Review articleParkinson's disease and skin
Introduction
Parkinson's disease (PD) is the most common type of parkinsonism and the second most common progressive neurodegenerative disorder with a 1–2% lifetime risk [1,2]. It is chiefly characterized by motor symptoms (e.g. bradykinesia, tremor, rigidity, and postural instability) and non-motor symptoms (e.g. cognitive decline, depression, anxiety, overactive bladder, constipation, sialorrhea, and skin disorders). Non-motor symptoms may precede the diagnosis of PD, sometimes by several years or decades, and can be associated with substantial morbidity [3].
Skin disorders in PD are of particular interest for several reasons. Melanoma, seborrheic dermatitis (SD), sweating dysfunction, and bullous pemphigoid (BP) are overrepresented in PD [[4], [5], [6]]. Some skin disorders such as SD [7] and sweating dysfunction [8] may in part be due to peripheral autonomic dysfunction and can predate onset of PD motor symptoms. Melanoma [9] and BP [10], which seem to have a more complex relation to PD, often develop years after the diagnosis of PD has been established. As these conditions can have implications on the patient's quality of life and prognosis, a high index of suspicion for PD in certain skin disorders and vice versa is therefore critically important. Skin conditions may also be seen as a consequence of oral, parenteral, and surgical therapies for PD. Such skin manifestations may be directly attributable to certain medications used in the treatment of PD, while in other cases complications related to drug delivery or therapeutic procedures may be the cause (e.g. transdermal patches, subcutaneous injection, percutaneous endoscopic gastrostomy for levodopa/carbidopa intestinal gel, and implantation of hardware in deep brain stimulation [DBS]). α-synuclein (α-syn), which plays a central role in PD pathogenesis [11], has been demonstrated over the past few decades to be present in multiple peripheral tissues, including skin [12,13]. This small protein (140 amino acids), involved in a variety of cellular mechanisms, undergoes misfolding and aggregation in the brain as well as in the skin [14], and may contribute to some non-motor symptoms [15]. In recent years, skin biopsy has emerged as a potential biomarker and promising tool for diagnosis of α-synucleinopathies [16]. Furthermore, as discussed later, skin may even have therapeutic implications as a source of stem cells [17,18].
In this article we aim to provide an updated review of skin disorders associated with PD and skin-related complications of anti-parkinsonian therapy (Table 1, Table 2). We also discuss the role of skin in pathogenic, diagnostic, and therapeutic considerations in PD.
Section snippets
Methods
We conducted a review of English-language publications indexed on PubMed until June 2020 with the following search terms: Parkinson's disease OR parkinsonism AND each of the following search terms (or combinations thereof): skin, diagnosis, biopsy, sensory, autonomic, alpha synuclein, dermatitis, neuropathy, seborrhea, seborrheic dermatitis, sweat, hyperhidrosis, hypohidrosis, pemphigoid, rosacea, melanoma, cancer, nodules, treatment, levodopa, dopamine agonist, ropinirole, rotigotine,
Melanoma
Melanomas are malignant, pigmented tumors that arise from melanocytes typically in the skin (cutaneous melanoma) and occasionally from non-dermal melanocytes (Fig. 1). Their diagnosis can be suspected based upon visual inspection as they are characterized by asymmetry, border irregularity, color variability, large diameter, and evolution over time (the “ABCDE's”). Several types of melanomas are recognized, including those that arise from pre-existing moles (superficial spreading melanoma), de
Levodopa
Carbidopa-levodopa therapy is the first line therapy for motor symptoms related to PD [174]. Use of the medication rarely leads to any skin-related manifestations and is otherwise generally well tolerated. Lower extremity edema has been noted in 1–2% of patients across clinical trials [175]. There are also reports of an allergic reaction to levodopa therapy manifesting as a generalized pruritic maculopapular rash that subsequently resolves with discontinuation of levodopa treatment, however, it
Diagnosis of Parkinson's disease
The neuropathological hallmark of PD consists of marked loss of pigmented dopaminergic neurons in the substantia nigra and abnormal filamentous inclusions of α-syn as the major component of Lewy pathology (LP), including Lewy bodies (neuronal cytoplasmic inclusions) and Lewy neurites (in neuronal processes) [2,237]. However, the diagnosis of PD in life is based on clinical criteria [238,239] with a diagnostic accuracy of about 70–80% compared with the neuropathological gold standard even when
Conclusion
Skin-related manifestations of PD are common and well documented in the literature. However, these disorders are often overlooked or disregarded by practitioners, including neurologists and dermatologists. Conditions such as SD or sweating dysfunction may precede the diagnosis of PD and could serve as potential diagnostic clue in early presentation of the conditions. As with other manifestations of PD, these conditions should not be dismissed as SD and sweating dysfunction may be responsive to
Funding
There is no funding for this review but the authors wish to acknowledge the support of Parkinson's Foundation for their Centers of Excellence.
Ethics approval: N/A
Consent to participate: N/A (patients depicted in Fig. 1, Fig. 2, Fig. 3, Fig. 4, Fig. 5 completed a written consent form prior to photography; however, this is not felt to be needed since the patients cannot be identified based on their pictures).
Consent for publication: N/A.
Availability of data and material: N/A.
Code availability: N/A.
Author contributions
Nicki Niemann, MD: Conceptualized study, drafted the manuscript for intellectual content.
Andrew Billnitzer, MD: Drafted the manuscript for intellectual content.
Joseph Jankovic, MD: Conceptualized study, revised the manuscript for intellectual content.
Declaration of competing interest
Nicki Niemann: None.
Andrew Billnitzer: None.
Joseph Jankovic: Dr. Jankovic has received research and/or training grants from: Adamas Pharmaceuticals, Inc; Allergan, Inc; Biotie Therapies; CHDI Foundation; Civitas/Acorda Therapeutics; Dystonia Coalition; Dystonia Medical Research Foundation; F. Hoffmann-La Roche Ltd; Huntington Study Group; Kyowa Haako Kirin Pharma, Inc; Medtronic Neuromodulation; Merz Pharmaceuticals; Michael J Fox Foundation for Parkinson Research; National Institutes of
Acknowledgements
The images in (Fig. 1, Fig. 2) were kindly provided by Soo Jung Kim, MD, and Jennifer C. Martin, MD, Department of Dermatology, Baylor College of Medicine, Houston, Texas.
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