CLINICAL REVIEWS

Approach to diagnosis, evaluation, and

treatment of generalized and nonlocal
dysesthesia: A review
Angelina Labib, BS, Olivia Burke, BS, Anna Nichols, MD, PhD, and Andrea D. Maderal, MD

Dysesthesia is an abnormal sensation in the skin that occurs in the absence of any extraordinary stimulus or
other primary cutaneous disorders, excluding any delusions or tactile hallucinations. Clinicians have
characterized dysesthesias to include sensations such as burning, tingling, pruritus, allodynia,
hyperesthesia, or anesthesia. The etiology and pathogenesis of various generalized dysesthesias is largely
unknown, though many dysesthesias have been associated with systemic pathologies including
malignancy, infection, autoimmune disorders, and neuropathies. Dermatologists are often the first-line
clinicians for patients presenting with such cutaneous findings, thus it is crucial for these physicians to be
able to methodically work-up generalized dysesthesias to build a working differential diagnosis, follow up
with key labs and/or imaging, and offer patients evidence-based treatment to relieve their symptoms. This
broad literature review is an attempt to centralize key studies, cases, and series to help guide dermatologists
in their assessment and evaluation of complaints of abnormal cutaneous sensations. ( J Am Acad Dermatol
2023;89:1192-200.)

Key words: CNS neuropathy; generalized dysesthesia; peripheral neuropathy; small nerve fiber
neuropathy.

INTRODUCTION approximately 16% to 25%.2,3 There are numerous

Dysesthesia is a general term that is used to
describe sensations in the skin that are considered
abnormal. Abnormal findings include many different
qualities of sensation that a patient may experience.1
The one shared feature of all dysesthesias is that
although patients experience dermatological
complaints, it is in the absence of primary cutaneous
findings, suggesting an internalized process that
manifests as a skin symptom.1 Dermatologists are
often the first providers in the line of care for
patients; however, the broad differential diagnoses,
lack of knowledge surrounding the pathogenesis,
and scarce treatment guidelines present a clinical
conundrum for both the physician and patient.
There are many different disease processes that
present with generalized dysesthesia, but the main
etiologies can be divided into central, peripheral, or
psychogenic. One study reports that 5% to 11% of
spinal cord injuries result in dysesthesia while
another study found that in sensory strokes, it is
other central nervous system (CNS) related
pathologies that cause dysesthesia.4 Additionally,
dysesthesia is commonly seen in peripheral
neuropathy, which has a prevalence of
approximately 1% to 7%.5,6 One study found that in
patients experiencing dysesthesia of the extremities,
90% demonstrated some degree of peripheral
neuropathy.7 Finally, there are several reports of
dysesthesia of psychogenic etiology8,9; while these
cases are important to consider, history of
psychiatric disorders, negative workups, and the
‘‘diagnosis-of-exclusion’’ model of identification
facilitates clinicians in their diagnosis and
management. Although localized, dysesthesia can
also be associated with neurocutaneous conditions.1
The underlying mechanism of dysesthesia is
largely unknown. The predominant hypothesis of
the pathogenesis of dysesthesia is neurologic
dysfunction.1,10 Ectopic sensory phenomena may
be initiated by spontaneous nerve impulses due to

From the .From the Dr Phillip Frost Department of Dermatology
and Cutaneous Surgery, University of Miami Miller School of
Medicine, Miami, Florida.
Funding sources: None.
IRB approval status: Not applicable.
Patient consent: Not applicable.
Accepted for publication June 27, 2023.
Correspondence to: Andrea D. Maderal, MD, Dr Phillip Frost
Department of Dermatology, University of Miami Hospital
1600 NW 10th Ave RMSB Building 2023A, Miami, FL 33136.
E-mail: AMaderal@med.miami.edu.
Published online July 28, 2023.
0190-9622/$36.00
Ó 2023 by the American Academy of Dermatology, Inc.
https://doi.org/10.1016/j.jaad.2023.06.063

1192
J AM ACAD DERMATOL Labib et al 1193
VOLUME 89, NUMBER 6

inappropriate membrane excitability occurring as a DIFFERENTIAL DIAGNOSES

result of axonal injury in sensory nerves.11 Some Dysesthesia associated with the CNS
studies suggest that ion channels may be CNS-related pathologies that can cause generalized
implicated,11,12 as changes in sodium and potassium dysesthesia can be summarized into vascular,
movement along axons result in paresthesia.13,14 structural, autoimmune, infectious, or inflammatory
One study reports that in chronic axonal damage, etiologies. Stroke and central poststroke syndrome
heterogenous sodium channels may be developing can result in the manifestation of dysesthesia.51,52
along the same nerve and Specifically, infarcts or hem-
activating one another, orrhage that affect sensory
impacting membrane excit- CAPSULE SUMMARY processing regions of the
ability.11 Additionally, tran- brain, including the thalamus
sient receptor potential d
Generalized and nonlocalized and pons, can result in acute
ankyrin 1 has been identified dysesthesia can be delineated into or sub-acute, asymmetric dys-
as a potential molecular central or peripheral etiologies. esthesia occurring during or
component in the mecha- d
Presentation of dysesthesia as well as following the incident.18-21,53
nism of dysesthesia additional findings can help clinicians Impingement of sensory
following decreased periph- deduce the underlying etiology. We pathways in the brain or spi-
eral blood flow.15 provide a robust evaluation with special nal cord can manifest as pro-
Nerve damage and ion considerations to determine the cause of gressive dysesthesia that is at
channel dysfunction may generalized dysesthesia and guide first more localized prior to
also be a result of small fiber management. expanding.34,54,55 Additional
neuropathy, which is a type symptoms include spinal
of pathology that primarily pain and autonomic dysfunc-
affects the myelinated A-delta nerve fibers and un- tion.35,36 Malignancies, radiculopathy, and myelop-
myelinated C-nerve fibers.16 Although the pathogen- athy are few examples.28 Injury to the spinal cord can
esis of small fiber neuropathy is not fully understood, also cause dysesthesia that typically presents at the
it is thought that ischemia, inflammatory cytokines level or below the site of impact.24
(ie, tumor necrosis factor alpha), and oxidative stress Autoimmune conditions, such as multiple
play a role.16 sclerosis (MS), also present with dysesthesia. MS
presents with paroxysmal symptoms anywhere from
1.6% to 17% of the time, including dysesthesia and
CLINICAL FEATURES Lhermitte’s sign.4 While they can occur at any time
Dysesthesia can have variable presentation, and throughout the course of the disease, they may
includes sensations of burning, tingling, stinging, notably signify MS relapse and are the first symptom
tickling, crawling, anesthesia, hypoesthesia, and of MS onset in 24% of cases.4
1 Encephalitis, which is brain tissue inflammation
varying types of pain. Because generalized
dysesthesia is a vague symptom descriptor occurring due to infection or autoimmune processes, is another
from numerous etiologies, it is useful to also identify CNS related pathology that can cause dysesthesia.56-60
additional clinical features occurring in both central Dysesthesia typically presents with the onset of
and peripheral pathologies. encephalitis, although there are cases of later occur-
In CNS pathologies, these features include rence, and is rapidly progressive.33,56,57,59,61
headache, spinal pain, motor weakness, and focal Pathogens that commonly cause infectious encepha-
neurologic deficits. Common additional features of litis are herpes simplex virus, varicella zoster virus,
peripheral neuropathies include a ‘‘stocking enteroviruses, listeria monocytogenes, mycobacte-
and glove’’ pattern, motor dysfunction, and rium tuberculosis, and in certain regions, tick-borne
autonomic dysfunction. A ‘‘stocking and glove’’ encephalitis.62 Typically, infectious encephalitis will
pattern, otherwise known as a length-dependent present with signs of systemic infection such as fever,
presentation, indicates that the dysesthesia occurs first headache, seizures, and altered sense of conscious-
in distal nerves of the hands and feet. This contrasts ness.32 Autoimmune encephalitis is more likely to
with a length-independent distribution of dysesthesia, sub-acutely present with several neurologic and
which is irrespective of proximal or distal nerves. psychiatric signs, such as muscle weakness and
Certain conditions with generalized dysesthesia personality changes.33 In addition to encephalitis,
have specific manifestations, which are outlined in myelitis has also been associated with band-like
Table I.2,4,17-50 dysesthesia.63
1194 Labib et al
Abbreviations used:
CNS: central nervous system
MS: multiple sclerosis
PNS: peripheral nervous system
Another inflammatory etiology causing
dysesthesia is CNS vasculitis, which can be from
systemic (ie, granulomatosis with polyangiitis),
infectious (ie, neurosyphilis, human immunodefi-
ciency virus [HIV]), and autoimmune (ie, sarcoidosis,
systemic lupus erythematous) causes.64 There are
innumerable presentations due to the highly variable
nature of the condition; however, additional identi-
fier symptoms are seizures, focal neurologic deficits,
and a relapsing-remitting disease course.65
Moreover, one nutritional deficiency affecting the
CNS is cobalamin, which results in subacute
combined degeneration, including symmetrical
dysesthesia with proprioception dysfunction and
paraparesis.66
Dysesthesia associated with the peripheral
nervous system (PNS)
Peripheral neuropathy, a cause of dysesthesia
originating from the peripheral nervous system
(PNS), can occur in numerous processes. Although
not traditionally generalized, peripheral neuropathy
is not localized. Radiculopathy or degenerative
changes in the spine affecting the cervical, thoracic,
or lumbar nerve roots present with dysesthesia in
dermatomal patterns that concurrently present with
pain and weakness in analogous myotomes.30
Hereditary Sensory and Autonomic Neuropathies
affect younger individuals, with dysesthesia mostly
occurring in the limbs alongside injuries due to
sensory loss.40,41 Additionally, there is a small sub-
sect of individuals with sensory-predominant forms
of Charcot-Marie-Tooth Disease.67
Diabetic peripheral neuropathy is the most
common among metabolic causes.68 Peripheral
neuropathy in diabetics, occurring in older patient
populations, is symmetric, progressive, and has a
burning quality.42 Prediabetic patients and metabolic
syndrome patients also have peripheral neuropathy
with similar clinical findings.69
There are many infectious etiologies that cause
peripheral neuropathy and nonlocalized
dysesthesia. Viral infection is the most common
infectious origin, including HIV, viral hepatitides,
herpes viruses (ie, cytomegalovirus),70 and
coronavirus71,72; dysesthesia in these conditions
is mostly length-dependent, symmetric, and progres-
sive. Bacterial pathogens, such as Borrelia
J AM ACAD DERMATOL
DECEMBER 2023
burgdorferi and Mycobacterium leprae, have also
been identified as infectious causes of peripheral
neuropathy.73-76
GuillaineBarr
e Syndrome is typically a
postinfectious inflammatory process that causes
peripheral neuropathy that is commonly acute,
ascending, symmetrical motor weakness.77 Although
mostly motor, it has been reported that the earliest
signs of GuillaineBarr
e syndrome are sensory abnor-
malities,77 and there are rare subtypes where sensory
axonal neuropathy is more prominent.46 Other sys-
temic inflammatory and infiltrative processes demon-
strating length-dependent small fiber neuropathy are
sarcoidosis and primary amyloidosis.78,79 Vasculitis is
described as an acute, rapidly progressive inflamma-
tory process with multifocal, asymmetric dysesthe-
sia.80 Dysproteinemias, particularly immunoglobulin
M plasma cell disorders, have a high incidence of
sensory peripheral neuropathy that is chronic, distal,
and symmetric.81
Additionally, there are autoimmune conditions
that have been known to cause peripheral
neuropathy. Sjogren’s syndrome is one notable
cause, displaying dysesthesia that is painful.82,83
Hypothyroidism is another autoimmune condition
that can cause peripheral neuropathy; however, as it
is a rare etiology, there is little known regarding its
presentation.84,85
Drug-induced peripheral neuropathy and chronic
alcohol consumption-related peripheral neuropathy
are toxin-mediated processes where generalized
dysesthesia can be a typical symptom. The most
common drugs that have been associated with
peripheral neuropathy are chemotherapies,
cardiovascular agents, antibiotics, and antiretro-
virals. Affected individuals can experience sensory
phenomena anywhere from weeks to months after
drug initiation.49 Peripheral neuropathy in chronic
alcohol users is very common, with mild forms
occurring approximately in 1 to 5 years and severe
forms following more than 10 years of alcohol
abuse.48 Nutritional deficiencies, namely B vitamins
and copper, have been associated with sensory
neuropathy that is chronic, slowly progressive, and
length-dependent.86,87 We have also encountered
cases of generalized dysesthesia occurring after
inflammatory conditions of the skin such as postviral
exanthem or Drug Rash with Eosinophilia and
Systemic Symptoms (DRESS), though these entities
are not reported in the literature.
Although there are numerous underlying causes
of peripheral neuropathies that can ultimately lead to
sensory phenomena, there is a large proportion of
peripheral neuropathies where no etiology is
identified.88 Up to 40% of patients have idiopathic
J AM ACAD DERMATOL Labib et al 1195
VOLUME 89, NUMBER 6

Table I. A summary of the clinical features and presentation of sensory abnormalities for the most common
central and peripheral etiologies of generalized dysesthesia
Central Diagnosis
Spinal cord injury
Stroke
Multiple sclerosis
Myelopathy
Encephalitis
Central nervous system tumors
Peripheral Radiculopathy
HSAN/CMT Disease
Diabetic peripheral neuropathy
HIV-associated peripheral
neuropathy
GuillaineBarre syndrome
Chemotherapy-related peripheral
neuropathy
Chronic alcohol consumption-
related peripheral neuropathy
Small fiber neuropathy
Clinical features
Paralysis at the site of injury,
fatigue and weakness, pain at
the site of injury
Sensory abnormalities, motor
weakness
Optic neuritis, muscle weakness
ataxia, Lhermitte’s Sign
Muscle weakness, abnormal
reflexes, loss of urinary or bowel
control, upper motor neuron
signs
Fever, altered consciousness,
memory deficits, aphasia,
seizures, neurological and
psychiatric signs
Headaches, blurred vision, lower
limb weakness, spinal pain,
autonomic dysfunction
Radiating pain, motor dysfunction
in the neck and extremities
Pes cavus, hammer toes,
progressive distal leg weakness,
atrophy, suppressed or absent
reflexes, injury in limbs, family
history
Foot ulcers, autonomic
dysfunction
Progressive weakness, foot or wrist
drop, facial weakness, focal pain
Muscle weakness, pain, urinary
retention, sinus tachycardia,
hypertension, cardiac
arrhythmia, and/or postural
hypotension
Muscle weakness
Impaired vibration sensation,
diminished/absent reflexes
Autonomic dysfunction
Dysesthesia presentation
Pain and numbness below the
spinal lesion
Variable presentation,
asymmetrical, unilateral
Paroxysmal dysesthesias, relapsing
and remitting
Numbness and tingling in the
hands and feet
Acute (infectious), subacute/
chronic (autoimmune)
Lower limb dysesthesia,
progressive, initially localized
Painful dysesthesias
Presents at a young age, chronic,
length-dependent
Burning, painful, length-
dependent, symmetric
‘‘Burning feet’’, distal and
symmetrical numbness of the
upper extremities (chronic)
Burning, tingling, or shock like
sensations, lower extremity,
symmetrical, length-dependent
Subacute, extreme sensitivity to
cold, allodynia,
length-dependent
Lower extremity, chronic
Chronic, slowly progressive,
length-dependent

CMT, Charcot-Marie-Tooth.

peripheral neuropathy; yet, small fiber neuropathy is EVALUATION

present and dysesthesia is a prominent symptom.89
Small fiber neuropathy, thought to be a potential
underlying mechanism of dysesthesia, is in and of
itself a diagnosis that can cause sensory phenom-
ena.50 Small fiber neuropathy occurs in many con-
ditions or can appear to be idiopathic.90 Typically,
dysesthesia in the setting of small fiber neuropathy is
length-dependent and slowly progressive.
The clinical presentation of generalized dysesthe-
sia can help stratify the differential diagnoses. A
thorough patient history that addresses time of onset,
distribution (length dependent, length independent,
or multifocal), change or progression of distribution,
frequency (intermittent or persistent), chronicity,
clinical modality (sensory, motor, autonomic, or
combination) as well additional symptoms, medical
1196 Labib et al J AM ACAD DERMATOL
DECEMBER 2023

Table II. Summary of the differential diagnoses and evaluation for generalized dysesthesia
Etiology Differential diagnoses Evaluation Special considerations
Central d Stroke Acute/Severe features / d Lumbar puncture
d Central poststroke syndrome d Neurological evaluation d Vitamin B12 evaluation
d Malignancy d Imaging (MRI/CT) d Myelography
d Radiculopathy d Cerebral angiography
d Myelopathy Sub-acute/Chronic / d Brain biopsy
d CBC
d Trauma
d CMP
d MS
d ESR, C-reactive protein
d Encephalitis
d Urine analysis
d Vasculitis
d B12 deficiency
Peripheral d Radiculopathy Acute/Subacute/Length d TSH
d HSAN independent/Multifocal/Severe d SPIEP
d CMT Disease features / d Vitamin B12 evaluation
d Diabetic PN d Neurological evaluation d ELISA (HIV, Lyme disease)
d Metabolic syndrome d EMG
d Viral infection (HIV, viral hepatitides, Chronic / d NCS
d CBC
herpes virus, coronavirus) d Skin biopsy
d CMP
d Bacterial infection (Lyme d Quantitative sensory
d ESR
disease, leprosy) testing 1 autonomic testing
d Fasting glucose/hemoglobin
d Guillain-Barr
e Syndrome d Nerve biopsy
d Sarcoidosis A1C
d Amyloidosis
d Vasculitis
d Dysproteinemias
d Sjogren’s syndrome
d Hypothyroidism
d Drug-induced PN (chemotherapies,
cardiovascular agents,
antibiotics, antiretrovirals)
d Chronic Alcoholism
d B6, B9, and B12 vitamin
deficiency
d Copper deficiency
d Post-viral exanthem
d Post-DRESS

CBC, Complete blood count; CMP, complete metabolic panel; CMT, Charcot-Marie-Tooth; DRESS, Drug Rash with Eosinophilia and Systemic
Symptoms; ELISA, enzyme-linked assay; EMG, electromyography; ESR, erythrocyte sedimentation rate; HSAN, Hereditary Sensory and
Autonomic Neuropathies; MRI, magnetic resonance imaging; NCS, nerve conduction studies; PN, peripheral neuropathy; SPIEP, serum protein
immunofixation electrophoresis; TSH, thyroid stimulating hormone.

history, social history, recent illness/rashes, and any
change in medication, is important to note.
Additionally, a neurologic-focused physical exam
can help assess the extent of neuropathy.91 Lastly, a
dermatologic physical exam, which may reveal
primary or secondary cutaneous findings, can also
help identify certain predisposing conditions.92
Evaluation of concerning features for CNS-related
pathologies, such as headache, episodes of
weakness, altered sense of consciousness, and focal
neurologic deficits, should prompt action such as
neurologic evaluation. The work-up should begin
with laboratory investigations, including a
complete blood count, complete metabolic panel,
inflammatory markers, and urine analysis. Imaging
via magnetic resonance imaging scans or computed
tomography scans is important in detecting
stroke,93,94 acute spinal injury,95 or inflammation.96
For cases of suspected encephalitis, lumbar puncture
in addition to imaging is employed to identify the
pathogen or rule out infection.96
For more chronic CNS-related pathologies, similar
blood work should be initiated as well as vitamin B12
evaluation. Imaging is usually the next step in a
calculated work-up; yet the modality and supporting
exams vary for different etiologies.97-100 The
diagnosis of MS can also be supported by the
presence of CSF oligoclonal bands.101 Imaging with
cerebral angiography, in addition to brain biopsy, is
the gold standard for vasculitis diagnosis, in addition
J AM ACAD DERMATOL
VOLUME 89, NUMBER 6
to magnetic resonance imaging and computed to-
mography scans.102
Peripheral neuropathy that is acute, subacute, or
rapidly progressive should be redirected to neuro-
logic consultation.103 Patients with additional find-
ings such as length independent distribution,
multifocal distribution, and significant motor or
autonomic dysfunction would also benefit from
specialty consultation. Additionally, severe features
such as gait ataxia and proprioceptive dysfunction in
patients with length-dependent sensory peripheral
neuropathy should also be guided to specialty
consultation.
For other presentations of peripheral neuropathy,
the first step is serological evaluation with a
complete blood count and comprehensive metabolic
panel with consideration to renal function, liver
function tests, erythrocyte sedimentation rate, fasting
glucose or hemoglobin A1C, thyroid stimulating
hormone, serum protein immunofixation electro-
phoresis, vitamin B12, and enzyme-linked assay for
Lyme disease and HIV.103 If the cause is still un-
known, then electromyography and nerve
conduction studies can confirm peripheral neurop-
athy and characterize the extent of pathology. If a
clear diagnosis is not established after electromyog-
raphy and nerve conduction studies testing, then
assessment for small nerve fiber function can be used
to follow-up on findings. Skin biopsy is the gold
standard diagnostic tool for small nerve fiber neu-
ropathy, consisting of a 3-millimeter punch biopsy in
the following regions: medial foreleg, thigh, shoul-
der.104 The specimen is analyzed with immunofluo-
rescence or immunohistochemistry to determine the
density of small nerve fibers.50 Lastly, nerve biopsy
(ie, sural nerve) can be a diagnostic tool to identify
chronic inflammatory, infectious, or infiltrative etiol-
ogies (Table II).103 Patients can be referred to
neurology if these evaluations are not within the
spectrum of care typically provided by the
dermatologist.
MANAGEMENT
Management should begin with treating the
underlying disease, as treating the condition can
halt the progression or resolve dysesthesia.
However, the pathologies that incite neurologic
damage have long-lasting effects and treatment is
symptom reduction.103
Symptomatic treatment of generalized dysesthesia
utilizes interventions that target the nervous system.
These include nonpharmacologic interventions and
pharmacologic agents. Frequent re-evaluation of
symptoms to monitor the underlying disease and
progression is recommended.105 A multidisciplinary
Labib et al 1197
approach, such as referral to rehabilitation,
occupational therapy, or physical therapy can be useful
for patients preferring less invasive measures or in
conjunction with medicinal treatment.105 However,
first-line treatments are pharmacologic agents.
First line pharmacologic treatments are anti-
convulsant therapies gabapentin and pregabalin,
tricyclic antidepressants, and serotonin noradrena-
line reuptake inhibitors.103,105,106 For peripheral
neuropathy, there are data that suggests that prega-
balin may be more effective than gabapentin.107
Alternative medications are capsaicin and lidocaine
patches. There is less evidence for the use of
tramadol, opioids, and sodium-channel blockers;
therefore, they are not recommended or reserved
for special cases.103,105,106 Treatments are increased
to achieve maximal success; however, complete
remission of symptoms is hard to accomplish, and
often combination therapy is needed. When
refractory to these therapies, the next intervention
is spinal cord stimulation or direct spinal drug
administration, although research suggests these
options yield limited efficacy.103,106,108
CONCLUSION
Generalized dysesthesia is a perplexing symp-
tom that is often encountered first among derma-
tologists. It is challenging to interpret the
presentation, deduce appropriate differential di-
agnoses, and provide the best follow-up measures
and treatments.
When approached with this symptom, stratifying
the presentation into CNS- or PNS- related pathology
can narrow down the diagnosis and effectively guide
clinicians. Recognizing the likely etiology is the most
important step, as treatment is best accomplished by
addressing the cause.103,105,106 However, the
complexity of generalized dysesthesia will
likely require a multidisciplinary approach of
management, including symptomatic treatment of
neuropathic symptoms.103,105,106
There is a need to establish useful guidelines that
can help dermatologists approach the care of
patients presenting with generalized dysesthesia as
there is no published literature that specifically
addresses this symptom. In this review, the
mechanism, clinical features, differential diagnoses,
evaluation, and management have been outlined
to facilitate the understanding of generalized
dysesthesia.
Conflicts of interest
None disclosed.
1198 Labib et al
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JAAD GAME CHANGER

JAAD Game Changer: ‘‘Primary dermal melanoma: A

unique subtype of melanoma to be distinguished from
cutaneous metastatic melanoma: A clinical, histologic,
and gene expression-profiling study’’
Robert T. Brodell, MD
Original Article Information: Sidiropoulos M, Obregon R, Cooper C, Sholl LM, Guitart J, Gerami P. Primary dermal
melanoma: A unique subtype of melanoma to be distinguished from cutaneous metastatic melanoma: A clinical, histologic,
and gene expression-profiling study. J Am Acad Dermatol. 2014;71:1083-1092. https://doi.org/10.1016/j.jaad.2014.07.051

How did this article change
the practice of dermatology?
d When patients present with a mid or deep dermal melanoma showing
no attachment to the epidermis, in the setting where there is no
known primary lesion and no other evidence of metastatic disease,
dermatologists should not jump to the conclusion that the lesion is
metastatic. It could be primary dermal melanoma.
d With complete excision, this condition has a much better prognosis
than metastatic malignant melanoma and gene expression profiling
(precisionDx-Melanoma (Castle Biosciences Inc) may be useful here
since primary dermal melanoma will likely show a Class 1 signature,
while metastatic melanoma usually shows a Class 2 signature.

Conflicts of interest: None disclosed.

Note: A Game Changer is a short narrative stating how an article

that originally appeared in JAAD changed the game of
dermatology. The Game Changer author is not the author of
the original article.
From the Dermatology, University of Mississippi Medical Center,
Jackson, Mississippi.
Funding sources: None.
IRB approval status: Not applicable.
Accepted for publication June 27, 2023.
Correspondence to: Robert T. Brodell, MD, Dermatology,
University of Mississippi Medical Center, 2500 North State St,
Jackson, MS 39216. E-mail: rbrodell@umc.edu.
Published by Elsevier Inc. on behalf of the American Academy of
Dermatology, Inc.
https://doi.org/10.1016/j.jaad.2023.08.023