Severe, unremitting pruritus is the most characteristic features of this condition. Itching starts at a specific site and nodules form with repeated scratching and itching. These nodules are dark in color and do not change in size and generally increase in number. History of the patient may show renal abnormalities, trauma to skin, infection, HIV, or a psychiatric condition [8]. Patient usually depends on multiple medications, both oral and topical, for controlling the pruritus, but without much relief. Most of the patients have a family history of conditions like atopic dermatitis, hay fever, or asthma.

Nodules are usually 20 mm in diameter and scaly in appearance. The lesions are hyperpigmented and firm. They usually appear on the extensor surface of arms, legs, and trunk. Face, palms and soles are rarely affected by nodules. The nodules may be crusted, flat or umbilicated. Nodules are symmetrically distributed and the intervening skin also may be hyperpigmented. Some of the earlier lesions are erythematous. The color later changes to grey or red-grey. Many of them may develop bloody debris. In very few cases bacterial superinfection can be seen. Persistent form of these nodules may develop into anetoderma. The skin in these region may lose elasticity and show soft depression on the surface.

• Malaise

  Mild adverse effects at this point included nausea, vomiting, malaise, and arthralgias, which improved upon decreasing her dose to every other night. [jddonline.com]

• Falling

  Report begins with the market definition and explaining different product types which fall und prurigo nodularis treatment. [futuremarketinsights.com]

• Pruritus

  A 50-year-old gypsy woman presented with intense pruritus and skin lesions. She had controlled hypertension and Stage-4 chronic kidney disease with no hyperparathyroidism. No cholestatic disorder was observed. [academic.oup.com]

  CONCLUSION: Similar to the situation in PN, chronic pruritus lesions also demonstrate a preponderance of SP+ sensory nerve fibers relative to sympathetic nerve fibers, which probably acts as a causal pro-inflammatory signal in development of pruritus. [ncbi.nlm.nih.gov]

• Dermatitis

  Type 2 Excludes chronic (childhood) granulomatous disease ( D71 ) dermatitis gangrenosa ( L08.0 ) dermatitis herpetiformis ( L13.0 ) dry skin dermatitis ( L85.3 ) factitial dermatitis ( L98.1 ) perioral dermatitis ( L71.0 ) radiation-related disorders [icd10data.com]

  After considering and excluding other differential diagnoses, the diagnosis of prurigo nodularis (PN) in association with atopic dermatitis was made. [ncbi.nlm.nih.gov]

  The differential diagnosis for PN includes dermatitis herpetiformis, scabies, lichen simplex chronicus, hypertrophic lichen planus, perforating disorders, atopic dermatitis, allergic contact dermatitis, neurotic excoriations, and multiple keratoacanthomas [mdedge.com]

  "Role of bacterial pathogens in atopic dermatitis". Clinical Reviews in Allergy & Immunology. 33 (3): 167–177. doi:10.1007/s12016-007-0044-5. PMID 18163223. [en.wikipedia.org]

• Papule

  It occurs in patients with chronic itch and is characterized by multiple hyperkeratotic papules and nodules. The pathogenesis of PN is unclear, but involves a complex interplay of numerous pathways including neurogenic and inflammatory factors. [jhu.pure.elsevier.com]

• Skin Disease

  We studied some cases of Hide's Prurigo Nodularis (NP), a very itchy skin disease of unknown origin, in order to asses whether there is a pathogenic correlation between PN and H. pylori infection. [ncbi.nlm.nih.gov]

  The middle-aged to elderly persons are often the persons affected by this kind of skin disease. It is a chronic kind of inflammatory dermatosis or skin disease that results to papulonodular eruption. [ehealthwall.com]

  The Impact of Skin Disease on Daily Life (ISDL) questionnaire, [5] a tool validated for use as a multidimensional health status inventory for chronic skin diseases, was used. [e-ijd.org]

• Skin Lesion

  Prurigo nodularis is a dermatosis originating from pruritus and the persistence and progression of skin lesions are strictly correlated to scratching and rubbing. The skin between the lesions is usually normal but can be xerotic or lichenified. [academic.oup.com]

  For the first time, culture and PCR analysis of skin biopsy confirmed the presence of Mycobacterium tuberculosis complex in PN skin lesions. The pruritus and skin lesions resolved following antitubercular therapy. [ncbi.nlm.nih.gov]

• Anxiety Disorder

  The individual diagnoses were along expected lines in that depressive and anxiety disorders were the most common. [idoj.in]

  In addition, anxiety disorders, depressions, and tactile hallucinations can also lead to chronic pruritus and thereby to PN as well 26. Treatment of prurigo nodularis PN requires a multimodal itch therapy based on mainly two arms. [journals.lww.com]

• Kidney Failure

  Volume 31, Issue 2 （February 2015） 臨牀透析 31巻2号 （2015年2月） 合併症の観察ポイントと専門医へのコンサルトのタイミング 皮膚科　そう痒症への対策 鈴木 洋通 1 1 埼玉医科大学 腎臓内科 キーワード： 血液透析, 腎不全-慢性, そう痒症, 理学療法, スキンケア, 摩擦, 皮膚保湿剤 Keyword: Kidney Failure, Chronic, Renal Dialysis, Pruritus, Friction, Skin Care, Physical [webview.isho.jp]

  This disease is often associated with internal diseases such as kidney failure, anemia due to iron deficiency, or metabolic disease such as intolerance to protein (called as gluten enteropathy), and many other diverse conditions such as HIV infection, [askdrshah.com]

  It also sometimes affects people who have certain underlying diseases, including kidney failure, HIV or hepatitis C infection, certain bacterial and parasitic infections, thyroid disease, lymphoma, and liver disease. [medicine.yale.edu]

  kidney failure, and psychiatric illnesses have been considered to induce PN, although more recent research has refuted a psychiatric cause for PN. [en.wikipedia.org]

Complete blood count (CBC) and other laboratory studies like liver function test are conducted to examine for underlying conditions like renal failure, hepatic diseases, or hematologic malignancies. Skin biopsy of nodules is used for culture and histologic examinations. These help to rule out squamous cells carcinoma and infections like mycobacterium. If dermatitis is seen in association with prurigo nodularis, patch sensitivity test is recommended. Histologic examination shows hyperkeratotic epidermis with acanthosis [9]. Cells like histiocytes, neutrophils, eosinophils and monocytes form a dense infiltrate in the dermis [10]. Thick bundles of collagen, nerve fibers and fibrosis are also characteristic of dermis. Increased proliferation of axons and Schwann cells is also noted. Some of the characteristic features of the cells include:

• Orthohyperkeratosis
• Irregular epidermal hyperplasia
• Pseudoepitheliomatous hyperplasia
• Superficial epithelial necrosis
• Hypergranulosis
• Papillary dermal fibrosis
• Hyperproliferation of fibroblasts
• Hyperproliferation of capillaries
• Inflammatory infiltrate of lymphocytes in interstitial region

Both clinical and histologic findings help to distinguish prurigo nodularis from lichen simplex chronicus [11]. In some patients the two conditions may coexist and result in nodules due to repetitive scratching or itching.

• Staphylococcus Aureus

  Staphylococcus aureus infection is related to the pathogenesis of eczema and AD. An antibiotic–corticosteroid combination and corticosteroid alone both gave good therapeutic effect in eczema and in AD, and both reduced colonization by S. aureus. [dx.doi.org]

Multiple treatment modalities are used at the same time to give effective control of symptoms. Most of the available treatments give only moderate relief. Medications focus on breaking the itching and scratching of affected region. Antipruritics are used to control itching by blocking the impulse. Inflammation and itching can be relieved using oral, topical, or intralesional corticosteroids. Intralesional corticosteroids are usually recommended for resistant forms of prurigo nodularis. Triamcinolone is found to be effective in most of the cases. For more scarred form of pruriginous lesions, higher concentration of triamcinolone is used. Topical agents like menthol, phenol, pramoxine, and vitamin D-3 ointment are also used for reducing pruritus. For severe form of pruritus, UV light treatment is also suggested. Topical capsacin makes the skin insensitive to pain by controlling peripheral sensory neurons.

Apart from steroids, antihistamines, anxiolytics, opiate receptor antagonists and thalidomide are the other oral medications suggested for controlling this condition. Antihistamines control itching by blocking histamine and are more useful during night. Thalidomide is recommended for prurigo nodularis associated with HIV. Topical immunomodulators may be useful in patients who are not responsive to steroids.

Cryotherapy is another method to flatten lesions and reduce pruritus [12]. This modality is particularly useful in case of lesions in upper limb and trunk in case of patients with diabetes and hypertension. This helps to minimize the adverse effects of corticosteroids. In this method, 2-4 treatment cycles are recommended. The number of cycles usually depends on the size of lesion. It is associated with scarring and pigmentation. In many cases, cryotherapy is combined with many other treatment modalities for better effect. Intralesional corticosteroids is one of the modalities used in combination. Vascularity of lesions are controlled by pulsed dye laser therapy.

Care should be taken about history of immune compromise and internal diseases, if any. Further investigation and examination is recommended in case of other associated diseases. Psychiatric consultation may be required in some cases, if underlying diseases are excluded. Patients should try to minimize itching and touching the nodules as much as possible.

Prurigo nodularis is a highly resistant form of dermatologic condition and a complete resolution of the nodules is rare. Spontaneous remission of prurigo nodularis has a poor outcome. Even after the completion of treatment, most of the nodules may remain. Control of itching and scratching may take long time, so as to give time for the nodules to resolve on its own. Prognosis is good with long-term treatment of the condition. The symptoms of the condition may keep changing, causing the patient to opt for alternative therapies and diagnostic procedures.

The actual cause of prurigo nodularis is unclear. It is found to be associated with a number of other conditions, but their role in causing or aiding in the development of prurigo nodularis is not known. In neural hyperplasia and certain types of inflammatory cells, prurigo nodularis shows distinct changes in nodules. Levels of mast cells and neutrophils are elevated with this condition. Although eosinophils are not increased, eosinophil cationic protein shows an elevated rate. Prurigo nodularis is found to be associated with increased number of papillary dermal cells and Merkel cells [2]. Presence of these cells differentiate pruritic nodules from lichen simplex chronicus. Substance P immunoreactive nerves and calcitonin gene-related peptide are also in increased levels in this condition [3]. These neuropeptides are implicated in the development of pruritus and inflammation. Infectious etiologies of prurigo nodularis include hepatitis C, mycobacteria, Helicobacter pylori, Strongyloides stercoralis, and HIV [4] [5]. This dermatologic condition is also associated with higher levels of interleukin 31.

Women are thought to be more affected by this condition, but there is no strong supporting evidence for the same. Racial predilections in the development of these nodules are also not known. Although it may develop in any age group, it is more common among middle-aged and old persons.

Thickening of the skin in nodules is caused by mechanical trauma. Thickness of the skin in the lesion is often proportionate to the extent of trauma. Patients with this condition resort to repetitive itching and scratching which leads to lichenification and hyperkeratosis. The repetitive scratching may also result in pigmentation of the skin in the affected region. Patients have an intense urge to scratch the area and it is often difficult to control the itching. Surface of the lesions gradually becomes crusted, and scaly. It is not clear whether dermal nerves play an important role in triggering pruritus. Proteinases and eosinophilic granules are implicated in the development of pruritus. One of the studies report that Th2 cytokine produced by the activation of STAT6 play an important role in the pathogenesis of pruritus [6]. Skin biopsy of the affected region show the presence of subclinical small fiber neuropathy in this condition [7].

Preventive measures of prurigo nodularis are not known.

Prurigo nodularis is a chronic skin condition characterized by discrete, persistent pruritic nodules on the dorsal extremities. First described by Hyde and Montgomery in 1909, prurigo nodularis has an unknown etiology [1]. It can develop into a debilitating condition in some patients. Prurigo nodularis may also develop secondary to many skin conditions like atopic dermatitis, and xerosis. It may also be induced by systemic conditions like internal malignancy and renal anomalies. Prurigo nodularis may occur in any age group is more common among middle-aged women. It often has a long course and may lead to significant stress and depression among patients. The nodules are usually grouped and symmetrically distributed. The nodules may itch continuously and the condition is one of the most resistant dermatologic conditions.

Prurigo nodularis is a skin condition characterized by itchy nodules in the arms and legs. Continuous scratching may cause crusted lesions. The condition is often very difficult to treat successfully. This inflammatory disease is of unknown origin. Repetitive scratching of the skin leads to the eruption of lesions with scaly surface. Induced by scratching the nodules may gradually thicken and become scaly in appearance. The nodules are mostly seen in the arms and legs, and very rarely on face, palm and soles. This skin disease is a very common condition, particularly among those who have associated diseases like atopic dermatitis or xerosis. Prevalence of this condition in the general population is not known. It is more commonly seen in middle-aged and old people. It is one of the most common skin conditions affecting people with HIV and indicates immunosuppression.

A nodule is about half an inch in diameter and dry and rough. It is often scratched open with bloody debris. Old dry scars may be noted next to old sores. Arms, shoulders and legs are mostly affected by nodules. It may be few or in groups of dozens. Presence of nodules causes scratching and this thickens the nerves in the skin. Thickening of skin nerves further induces scratching, resulting in a scratch cycle. Prurigo nodules is associated with many other diseases like kidney troubles, liver issues, and skin disease like eczema, and dermatitis. Many patients show anxiety regarding the presence of nodules and continuous itching. The number of nodules tend to increase with time. The nodules may not change size and they often do not resolve spontaneously.

Blood tests are used to test for underlying conditions like diseases of kidney, liver, or metabolic illness. Biopsy of tissue will help to check out for other diseases like mycobacterial infections, squamous cell carcinoma and fungal infections. Other diagnostic test include patch sensitivity test on affected skin. In most of the cases combination therapy is found to be more effective than single treatment modality. Some of the local treatments include emollients, anesthetic creams, capsaicin cream, and coal tar ointment, to reduce itching and to soothe the skin on nodules. Nodules are shrunk using cryotherapy. Itching can be controlled by antihistamines. Thalidomide is also effective in severe cases of pruritis. Other strategies include UV treatment and immunomodulators. Lesions of prurigo nodularis may not resolve spontaneously. Severity of the condition may be reduced through treatment. Complete cure can be obtained only by breaking the itch cycle, which is very hard to achieve.

1. Hyde JN, Montgomery FH. A practical treatise on disease of the skin for the use of students and practitioners. 1909;174-175.
2. Nahass GT, Penneys NS. Merkel cells and prurigo nodularis. J Am Acad Dermatol. 1994;31(1):86-88.
3. Vaalasti A, Suomalainen H, Rechardt L. Calcitonin gene-related peptide immunoreactivity in prurigo nodularis: a comparative study with neurodermatitis circumscripta. Br J Dermatol. 1989; 120(5):619-623.
4. Mattila JO, Vornanen M, Vaara J, Katila ML. Mycobacteria in prurigo nodularis: the cause or a consequence?. J Am Acad Dermatol. 1996;34(2 Pt 1):224-228.
5. Jacob CI, Patten SF. Strongyloides stercoralis infection presenting as generalized prurigo nodularis and lichen simplex chronicus. J Am Acad Dermatol. 1999;41(2 Pt 2):357-61.
6. Fukushi S, Yamasaki K, Aiba S. Nuclear localization of activated STAT6 and STAT3 in epidermis of prurigo nodularis. Br J Dermatol. 2011;165(5):990-996.
7. Schuhknecht B, Marziniak M, Wissel A, Phan NQ, Pappai D, Dangelmaier J, et al. Reduced intraepidermal nerve fibre density in lesional and nonlesional prurigo nodularis skin as a potential sign of subclinical cutaneous neuropathy. Br J Dermatol. 2011;165(1):85-91.
8. Matthews SN, Cockerell CJ. Prurigo nodularis in HIV-infected individuals. Int J Dermatol. 1998;37(6):401-409.
9. Feuerman EJ, Sandbank M. Prurigo nodularis. Histological and electron microscopical study. Arch Dermatol. 1975;111(11):1472-7.
10. Perez GL, Peters MS, Reda AM, Butterfield JH, Peterson EA, Leiferman KM. Mast cells, neutrophils, and eosinophils in prurigo nodularis. Arch Dermatol. 1993;129(7):861-5.
11. Weigelt N, Metze D, Ständer S. Prurigo nodularis: systematic analysis of 58 histological criteria in 136 patients. J Cutan Pathol. 2009;37(5):578-586. 
12. Stoll DM, Fields JP, King LE Jr. Treatment of prurigo nodularis: use of cryosurgery and intralesional steroids plus lidocaine. J Dermatol Surg Oncol. 1983;9(11):922-924.