Prurigo Nodularis

Article Author:
Tessa Mullins
Article Author (Archived):
Poonam Sharma
Article Editor:
Sidharth Sonthalia
Updated:
5/18/2019 7:59:09 PM
PubMed Link:
Prurigo Nodularis

Introduction

Prurigo nodularis is a chronic disorder of the skin that is classically seen as multiple, firm, flesh to pink colored nodules commonly located on the extensor surfaces of the extremities. The lesions are typically pruritic and can occur in any age group. It is commonly associated with another disease such as atopic dermatitis or chronic pruritus. The diagnosis is clinical. Antihistamines, behavioral changes, topical corticosteroids, intralesional corticosteroids, as well as systemic therapies for extreme cases, treat prurigo nodularis.[1][2][3][4]

Etiology

The etiology of prurigo nodularis is unknown. It is uncertain how the itch-scratch cycle plays a role and whether the lesions are present before the pruritus or the pruritus causes the lesions. The question of if inflammation and increased size of dermal nerves can play a role in the formation of prurigo nodularis remains under investigation.[5][6]

Epidemiology

The incidence of prurigo nodularis is unknown. It can be seen in all age groups, but most commonly, it is seen in older adults. The average age of onset of prurigo nodularis was 62 years There is no predilection of gender for prurigo nodularis as both sexes are equally affected. It is seen in patients with atopic dermatitis and can present earlier in patients with atopic dermatitis.[REFERENCE???] Prurigo nodularis has also been found in 5% of HIV patients with a cluster of differentiation (CD4+) count of less than 200.[REFERENCE???]

Pathophysiology

The pathophysiology of prurigo nodularis has been debated. Some studies have shown an increased number of nerves in the papillary dermis which may suggest a neurocutaneous component. Nerve growth factor (NGF) and its receptor, tyrosine receptor kinase A (TrkA), are overexpressed in prurigo nodularis lesions. They may also be associated with the increased release and accumulation of neuropeptides, such as substance P and calcitonin gene-related peptide[7]. The role of helper T cytokines, T helper 1 and T helper 2, have also been studied in the pathogenesis of prurigo nodularis using the signal transducers and activators of transcription (STAT) 1, 3, and 6. In every case examined but three, the entire epidermis stained with anti-pSTAT 6, a marker for the Th2 cytokines interleukin (IL)-4, IL-5, and IL-13. These findings suggest that Th2 cytokines play a principal role in the pathogenesis of prurigo nodularis. 

PLEASE ADD RELEVANT REFERENCES.........

Histopathology

Lesions of prurigo nodularis under histopathology can show thick, orthohyperkeratosis, irregular epidermal hyperplasia, and pseudoepitheliomatous hyperplasia. Focal parakeratosis with irregular acanthosis diminished nerve fiber density and a nonspecific dermal infiltrate containing lymphocytes, macrophages, eosinophils, and neutrophils may also be seen on histology for prurigo nodularis lesions. Histology can play an important role in diagnosing prurigo nodularis vs. lichen simplex and hypertrophic lichen planus. Lesions of lichen simplex are less likely to have pseudoepitheliomatous hyperplasia or nerve fiber thickening; however, it does not rule out the histological diagnosis of PN. It is necessary to correlate clinical and histological findings together to reliably distinguish between PN and LS[8]. HLP and PN both demonstrate epidermal hyperplasia, hypergranulosis, and compact hyperkeratosis. Vertically arranged collagen fibers and an increased number of fibroblasts and capillaries in the dermis are found in both conditions. However, basal cell degeneration is limited to the tips of rete ridges, and no band-like inflammation will be seen in HLP vs. PN

PLEASE ADD RELEVANT REFERENCES.........

History and Physical

Patients with prurigo nodularis present with a characteristic firm, dome-shaped, pruritic nodules that vary in size from a few millimeters to centimeters. The nodules can be flesh colored, erythematous, pink, and brown/black. Initially, the lesions can begin as normal skin or areas of xerosis. Due to pruritus, the patients will begin and continue to scratch the lesions until the dome shaped nodule forms. Typically, the lesions are found symmetrically on the patient’s extensor surfaces of the arm and legs. Lesions can also be found in the occipital region of the scalp. The upper back, abdomen, and sacrum also can be involved. Usually, areas that are difficult to reach such as the upper mid back are spared. This finding is called the “butterfly sign.” The palms, soles, face, and flexural areas are usually spared. There is associated severe pruritus that can be very distressing for the patients with prurigo nodularis. It can be sporadic or continuous and can increase with sweating, clothing irritation, or heat. It has been reported that in some cases, atopic dermatitis and xerosis are found in conjunction with prurigo nodularis and may be the initiating factor. Lesions can often appear excoriated due to the pruritus involved with PN. Excoriated lesions are at increased risk of secondary infection and can appear crusted, erythematous or painful if infected. 

I CAN ADD A CONSOLIDATED IMAGE FROM MY SIDE CONTAINING TYPICAL CLINICAL, DERMOSCOPIC AND HISTOLOGICAL IMAGES

Evaluation

Prurigo nodularis is a clinical diagnosis. Prurigo nodularis patients will likely have a history of chronic severe pruritus with excoriations and flesh-colored, pink nodular lesions on extensor surfaces. Dermoscopy can be a helpful tool when diagnosing PN vs. HLP. In one study, dermoscopy of HLP demonstrated pearly white areas and peripheral striations, gray-blue globules  comedo-like openings, red dots and globules, brownish-black globules and yellowish structures. In PN, red dots and globules and pearly white areas with peripheral striations were observed under dermoscopy[9]. Skin biopsy may be warranted for lesions that are bleeding, have formed ulcers or are resistant to first-line therapies. If patients with prurigo nodularis and severe pruritus do not have a cause of the pruritus, causes of chronic pruritus should be evaluated. Causes of severe pruritus can include renal disease, liver disease, thyroid disease, HIV infection, malignancy or parasitic infection. Evaluation of these causes includes a complete blood cell count (CBC), complete metabolic panel, thyroid studies including TSH and free T4, urinalysis, stool exam, HIV antibodies and chest x-ray. Serum IgE levels can also be elevated in patients with PN and atopic dermatitis.

PLEASE ADD RELEVANT REFERENCES.........

Treatment / Management

Management of prurigo nodularis requires a multifaceted approach. Patients need to be educated on practices to reduce scratching of lesions, assurance and diagnosing of underlying causes of pruritus and diagnosis and treatment of any psychological disorder associated with scratching and picking at skin. Treatments, both topical and systemic, are targeted at disrupting the itch-scratch cycle.

General Care

  • Patients are encouraged to keep their nails short, wear protective clothing such as long sleeves and gloves, and to keep the nodules covered with bandages. 
  • Using gentle cleansers to bathe and applying emollients multiple times a day to keep skin moisturized should be encouraged.
  • Calamine lotions and lotions containing menthol and camphor can provide relief from the pruritus.

Systemic Therapy

  • First-generation sedating antihistamines such as hydroxyzine administered at bedtime may be useful in controlling nocturnal pruritus at doses up to 25 mg. Common adverse reactions to antihistamines are drowsiness, dizziness and weakness. 
  • Both selective serotonin reuptake inhibitors and tricyclic antidepressants can also be considered for chronic pruritus. It is important for patients to also be seen in conjunction with a mental health professional. 
  • Thalidomide, lenalidomide, immunosuppressants such as cyclosporine and methotrexate, and anticonvulsants have all been systemic therapies tried on patients with prurigo nodularis. As with topical therapies, no randomized trials have been reported involving the use of these systemic therapies and the benefits versus risks of the drugs must be considered before beginning treatment[10]

Topical Therapy

  • Although none have been examined in randomized trials, topical treatments for prurigo nodularis include class one topical corticosteroids, intralesional corticosteroids, topical calcineurin inhibitors, topical capsaicin, and topical vitamin D analogues.
  • First line therapy is suggested to be topical corticosteroids, such as clobetasol dipropionate 0.05% ointment applied under occlusion with plastic wrap once at nighttime for at least two to four weeks.
  • Acetonide in concentrations of 10 mg/mL to 20 mg/mL injected intralesionally has been shown to flatten lesions and provide relief from pruritus. [11][12][13][14][15]

Phototherapy

  • Phototherapy with PUVA, including bath/topical PUVA, long-wavelength ultraviolet A, narrowband ultraviolet B, and monochromatic excimer light of 308 nm, have been used and shown improvement of prurigo nodularis nodules in patients.

Differential Diagnosis

Lichen simplex chronicus 

Hypertrophic lichen planus

Pemphigoid nodularis

Nodular scabies

Keloids

Dermatofibroma

Foreign body reactions

Treatment Planning

First Line

  • Class 1 topical steroids
  • Intralesional injections 
  • Topical menthol solutions

Second line

  • Systemic antihistamines

THE DOSES AND FEW LIMITING ADVERSE EFFECTS OF ALL DRUGS CAN ALSO BE MENTIONED HERE

Prognosis

Prurigo nodularis is a benign condition with a good prognosis.  

Complications

Lesions of prurigo nodularis can become secondarily infected due to scratching of the lesions. It is important to monitor for clinical signs of infection such as erythema, pain, warmth and fever. If secondary infection is suspected, it is important to begin appropriate topical or systemic antibiotic therapy to cover for skin flora. 

Pearls and Other Issues

Prurigo nodularis is a chronic skin disease that can cause a significant impact on a patients quality of life. Breaking the itch-scratch cycle requires a multifaceted approach and patients should be encouraged to continue with therapy to reduce scratching and picking at the lesions. It may be necessary to involve behavioral therapy if required. It is important to explain to patients that prurigo nodularis lesions may be chronic and very difficult to improve completely.

Enhancing Healthcare Team Outcomes

Management of prurigo nodularis requires a multidisciplinary team that includes the primary caregiver, nurse practitioner, dermatologist and a mental health nurse. Patients need to be educated on practices to reduce scratching of lesions, assurance and diagnosing of underlying causes of pruritus and diagnosis and treatment of any psychological disorder associated with scratching and picking at skin. Treatments, both topical and systemic, are targeted at disrupting the itch-scratch cycle. Patients are encouraged to keep their nails short, wear protective clothing such as long sleeves and gloves, and to keep the nodules covered with bandages. Using gentle cleansers to bathe and applying emollients multiple times a day to keep skin moisturized should be encouraged. Calamine lotions and lotions containing menthol and camphor-like Sarna can provide relief from the pruritus. First-generation sedating antihistamines such as hydroxyzine administered at bedtime may be useful in controlling nocturnal pruritus. Both selective serotonin reuptake inhibitors and tricyclic antidepressants can also be considered for chronic pruritus. [16]

Finally, the pharmacist should educate the patient on potential adverse reactions of the medications.


References

[1] Harbaoui S,Litaiem N, Acquired Perforating Dermatosis 2019 Jan;     [PubMed PMID: 30969537]
[2] Larson VA,Tang O,Stander S,Miller LS,Kang S,Kwatra SG, Association between prurigo nodularis and malignancy in middle-aged adults. Journal of the American Academy of Dermatology. 2019 Apr 4;     [PubMed PMID: 30954580]
[3] Ständer S,Kwon P,Hirman J,Perlman AJ,Weisshaar E,Metz M,Luger TA, Serlopitant reduced pruritus in patients with prurigo nodularis in a phase 2, randomized, placebo-controlled trial. Journal of the American Academy of Dermatology. 2019 Mar 17;     [PubMed PMID: 30894279]
[4] Kowalski EH,Kneiber D,Valdebran M,Patel U,Amber KT, Treatment-resistant prurigo nodularis: challenges and solutions. Clinical, cosmetic and investigational dermatology. 2019;     [PubMed PMID: 30881076]
[5] Lee S,Wang HY,Kim E,Hwang HJ,Choi E,Lee H,Choi EH, Clinical characteristics and genetic variation in atopic dermatitis patients with and without allergic contact dermatitis. European journal of dermatology : EJD. 2018 Oct 1;     [PubMed PMID: 30530433]
[6] Krammer CW,Ibrahim RM, Prurigo Nodularis after Radiotherapy: An Isoradiotopic Response? Case reports in dermatological medicine. 2018;     [PubMed PMID: 30245894]
[7] Lee MR,Shumack S, Prurigo nodularis: a review. The Australasian journal of dermatology. 2005 Nov     [PubMed PMID: 16197418]
[8] Weigelt N,Metze D,Ständer S, Prurigo nodularis: systematic analysis of 58 histological criteria in 136 patients. Journal of cutaneous pathology. 2010 May     [PubMed PMID: 20002240]
[9] Nair PA,Patel T, Dermatoscopic Features of Prurigo Nodularis. Indian dermatology online journal. 2019 Mar-Apr     [PubMed PMID: 30984602]
[10]     [PubMed PMID: 23767411]
[11] Katayama C,Hayashida Y,Sugiyama S,Shiohara T,Aoyama Y, Corticosteroid-resistant prurigo nodularis: a rare syringotropic variant associated with hypohidrosis. European journal of dermatology : EJD. 2019 Mar 2;     [PubMed PMID: 30827950]
[12] Legat FJ, The Antipruritic Effect of Phototherapy. Frontiers in medicine. 2018;     [PubMed PMID: 30560129]
[13] Gupta MA,Pur DR,Vujcic B,Gupta AK, Use of antiepileptic mood stabilizers in dermatology. Clinics in dermatology. 2018 Nov - Dec;     [PubMed PMID: 30446200]
[14] Beck KM,Yang EJ,Sekhon S,Bhutani T,Liao W, Dupilumab Treatment for Generalized Prurigo Nodularis. JAMA dermatology. 2019 Jan 1;     [PubMed PMID: 30427994]
[15] Qureshi AA,Abate LE,Yosipovitch G,Friedman AJ, A systematic review of evidence-based treatments for prurigo nodularis. Journal of the American Academy of Dermatology. 2019 Mar;     [PubMed PMID: 30261199]
[16] Boozalis E,Tang O,Patel S,Semenov YR,Pereira MP,Stander S,Kang S,Kwatra SG, Ethnic differences and comorbidities of 909 prurigo nodularis patients. Journal of the American Academy of Dermatology. 2018 Oct;     [PubMed PMID: 29733939]