What Caused This Refractory Unilateral Pruritic Hyperpigmented Eruption?

A 29-year-old otherwise healthy Asian woman presented with refractory and debilitating bouts of itching limited to the right lateral knee (Figure 1), right lower leg, and right dorsal foot (Figure 2) for more than 5 years’ duration. She had seen multiple dermatologists for resultant right leg prurigo nodules, hyperpigmentation, lichenification, and more than 40 to 50 raised, rough, wart-like papules. Her left leg was completely clear and the remainder of the physical exam was unremarkable. One dermatopathology report of a biopsy of the right knee dated 3 years prior noted papulosquamous dermatitis, lichenified with no evidence of psoriasis. 

Examination of the low back confirmed moderate spinal tenderness over the fourth lumbar through first sacral vertebrae that was associated with bilateral muscle spasm, particularly of the left side. Pertinent history included a motor vehicle accident several years prior and periods of extended daily driving for work. Patient denied debility or pain in the neck or back. 

She had failed to improve despite numerous past therapies, including potent topical and intralesional steroids, phototherapy with narrowband UV-B, steroid-impregnated tape, and oral and topical antihistamines.

What Is Your Diagnosis?
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Diagnosis: Atypical Spinal Lumbar Paresthetica Associated With L4-S1 Severe Disc Disease in a Young Woman With a Newly Diagnosed Autoimmune Disorder 

Spinal paresthesias, or spinal paresthetica, are neurocutaneous disorders that embody skin-itch-spine syndromes (SISS), including notalgia paresthetica (NP), brachioradial pruritus (BRP), and meralgia paresthetica (MP). These pruritic conditions are heavily underrecognized and underdiagnosed causes of episodic and chronic localized dysesthesias and itching of the midback, upper extremities, and lateral thighs, respectively.^1-7While NP and BRP are often described as independent conditions, these two conditions do often occur concurrently or serially in the same individual.^1,2 Similarly, the described L4-S1 paresthesias are not uncommon and do frequently occur contiguously or subsequently in the same patients with NP and BRP (HB Skinner, MD, PhD; oral communication, January 2019). 

The term paresthesia describes the burning or prickling sensation usually felt in the hands, arms, legs, or feet, but these sensations can also occur in other parts of the body.⁸ The sensation, which happens without warning, is usually painless and described as tingling or numbness, skin crawling, or itching. Spinal paresthesias such as NP and BRP may in fact represent the same spectrum of one pathophysiologic neuropathic disorder originating from the cervical spine, whereas the condition described herein originates from the lumbosacral spine.^1-7

The fourth through sixth cervical vertebrae as well as the fourth lumbar through first sacral vertebrae are the two most injury- and degenerative disease-prone segments of the human spine. Conversely, the thoracic spine is largely stabilized by ribs and thus much less prone to injury (with the exception of compression fractures). This “weakest link” concept has been postulated by this author and others due to the potential premature evolution of Homo erectus (meaning upright man). Thus, it likely follows that while the erect human position has given humans tremendous advantages, the relative instability of the cervical and lumbar spine has also resulted in significant disease, likely including spinal paresthesias (HB Skinner, MD, PhD; written communication, January 2020).

Treatment 
A timely paradigm shift in the dermatologist’s recognition of the continuum of spinal paresthesias or SISS, including NP, BRP, and MP, as neurocutaneous disorders as well as a substantially redirected treatment approach to these conditions is warranted. The dermatologist’s focus should be placed on eliciting relevant spinal history, including cervical or lumbar muscle spasm, trauma, arthritis, degenerative disk disease, and other spinal neoplasms, and referring for treatment.^1,2,6,7,9

Topical therapies for SISS including NP and BRP have been highly inconsistent and nearly entirely unsatisfactory in a majority of patients.^1-3,9 Thus, treatment should be aimed at the spine, not the skin. Further, appropriate patient education for nearly all spinal paresthesias requires discussion of potential spinal conditions and clear awareness of the probable association of the localized itching with underlying spinal and musculoskeletal disease. 

Radiographic studies of the spine, including plain film and magnetic resonance imaging (MRI), should be considered in primary evaluation of refractory spinal paresthesias (SISS), including NP, BRP, and MP, more frequently than current standards. 

First-line therapy for spinal paresthesias with associated spinal disc disease should include consideration of potential nondermatologic therapies aimed at the spine.^1,2,6,7,9 Such spinal treatments include transcutaneous electrical stimulation (TENS), electrical muscle stimulation (EMS), acupuncture, infrared phototherapy, physical therapy, myofascial massage, muscle strengthening and range of motion enhancing routines, passive continuous motion, alternating heat and ice modalities, gentle spinal traction, mild spinal manipulation, oral nonsteroidal anti-inflammatory medications, and oral and topical muscle relaxants as required for resistant disease.^1,2,5-7,9,10

Prognosis and Disease Management 
Similar to prognostication of standard cervical or lumbar musculoskeletal diseases, spinal paresthesia conditions, including NP, BRP, and MP, are generally chronic, controllable conditions with periodic remissions and exacerbations. Collaborative multispecialty evaluation by dermatology, radiology, neurology, pain management, acupuncture, physical therapy, and orthopedic surgery may be indicated for best practices of management of these very common, albeit heavily underdiagnosed, unrecognized, and mistreated, conditions.^1,2

Our Patient
Our patient had seen no less than seven prior dermatologists over nearly as many years, and she reported failed treatments with flurandrenolide tape, intralesional triamcinolone, more than 30 sessions of phototherapy, potent topical steroids, and oral antihistamines.

On the patient’s first visit, based on clinical acumen of a unilateral dermatomal eruption and a provisional diagnosis of atypical low spine NP/MP (Figures 1 and 2), the following workup was efficiently undertaken. A spinal MRI demonstrated a L5-S1 tear of the posterior annulus fibrous, with a 4.5-mm central disc protrusion, compression of the traversing S1 nerve roots, and moderate to severe stenosis, as well as a L4-L5 tear, with a 5-mm broad-based left paracentral disc protrusion and severe stenosis with questionable compression of the traversing left L5 nerve roots (Figure 3).

Laboratory evaluation included a battery of pruritus serology tests, which demonstrated multiple newly diagnosed autoantibodies, leading to a rheumatologic referral. A novel multimodal therapy program, consisting of TENS and EMS, acupuncture, narrowband UV-B phototherapy, physical therapy, infrared phototherapy, oral hydroxyzine for breakthrough pruritus, and intralesional cortisone for any refractory prurigo nodules, was prescribed. This combination therapy resulted in near complete clearance of symptoms and cutaneous lesions at the second month (Figures 4 and 5).

Anatomy
Figure 6 depicts the anatomic rationale for the diagnosis and treatment of our patient based on the identification of the appropriate nerve root and corresponding affected dermatomes.¹¹ This figure¹¹ illustrates spinal dermatomes of the L4-S1 spinal nerves extending to the medial knee, medial calf, and dorsal medial midfoot as shown in the preceding figures. 

Conclusion 
The striking association of spinal paresthesias or SISS with degenerative, traumatic, or muscle-tension cervicolumbar spine disease suggests that spinal arthropathy or myalgia often contribute to the pathogenesis of the skin symptoms of NP, BRP, and MP.^1-5 These localized pruritus conditions affect all ages from young adults to the elderly. Thus, a timely paradigm shift in the dermatologist’s global assessment and approach to these diseases with therapies aimed at the spine, most commonly the fifth through sixth cervical vertebrae and the fourth lumbar through first sacral vertebrae is deemed necessary.^1-3 This highlights the author’s pearl of “treat the spine, and the skin will follow”.

Note: Spinal paresthesia, spinal paresthetica, and SISS are three new terms coined by this author and can be used interchangeably to encompass the continuum of spinal diseases including NP, BRP, MP, burning scrotum syndrome, and burning scalp.

Dr Alai is the medical director at The Skin & Wellness Center in Laguna Hills, CA, and a former associate professor at the University of California, Irvine.

Disclosure: The author reports no relevant financial relationships.  

References
1. Alai NN, Skinner HB, Nabili ST, Jeffes E, Shahrokni S, Saemi AM. Notalgia paresthetica associated with cervical spinal stenosis and cervicothoracic disk disease at C4 through C7. Cutis. 2010;85(2):77-81. 

2. Alai NN, Skinner HB. Concurrent notalgia paresthetica and brachioradial pruritus associated with cervical degenerative disc disease. Cutis. 2018;102(3):185-186, 189-190.

3. Goodkin R, Wingard E, Bernhard JD. Brachioradial pruritus: cervical spine disease and neurogenic/neuropathic pruritus. J Am Acad Dermatol. 2003;48(4):521-524. doi:10.1067/mjd.2003.203 

4. Şavk E, Şavk ŞÖ. On brachioradial pruritus and notalgia paresthetica. J Am Acad Dermatol. 2004;50(5):800-801. doi:10.1016/j.jaad.2003.07.022

5. Şavk E, Şavk Ö, Bolukbasi O, et al. Notalgia paresthetica: a study on pathogenesis. Int J Dermatol. 2000;39(10):754-759. doi:10.1046/j.1365-4362.2000.00080.x

6. Alai AN. Notalgia paresthetica. Medscape. https://emedicine.medscape.com/article/1599159-overview. Published July 10, 2018. Accessed January 3, 2020.

7. Dehghanian PM, Alai NN. What caused this refractory pruritic eruption? The Dermatologist. 2016;24(9):47-50.  

8. Paresthesia information page. National Institute of Neurological Disorders. https://www.ninds.nih.gov/Disorders/All-Disorders/Paresthesia-Information-Page. Published June 14, 2018. Accessed January 3, 2020.

9. Şavk E, Şavk Ö, Sendur F. Transcutaneous electrical nerve stimulation offers partial relief in notalgia paresthetica patients with a relevant spinal pathology. J Dermatol. 2007;34(5):315-319. doi:10.1111/j.1346-8138.2007.00279.x

10. Thornsberry LA, English JC 3rd. Scalp dysesthesia related to cervical spine disease. JAMA Dermatol. 2013;149(2):200-203. doi:10.1001/jamadermatol.2013.914

11. File: Grant 1962 663.png. Wikimedia Commons. https://commons.wikimedia.org/w/index.php?curid=30017222. Published December 5, 2013. Accessed January 6, 2020.