poorly understood condition triggered by UV exposure, while Aquagenic Pruritus (AP) causes severe itching after water exposure. Both conditions are distinct from other photosensitive disorders due to the lack of skin changes. Objective: To investigate the clinical characteristics of HI and compare them with AP, analyzing similarities and differences in symptom occurrence and severity. Methods: Cross-sectional surveys were conducted within HI and AP communities (N=671 and N=254, respectively) to assess symptom occurrence and severity. Results: Both conditions shared similar pruritus severity. However, pain severity was significantly different, with HI participants reporting more intense pain (92.23%, severity 7.45) compared to AP (39.91%, severity 6.35, P=.0003). Conclusions: The findings suggest potential shared pathogenic mechanisms between HI and AP, emphasizing the need for further research to improve diagnosis and treatment strategies.

BACKGROUND Hell's Itch (HI) is a poorly understood condition triggered by UV exposure, while Aquagenic Pruritus (AP) causes severe itching after water exposure. Both conditions are distinct from other photosensitive disorders due to the lack of skin changes. OBJECTIVE To investigate the clinical characteristics of HI and compare them with AP, analyzing similarities and differences in symptom occurrence and severity. METHODS Cross-sectional surveys were conducted within HI and AP communities (N=671 and N=254, respectively) to assess symptom occurrence and severity. RESULTS Both conditions shared similar pruritus severity. However, pain severity was significantly different, with HI participants reporting more intense pain (92.23%, severity 7.45) compared to AP (39.91%, severity 6.35, P=.0003). CONCLUSIONS The findings suggest potential shared pathogenic mechanisms between HI and AP, emphasizing the need for further research to improve diagnosis and treatment strategies.

Nausea and vomiting during pregnancy (NVP), particularly its severe form, Hyperemesis gravidarum (HG), affects up to 70% of pregnancies and significantly impacts the quality of life for those with the condition as well as generates a great economic burden, with annual costs exceeding $1.7 billion in the United States. Despite the available treatments targeting neurotransmitters like serotonin and dopamine, many patients experience inadequate relief and suffer from severe side effects, including headaches and dizziness. Recent research has underscored the role of GDF15, a protein mainly produced by the placenta and linked to NVP symptoms. This protein, part of the TGF-β superfamily, has been implicated in appetite and weight regulation and is altered in those with HG due to specific genetic mutations. Addressing the challenges of delivering effective treatments, current innovations focus on targeting GDF15 to reduce symptoms while ensuring fetal safety. Promising therapeutic strategies include non-IgG immunotherapies, small peptide and molecule antagonists, and novel administration methods such as transdermal patches. These approaches aim to optimize dosage and reduce adverse effects. The effective development and testing of these treatments necessitate advanced animal models that closely resemble human pregnancy physiology, highlighting the need for further research and funding. This ongoing research holds significant potential to improve the clinical outcomes for HG patients and decrease the economic impact on healthcare systems, urging a dedicated response from the scientific and medical communities to advance these promising treatments.

Journal of Medical Internet Research - International Scientific Journal for Medical Research, Information and Communication on the Internet #Preprint #PeerReviewMe: Warning: This is a unreviewed preprint. Readers are warned that the document has not been peer-reviewed by expert/patient reviewers or an academic editor, may contain misleading claims, and is likely to undergo changes before final publication, if accepted, or may have been rejected/withdrawn. Readers with interest and expertise are encouraged to sign up as peer-reviewer, if the paper is within an open peer-review period. Please cite this preprint only for review purposes or for grant applications and CVs (if you are the author). -

UNSTRUCTURED We present a survey-based exploration of Hell’s Itch, a severe dermatologic reaction often mistaken for sunburn, that reveals distinct symptoms including intense pain, unrelenting itching, paresthesia, and even suicidal ideation, differentiating it from a typical sunburn.