The itching hand important differential diagnoses and treatment

Transcription

1 Review Article Submitted: Accepted: Conflict of interest None. DOI: /j x The itching hand important differential diagnoses and treatment Elke Weisshaar, Ursula Kallen, Melanie Weiß Department of Clinical Social Medicine, Occupational and Environmental Dermatology, University Hospital Heidelberg, Germany Summary Skin diseases affecting the hands receive particular individual attention and constitute a considerable emotional burden. Many dermatoses also present with itching of the hands. Itch is often underestimated when it occurs in a comparably limited body area such as the hands. The high occupational significance of the hands in many professions must, nevertheless, be stressed. One of the most frequent diagnoses in itching of the hands is eczema. In the differential diagnosis, less common diseases such as neurological and systemic diseases and adverse drug reactions must also be taken into consideration. Itching of the hands can also be accompanied by other sensations, such as burning, stinging and pain. A thorough history regarding sensations and dysesthesias already allows for a diagnostic classification of the disease in some cases. Itching of the hands requires a careful and thorough diagnostic approach. This forms the basis of a specific and successful therapy which may be adapted stepwise, depending on the underlying cause, and also may require, in addition to causal therapy, symptomatic antipruritic therapy. Therapy should follow the current guidelines for chronic pruritus and hand eczema. This article reviews over the differential diagnosis and therapy of itching hands. Background Itching of the hands can occur in a multitude of dermatological diseases. The most important differential diagnoses include eczema, particularly atopic dermatitis (AD), psoriasis palmaris and other skin diseases such as lichen planus, porphyria cutanea tarda and infectious skin diseases such as tinea manus (Table 1) [1, 2]. Systemic diseases, neurological disorders, and adverse drug reactions and even psychiatric disorders must also be considered. Rarely, congenital diseases such as progressive familial intrahepatic cholestasis, a disease with autosomal recessive inheritance, can explain pruritus of the hands already in early childhood [3]. Segmental or unilateral pruritus affecting only one hand has been reported in neurofibromatosis [4]. All of these diseases can present in the daily dermatological routine under the complaint of itching hands [1 4]. Chronic pruritus is defined as pruritus persisting over 6 weeks [2]. It is the most common symptom of dermatological diseases such as eczema, urticaria and scabies with its origin directly in the skin. Pruritus can also occur in various systemic diseases such as uremia, cholestasis, neuropathic and psychiatric disorders and can thus be triggered by hematogenous and neuronal mediators in the central nervous system [1 4]. According to the current IFSI (International Forum for the Study of Itch) classification of pruritus, 6 categories with respect to etiology (dermatologic, systemic, neurologic, somatoform/psychosomatic, mixed and unclear) are differentiated [2]. Pruritus may be associated with specific dermatological lesions, with lesion-free, clinically normal skin or with secondary scratch artifacts [2]. Pruritus of the hands can fall into all of these categories and clinical variants and thus be the result of a multitude of etiologic factors. It has been shown that the impact on quality of life due to chronic pruritus is comparable to the impact of the chronic 31

2 Table 1 Important differential diagnoses in pruritus of the hands. Eczemas Irritant (subtoxic-cumulative) Atopic Dyshidrosiform (particularly in atopic hand dermatitis, but also in other dermatitis forms) Dyshidrosis lamellosa sicca Allergic Mixed forms of irritant, atopic, allergic Dyshidrotic hand dermatitis or hyperkeratoticrhagadiform hand dermatitis, constitutional Nummular dermatitis Protein contact dermatitis Psoriasis Palmar/ palmoplantar Vulgaris (beware: inspection of further sites of predilection!) Pustulosis palmoplantaris (beware: inspection of the feet!) Infectious diseases Fungal infection: tinea manus Bacterial infections Epizoonoses: insect bites, scabies, pediculosis, cimicosis Lichen planus Lymphomas Mycosis fungoides Other cutaneous lymphomas Prurigo nodularis Neuropathic cause, for example disorders of the cervical spinal column Rarer differential diagnoses: Neuropathic pruritus of the hands Adverse drug reaction Hand-foot syndrome Erythema multiforme Granuloma annulare Verrucae vulgares Syphilis stage II (rarely pruritus) Keratoma palmare et plantare Artifacts Precancerous lesions, malignant lesions: Bowen disease, Bazex syndrome, radiodermatitis (rarely pruritus) pain syndrome [5]. Pruritus and pain are complex sensations with both common and differing signaling pathways and characteristics [6]. The well-known observation that scratching-induced pain improves or temporarily abolishes pruritus demonstrates this. Pruritus is a separate and independent sensation with its own peripheral and central processing. Nonetheless, pruritus cannot be separated from pain from the neurophysiologic perspective, because common processing and signaling pathways exist. Recent studies, for example, demonstrate that mechanosensitive pain neurons can transmit pruritus. In central imaging corresponding brain regions can be activated by pain and pruritus, and pruritus-specific brain regions do not appear to exist [6]. Possible differences exist with respect to the activation of central motor areas. The simultaneous motor activation in pruritus might correlate with planning the scratch response, while in pain, the stimulated hand is retracted [6]. In a very recent publication it could be shown that heat and pain sensations are stronger in proximal body sites than in distal body sites, while the sensation of itch behaves inversely and is thus more intense in distal body sites such as the hands [7]. Mixed sensations can occur in diseases of the hands; pruritus and pain can occur simultaneously or pruritus can be perceived with burning, tingling and painful components. Clinical examples are hand eczema with fissures, pustular psoriasis (frequently pain or mixed sensations of pruritus and pain) or neuropathies in brachioradial pruritus (BRP). In these cases it is not sufficient to speak of pruritus of the hands. Terminology that correctly describes these sensations has not yet been developed. In such cases, both patients as well as physicians speak of burning pain, itching pain or pruralgia. Differential diagnoses and clinical features Locations, morphology and symptoms (pure itch, mixed sensations of burning and itch, dominance of burning and sharp pain) can be of help in the differential diagnostic considerations in pruritus of the hand. Unilateral hand involvement may suggest tinea manus. The existence of erosions and fissures clinically may explain pain or mixed sensations. The latter can also indicate the neuropathic cause of BRP. It must be remembered that other locations besides the hands must be included in diagnostics. Therefore, the entire skin surface including scalp and the oral mucosa must always be examined. Simultaneous involvement of the feet must be searched for, which is frequently the case in dyshidrosiform hand and foot dermatitis. Lesions on the entire body may reflect hematogenous allergic contact dermatitis or another specific skin disease such as lichen planus or psoriasis. Eczema Hand eczema is the most frequent cause of pruritus of the hands. Morphology, location and etiology are employed in the classification of hand eczema [8 10]. Morphologically erythema, vesicles, infiltration and scaling typify the initial 32

3 Figure 2 A 29-year-old ceramic craftsman suffering from atopic hand dermatitis with occupational aggravation. Figure 1 Dyshidrotic hand dermatitis with closely placed, severely itching vesicles, especially on the palms of the hands, and typical dot-like or annular scaling (dyshidrosis lamellosa sicca). stage, while hyperkeratosis, fissures and lichenification of the skin predominate in chronic disease. Further, a purely vesicular (dyshidrosiform) (Figure 1), a hyperkeratotic-rhagadiform or nummular morphology may be present. Hand dermatitis can be located on the dorsa of the hands, the palms, the sides or the fingers, the fingertips, the interdigital folds and the wrist [8 10]. In irritative (subtoxic-cumulative) hand dermatitis, pruritus can particularly affect the interdigital spaces and the dorsa of the hand and fingers. The palms are involved usually only after years of disease. The phenomenon of spreading does not occur unless skin-irritating substances also contact other body sites, such as the forearms. Allergic contact dermatitis affects the contact sites such as the palms. Specific locations such as the fingertips in acrylate allergy are quite typical. Atopic skin diathesis is an important co-factor in contact dermatitis of the hands [11]. Atopic hand dermatitis typically manifests morphologically in the form of pruritic vesicles on the palms and sides of fingers as well as with involvement of the volar aspect of the wrist with eczematous lesions and typically with lichenification on the dorsa of the hands (Figure 2). The fingertips may be affected with pulpitis-sicca-like lesions. Affected patients always report of intense pruritus of the hands, while as a result of fissures usually more of a problem in the winter than in the summer a mixture of pruritus and pain or predominantly pain are reported. Nummular dermatitis may appear on the dorsa of the hands. These lesions often occur in atopic individuals or within the context of atopic dermatitis. Nummular dermatitis can also appear without atopy. Ruling out allergic contact dermatitis is mandatory. In our experience, chronic dental and otorhinolaryngeal infections, as well as Helicobacter pylori gastritis/infections, also should be excluded. In nummular dermatitis, the entire skin surface should carefully be examined to rule out other lesions of nummular dermatitis. Allergic contact dermatitis of the hands manifests after contact with the relevant contact allergens in the form of sometimes intense pruritus, erythema, vesicles followed by hyperkeratoses. Painful fissures are reported usually only in chronic courses. In occupational dermatology, allergic contact dermatitis is often observed as a secondary phenomenon superimposed on other forms of eczema. An irritant contact dermatitis usually is present over many years; the disturbed barrier function facilitates the entry of potential contact allergens. Depending on the contact allergen, the sensitization process can last months to years. An additional allergic contact dermatitis is then superimposed. In the clinical routine, mixed forms of irritant and allergic contact dermatitis predominate in these cases. In allergic contact dermatitis the lesions occur on skin sites with contact to the allergen (Figure 3). 33

4 Figure 4 Chronic pruritus (n = 913) according to location in 2,380 participants of a skin protection workshop for secondary individual prevention initiated by the German Social Accident Insurance Institution for the Health and Welfare Services (BGW), Karlsruhe, for health care, cleaning and kitchen workers. Figure 3 A 60-year-old construction worker with multiple occupationally relevant type IV sensitizations causing severe allergic contact dermatitis. When the contact allergen is volatile, the corresponding lesions with pruritus can also develop at sites not covered by clothing such as the face/head, neck, arms and chest. By appropriate careful allergological testing it is usually possible to identify the responsible contact allergen. Usually a temporal relationship exists between exposure to the allergen and the onset of pruritus or the onset of the skin disease. Hand dermatitis preferentially develops in various occupational groups with skin irritation [12, 13]. Of 1,742 employees in health care professions who participated in a skin protection seminar of secondary individual prevention (SIP) of the German Social Accident Insurance Institution for the Health and Welfare Services (BGW) in Karlsruhe [12, 13], 25.7 % (n = 448) had irritant hand dermatitis, 4.3 % (n = 74) allergic contact dermatitis and 12.7 % (n = 222) atopic hand dermatitis (status December 2011). Of those employed in the health care sector, 45.5 % (n = 792) suffered from a mixed form of the above-mentioned diagnoses, with the simultaneous occurrence of irritant and atopic hand dermatitis being the most common of the mixed forms (27.9 %, n = 486). Of the 638 SIP participants employed as cleaning workers in contrast 32.2 % (n = 206) had irritant hand dermatitis, while in 2.8 % (n = 18) allergic contact dermatitis and in 6.1 % (n = 39) atopic hand dermatitis was diagnosed. A mixed form of all mentioned diagnoses was found in 45.8 % (n = 293) with the mixed form of irritant and atopic hand dermatitis being the most common with 26.9 % (n = 172). An atopic skin diathesis [11] was present in 63.9 % of all participants, with 66.8 % of those employed in the health care field and 56.3 % engaged in cleaning work being atopic individuals. Of the 913 participants in the SIP workshops complaining of pruritus (38.4 %), 63.8 % reported pruritus on the hands, 13.1 % pruritus on the body and 23.1 % in both locations (Figure 4). Of the participants with irritant hand dermatitis, interestingly 78.0 % complained of pruritus of the hands, making this diagnosis the most frequent among participants with pruritus of the hands (Figure 5). Of participants with atopic hand dermatitis, 24.5 % reported pruritus of the hands, while 39.4 % of this group complained of pruritus on the hands and body; thus, patients with atopic dermatitis most frequently had pruritus on the entire body (Figure 5). More current results on pruritus of the hands are provided by the carpe CHE Registry (registry of chronic hand eczema and long-time patient management), which in September 2011 contained 1036 patients [14]. 40.7% (n = 422) of the patients showed atopic skin diathesis (unpublished data). In total, 80.9% (n = 838) of the CHE registry patients declared to suffer from pruritus, mild pruritus being most frequent with 33.7% (figure 6). Furthermore, the intensity of pruritus appeared to correlate with the severity level of hand eczema and the impairment of skin-related quality of life (measured with DLQI, the dermatological index for quality of life) [14]. 34

5 Figure 5 Frequency and location of chronic pruritus in 2,380 participants of skin protection workshops for secondary individual prevention, initiated by the German Social Accident Insurance Institution for the Health and Welfare Services (BGW), Karlsruhe, depending on diagnosis. Palmar psoriasis Psoriasis can lead to localized or generalized pruritus, which is a common but often ignored and underestimated symptom in patients with psoriasis [15]. This may, on the one hand, be due to a lower frequency and intensity of pruritus in comparison to other pruritogenic disease such as atopic hand dermatitis, as well as impairment of psychosocial health which may particularly manifest as social withdrawal [15]. Most studies report that pruritus in plaque psoriasis that does not present on the hands. A recent comprehensive review of studies on the subject of pruritus and psoriasis demonstrated that in most studies, the hands were not taken into consideration as a location affected by pruritus, but possibly only assigned to the location arms or limbs. The location arm was reported with a frequency of about 70 % in most studies [15]. In the daily occupational dermatology practice, palmar psoriasis represents an important clinical differential diagnosis. According to the experience gained from SIP workshops and occupational dermatology inpatient treatment (tertiary individual prevention, TIP) [12, 13, 16], 5 10 % of the dermatoses of the hands represent palmar psoriasis. Clinically, most often one sees infiltrated plaques located symmetrically over the metacarpophalangeal and interphalangeal joints (Figure 7). The palms are particularly affected presenting with relatively homogenous involvement with fissures. Pustular palmoplantar psoriasis is rarely if ever associated with pruritus (Figure 8). Those affected usually report pain [17]. Clinically, the differentiation between eczema and psoriasis can be difficult, with mixed forms (secondary eczematization of existing palmar psoriasis) also having to be considered [15] (Figure 7). Clinically helpful in such cases are exact Figure 6 Pruritus intensity at the first visit in patients (n = 1,036) of the carpe study (chronic hand eczema registry on long-term management of patients) [14]. allergological diagnosis, comprehensive history and possibly even a biopsy, keeping in mind that the diagnosis of psoriasis, particularly in biopsies of palmar skin, is often difficult. Lichen planus Lichen planus is a skin disease characterized by pruritic polygonal papules (Figure 9) that in its classic form does not preferentially manifest on the hands. Sites of predilection of eruptive exanthematous lichen planus are the wrists and forearms that must also be considered in pruritus of the hands. Palmar and plantar skin is rarely affected usually. The diagnosis can usually be made on the basis of clinical inspection, the oral mucosa with the Wickham phenomenon and nail lesions (onychoschizia, irregular pits and ridges, thinning of the nail plate) providing clues. According to a recent study 96.7 % of patients with lichen planus suffered from pruritus, with this being more intense than in patients with psoriasis [18]. This study also demonstrates that pruritus in lichen planus frequently ceases after initiation of appropriate therapy, while it ceases in psoriasis only with complete healing of all cutaneous lesions [18]. Patients with lichen planus more frequently report pruritus of the upper limbs; a differentiated description for example of the hands is not included in this study [18]. Lymphoma Particularly in recalcitrant, especially hyperkeratotic-rhagadiform hand dermatitis that does not heal despite intensive therapy, a lymphoma must be considered in differential diagnosis. These are usually characterized by moderate to severe pruritus; in the tumor stage (mycotic stage) pruritus can be very severe and is usually difficult to control. The clinical 35

6 Figure 8 Pustular psoriasis in a 59-year-old nurse with densely placed vesicles on erythematous skin on the palms of the hands and the soles of the feet, particularly intense on the palms as well as on the flexural and periungual regions of both great toes. Figure 7 Mixed form of palmar psoriasis and irritant contact dermatitis in a 55-year-old geriatric nurse. Since childhood, the patient had suffered from psoriasis vulgaris. In the last 15 years, she has had erythematous scaly plaques over the metacarpophalangeal and interphalangeal joints, as well as vesicles, erythema and hyperkeratoses on the sides of thumbs and fingers. presentation of lymphomas is highly variable and depends on stage. Eczema-like, psoriasiform and leaf-like lesions can exist, with arthropod-assault-like cutaneous reactions also having been described in mantle cell lymphoma [19]. Particularly in the case of unspecific clinical and histological findings, for example in the premycotic stage, the diagnosis of a lymphoma can be overlooked. Additional diagnostic considerations Depending on clinical features, infectious diseases such as tinea manus, bacterial infections and scabies must be excluded by appropriate diagnostic measures. Tinea manus (Figure 10) typically presents with round erythematous lesions with Figure 9 Clinical variants of lichen planus of the hand with moderate but persistent pruritus. accentuated borders that can be accompanied by pruritus. Dry, powdery palmar scaling without signs of significant inflammation is also typical. Often only one hand is affected. Intense scratching can alter the clinical picture, so that it no longer resembles a typical fungal infection. In scabies, typically small papules are found in the interdigital spaces; in childhood the clinical picture may also include dyshidrosiform, pustular lesions. Palms are typically spared because of their thick, mechanically stable stratum corneum, but can be affected in small children, the elderly and members of the nursing profession due to manual transfer (Figure 11). Diagnostic clues are comma-like, linear, winding mite burrows measuring a few millimeters that can be followed papules and papulovesicles due to scratching. Porphyria cutanea tarda must be considered, when blisters repeatedly appear on the dorsa of the hands that are more strongly associated with pain than pruritus on the background of fragile and sensitive skin, sometimes with poorly healing wounds. Here, appropriate diagnostic studies (Table 2) should be performed. Hemorrhagic 36

7 Figure 10 Tinea manus with erythema of the palms and scaling. Diagnostic clue: unilateral involvement. Figure 11 Scabies of the hands with red, itching papules and papulovesicles on the palm of the left hand in a 42-year-old male nurse working in a nursing home. blisters, erosions, crusts and milia, as well as hyper- and hypopigmented scars can also be found in all sun-exposed areas of the skin. As the lesions preferentially develop at sites with great mechanical stress (by repeated microtrauma), the dorsa of the hands and forearms are most often affected. Attention should be paid to the fact that the triggers of porphyria cutanea tarda can be highly variable; among others, medications such as ciprofloxacin have been reported as triggers [20]. Prurigo nodularis Prurigo nodularis means the development of skin nodules that are secondary reactive alterations as a result of chronic scratching due to chronic pruritus. According to the international classification they correspond to group 3, i.e. secondary lesions acquired through scratching [2]. Prurigo nodularis frequently develops within the context of a chronic skin disease, especially AD or atopic skin diathesis [21], but also in a systemic disorder such as terminal renal insufficiency. Therefore, the identification of the underlying cause is most important in therapy [22]. In BRP (see below) one should look for prurigo nodularis on the dorsa of the hands and extensor surfaces of forearms and upper arms (Figure 12). Clinical features and location do not automatically indicate the underlying cause. Brachioradial pruritus Brachioradial pruritus (BRP) is a form of pruritus of primarily extracutaneous origin affecting the nape, the upper back and the extensor surfaces of the upper arms and forearms usually appearing symmetrically and also often involving the dorsa of the hands [23 26] (Figure 13). When nerve compression affects the dorsal skin branch of the ulnar nerve, this is termed cheiralgia paraesthetica, which can present with pruritus of the hands. BRP may extend beyond the region of the M. brachioradialis until the chest. Pure itch rarely predominates clinically, more likely mixed sensations of itch, burning and pain [23 26] in the dermatome C5 and C6 [24, 25]. Seasonal variation of symptoms, particularly in the summer months, might suggest UV light as a possible trigger factor [24]. In a recent study, all patients had alterations of the spinal column identifiable in magnet resonance imaging (MRI). In 80.5 % of those affected, stenosis of the intervertebral foramina or protrusion of the cervical intervertebral discs with the corresponding nerve compression was observed [25]. Spinal tumors must also be considered as cause [22, 23, 26]. Therefore, an appropriate neurological and especially radiological evaluation including MRI particularly of the cervical and thoracic spinal column is indicated. Hand-foot syndrome Hand-foot syndrome is also known as palmoplantar erythrodysesthesia or chemotherapy-associated acral erythema. Clinically, painful erythema is observed on palms and soles with dysesthesias such as a prickling sensation and tickling, while pain predominates. It is unclear if this represents a single disease entity or a heterogeneous collection of various disorders with differing underlying mechanisms [27]. In recent times, the disorder has been reported as a side effect particularly of the multikinase inhibitors (MKI) sorafenib and sunitinib [27, 28]. Other possible drug triggers also include doxorubicin, taxanes, 5-fluorouracil and capecitabine (prodrug of 5-fluorouracil) [29, 30]. 37

8 Table 2 Diagnostic procedures in pruritus of the hands. History (mandatory) Duration, course, symptoms, temporal relationships (e.g. with the use of topical and systemic medications), occupational and leisure activity history, disease course during work vs. weekend and vacation Preexisting conditions in general, skin diseases, atopy, allergies Medications, smoking and alcohol consumption Lifestyle (skin care, hobbies, household activities) Clinical examination (mandatory) Inspection of the entire body and mucous membranes General physical examination including lymph node status Laboratory studies (according to history, especially in the event of a systemic cause) ESR, CRP, blood count with differential blood count, urea, creatinine, GGT, TOT, GPT, glucose When indicated, HbA1c, antibody serology, antistreptolysin/ antistaphylolysin titer, TSH, iron, ferritin. Further studies according to history, e.g. ANA, H. pylori serology, hepatitis serology (also see [22]) Depending on diagnosis (for example in lymphomas: immunophenotyping, molecular biological studies) Urin analysis Mycology, bacteriology (according to clinical findings) Smears, cultures Histology (according to clinical findings) Skin biopsy with dermatohistopathologic evaluation including special stains, immunohistology and/or electron microscopy as indicated Allergology (when contact dermatitis or contact urticaria is suspected) Laboratory: total IgE and specific IgE (IgE-RAST), tryptase, mast cell metabolites Allergy test (with evaluation of the clinical relevance): Patch test Mandatory: Standard series or standard series for children Depending on history: Hairdressing supplies, disinfectants, ingredients of topical products, topical antibiotics, antifungal agents, further medications, preservatives, fragrances and essential oils, rubber chemicals, plants, dental metals, corticosteroids, synthetic resins/ glues In photoallergic contact dermatitis: Minimal erythema dose, photo patch test Sodium lauryl sulfate as an indictor of skin irritability (also following the guideline for chronic pruritus) Prick testing: atopic allergens, moulds, medications, latex food stuffs Supplemental consultations (depending on findings) Internal medicine Neurology Orthopedics Psychosomatic medicine, psychiatry Further studies (depending on findings and especially in the case of brachioradial pruritus and prurigo nodularis of the hands, arms and/or upper trunk) Radiologic diagnostics (MRI when neuropathic pruritus is suspected) Somatoform pruritus Mental factors can also significantly impact the course of skin diseases, including dermatoses of the hands [31 33]. About 50 % of patients with dermatoses of the hand are convinced that stress affects the course of their skin disease [31]. In this study, it was also demonstrated that the subjective reaction to stress correlates with the severity of the skin disease, depression and the experience of significant life events [31]. In hand dermatoses or pruritus of the hands, compulsive disorders such as compulsive hand-washing must be considered as well [32]. These patients are controlled by compulsive thoughts. The repetitive and continuous impulses can 38

9 Figure 12 Prurigo nodularis in a patient with underlying psychiatric disease. The upper body and the upper limbs revealed multiple partly excoriated nodules. The legs showed multiple skin lesions appearing as if pierced, which were classified as artifacts due to self-mutilation. The 67-year-old patient reported intense chronic pruritus of the entire skin; self-mutilation of the legs was denied. result in the manifestation of irritant hand dermatitis. In addition to adequate dermatologic therapy, psychotherapy (behavioral therapy) and often drug therapy is necessary here. Artifacts (intentional generation or pretending of physical or mental symptoms) must also be considered [33]. Artifacts may be found on the hands, confounding the expert assessment of occupational diseases and disability determinations [33]. Erythema, swelling, infiltration, erosions, crusts and necrotic areas can be seen. Clinical examination in some cases allows for interpreting the cause of the lesion that can be produced in various manners such as rubbing, biting, scratching, cutting and suctioning the skin. This disorder demands psychosomatic care and therapy, while those affected in the case of intentional or conscious simulation are hardly accessible to psychotherapeutic measures, as no motivation exists. While diseases of relevance to occupational dermatology usually affect the hands, in the case of artifacts lesions on the entire body must be evaluated, as the lower legs are also easily accessed (Figure 12). Diagnostic approach Figure 13 Chronic pruritus with excoriated nodules and plaques in the sense of neuropathic pruritus in a 55-year-old patient with chronic pruritus of the hands, the arms and the genital region and a history of multiple herniated vertebral discs in the lumbo-sacral region and degenerative processes in the cervical spine region. Pruritus of the hand demands a painstaking work-up (Table 2). This always includes a comprehensive history and dermatologic examination. This encompasses exact registration of the sensations, the involved locations as well as dermatologicallergologic and general medical history. In pruritus of the hand, the complete occupational history plays a particularly important role, as hand dermatitis as cause of pruritus of the hands is particularly frequent in manual labor and other occupations with skin irritation [12, 13, 16]. A history of leisure activities is also of significance with respect to manual hobbies such as constructing models, working on motor vehicles or even knitting, very popular again among women of all age groups. As therapy needs to be oriented on the cause of pruritus, careful diagnosis is of utmost importance [9, 22]. The extent of the evaluation depends on the symptoms, clinical features and the severity of pruritus as well as the findings obtained during evaluation (Table 2). Particularly in cases when the cause of pruritus cannot be classified by clinical examination and morphological assessment, a comprehensive work-up according to the current guideline on chronic pruritus [22] should be performed. In accordance with our own extensive experience in the field of chronic pruritus, occupational dermatology and in the diagnostics and therapy of hand dermatoses, a diagnostic approach to pruritus of the hands as presented in Table 2 is recommended. Therapy Comprehensive and thorough diagnosis is an important foundation for therapy. The extent of the diagnostic evaluation and the resulting therapy is oriented on the symptoms, clinical findings and the severity of pruritus. If it is obvious that the pruritus is exclusively caused by hand dermatitis will we follow the stepwise therapy of hand dermatitis according to the degree of severity [9]. The therapy of pruritus of the hands depends on the underlying cause, clinical features, the history (allergic contact dermatitis, occupation) as well as the individual therapeutic response (Table 3). For this we refer to the guidelines on chronic pruritus, on chronic hand dermatitis and on therapy of psoriasis [9, 22, 34 36]. A case collection from occupational dermatology with highly pruritogenic hand dermatitis demonstrated good efficacy of systemic therapy with alitretinoin in hyperkeratotic-rhagadiform and dyshidrosiform hand dermatitis and in pustular psoriasis [37]. 39

10 Table 3 Therapeutic algorithm for pruritus of the hands. General approach depending on skin condition and diagnosis: Hand baths (disinfectant, tanning agents) Emollients (ideally without fragrances or preservatives), stage-adapted topical therapy (also see below) Particularly in occupations with skin irritation: Instruction on skin care measures, skin protection (when indicated glove counseling) and, when appropriate, maintaining factors and trigger substances Avoidance of exposure (contact allergens, wet work, skin-irritating substances) Symptomatic-antipruritic topical therapy (e.g. polidocanol, tanning agents, combinations of ointments and wet dressings, menthol) Systemic antihistamines such as cetirizine, desloratadine (effective in case of an allergic cause, high-dose therapy when needed: desloratadine 3 x 10 mg, also effective for other indications) In case of occupational relevance: submitting a dermatologist s report, perhaps inspection of the working place Perhaps skin protection workshop, atopic dermatitis and/or pruritus educational program [12, 13, 38, 39] In hand dermatitis: (also see [9]) In step 1: antiseptics and symptomatic-antipruritic agents, topical corticosteroids, topical calcineurin inhibitors, tap water iontophoresis (in case of dyshidrosis, hyperhidrosis) In step 2: in addition to step 1 highly potent topical corticosteroids, UV phototherapy, alitretinoin In step 3: in addition to step 1 and 2 alitretinoin, systemic corticosteroids (only on a short-term basis) cyclosporine When bacterial infections are suspected: Topical and/or systemic antibiotics according to smear with microbiological culture and sensitivity, broad-spectrum antibiotics only on a short-term basis (beware: contact sensitization, secondary fungal infections) When a fungal infection is suspected: First identification of the pathogen and unspecific disinfection Topical antifungal agents, when needed also systemic antifungal agents according to culture and sensitivity When allergic contact dermatitis, contact urticaria or protein contact dermatitis is suspected: Allergological diagnostics including patch and prick testing, perhaps scratch testing, specific IgE Examples of further therapies according to the diagnosis made: UV phototherapy: cream PUVA therapy, bath PUVA therapy Topical corticosteroids, topical calcineurin inhibitors Discontinuation of causative or triggering medications, for example beta blockers, multikinase inhibitors Topical and systemic antipsoriatic agents Acitretin in psoriasis, lichen planus Cyclosporine in psoriasis, atopic dermatitis, prurigo nodularis Gabapentin, pregabalin, naltrexone in neuropathic pruritus, prurigo nodularis Serotonin reuptake inhibitors, tetracyclic antidepressants in somatoform pruritus, prurigo nodularis Stage-adapted lymphoma therapy Conclusions Due to the exposed nature of hands, a skin disease affecting them receives special individual attention and may have a significant mental impact. Many skin diseases on the hands are also associated with chronic pruritus. A tendency exists to underestimate this when it occurs on a comparably small area of the body. At the same time, the great significance of the hands as working tools in many professions must be stressed. The most important differential diagnosis of pruritus of the hands is the group of eczemas. Other diseases such as BRP can be associated with sensations such as burning, piercing and pain in the skin, which in some cases facilitates the differential diagnostic classification of the disease. Pruritus of the hands demands a thorough diagnostic approach. This is the foundation of targeted therapy that depending on the underlying cause can be adapted in a stepwise fashion and includes besides causal therapy symptomatic antipruritic therapy. Therapy should be planned in accordance with the current guidelines on therapy of chronic pruritus, of hand dermatitis and further specific guidelines, for example on therapy of psoriasis vulgaris [9, 22, 36]. 40

11 Correspondence to Prof. Dr. Elke Weisshaar University Hospital Heidelberg Department of Clinical Social Medicine Occupational and Environmental Dermatology Thibautstraße Heidelberg, Germany elke.weisshaar@med.uni-heidelberg.de References 1 Weisshaar E, Dalgard F. Epidemiology of itch: Adding to the burden of skin morbidity. Acta Derm Venereol 2009; 89: Ständer S, Weisshaar E, Mettang T, Szepietowski JC, Carstens E, Ikoma A, Bergasa NV, Gieler U, Misery L, Wallengren J, Darsow U, Streit M, Metze D, Luger TA, Greaves MW, Schmelz M, Yosipovitch G, Bernhard JD. Clinical classification of itch: a position paper of the International Forum for the Study of Itch. Acta Derm Venereol 2007; 87: Ooi BC, Phua KB, Lee BL, Tan CE, Ng ISL, Quak SH. Lichenification and enlargement of hands and feet: a sign of progressive familial intrahepatic cholestasis with normal gammaglutamyl-transpeptidase. J Pediatr Gastroenterol Nutr 2001; 32: McFadden JP, Logan R, Griffiths WAD. Segmental neurofibromatosis and pruritus. Clin Exper Dermatol 1998; 13: Kini SP, DeLong LK, Veledar E, McKenzie-Brown AM, Schaufele M, Chen SC. The impact of pruritus on quality of life: the skin equivalent of pain. Arch Dermatol 2011; 147: Ständer S, Raap U, Weisshaar E, Schmelz M, Mettang T, Handwerker H, Luger TA. Pathogenese des Pruritus. J Dtsch Dermatol Ges 2011; 9: Truini A, Leone C, Di Stefano G, Biasiotta A, La Cesa S, Teofoli P, Padua L, Cruccu G. Topographical distribution of warmth, burning and itch sensations in healthy humans. Neurosci Lett 2011; 494: Diepgen TL, Andersen KE, Brandao FM, Bruze M, Bruynzeel DP, Frosch P, Goncalo M, Goossens A, Le Coz CJ, Rustemeyer T, White IR, Agner T. Hand eczema classification: a crosssectional, multicentre study of the aetiology and morphology of hand eczema. Br J Dermatol 2009; 160: Diepgen TL, Elsner P, Schliemann S, Fartasch M, Kollner A, Skudlik C, John SM, Worm M. Management von Handekzemen. Leitlinie. ICD-10 Code: L20. L23. L24. L25. L30. J Dtsch Dermatol Ges 2009; 7: Molin S, Diepgen TL, Ruzicka T, Prinz JC. Diagnosing chronic hand eczema by an algorithm: a tool for classification in clinical practice. Clin Exp Dermatol 2011; 36: Diepgen TL, Fartasch M, Hornstein OP. Kriterien zur Beurteilung der atopischen Hautdiathese. Dermatosen 1991; 39: Soder S, Diepgen TL, Radulescu M, Apfelbacher CJ, Bruckner T, Weisshaar E. Berufsbedingte Hauterkrankungen bei Beschäftigen in Reinigungs- und Küchenberufen: Verlauf und Lebensqualität nach Maßnahmen der sekundären Individualprävention. J Dtsch Dermatol Ges 2007; 5: Weisshaar E, Radulescu M, Bock M, Albrecht U, Zimmermann E, Diepgen TL. Hautschutzseminare zur sekundären Individualprävention bei Beschäftigten in Gesundheitsberufen: Erste Ergebnisse nach über 2-jähriger Durchführung. J Dtsch Dermatol Ges 2005; 3: Apfelbacher CJ, Molin S, Weisshaar E, Bauer A, Schmitt J, Mahler V, Ruzicka T, Elsner P. Itching in chronic eczema: Results from the carpe registry. Acta Derm Venereol 2011; 91: Weisshaar E. Pruritus und Psoriasis. Eine wichtige, aber häufig unterschätzte Verbindung. Hautarzt 2012; 63(7): Skudlik T, Weisshaar E, Scheidt R, Elsner P, Wulfhorst B, Schönfeld M, John SM, Diepgen TL. First results from the multicentre study rehabilitation of occupational skin diseases optimization and quality assurance of inpatient management (ROQ). Contact Dermatitis 2012; 66: Weisshaar E, Diepgen TL. Erfolgreiche Etanercepttherapie bei therapierefraktärer Acrodermatitis continua suppurativa Hallopeau. J Dtsch Dermatol Ges 2007; 5: Reich A, Welz-Kubiak K, Szepietowski JC. Pruritus differences between psoriasis and lichen planus. Acta Derm Venereol 2011; 91: Dodiuk-Gad RP, Dann EJ, Bergman R. Insect bite-like reaction associated with mantle cell lymphoma: a report of two cases and review of the literature. Int J Dermatol 2004; 43: Degiovanni CV, Darley CR. Pseudoporphyria occurring during a course of ciprofloxacin. Clin Exp Dermatol 2008; 33: Iking A, Grundmann S, Chatzigeorgakidis E, Phan NQ, Klein D, Ständer S. Prurigo as a symptom of atopic and non-atopic diseases: aetiological survey in a consecutive cohort of 108 patients. J Eur Acad Dermatol Venereol Feb 25. doi: /j x. [Epub ahead of print]. 22 Ständer S, Darsow U, Mettang T, Gieler U, Maurer M, Ständer H, Beuers U, Niemeier V, Gollnick H, Vogelgsang M, Weisshaar E. S2-Leitlinie Dermatologie: Chronischer Pruritus, Reg.-Nr. 013/ html (Stand: ). 23 Schürmeyer H, Fischbach R., Nabavi D, Metze D, Ständer S. Brachioradialer Pruritus. Eine seltene, lokalisiere, neuropathische Juckreizform. Hautarzt 2006; 57: Veien NK, Laurberg G. Brachioradial pruritus: a follow-up of 76 patients. Acta Derm Venereol 2011; 91: Marziniak M, Phan NQ, Raap U, Siepmann D, Schürmeyer- Horst, Pogatzki-Zahn E, Niederstadt T, Ständer S. Brachioradial pruritus as a result of cervical spine pathology. The results of a magnetic resonance tomography study. J Am Acad Dermatol 2011; 65: Oaklander AL: Common neuropathic itch syndromes. Acta Derm Venereol 2012; 92: Degen A, Alter M, Schenck F, Satzger I, Völker B, Kapp A, Gutzmer R. Das Hand-Fuß-Syndrom als Nebenwirkung der medikamentösen Tumortherapie Klassifikation und Management. J Dtsch Dermatol Ges 2010; 8:

12 28 Kim DH, Son IP, Lee JW, Lee HI, Kim BJ, Kim MN. Sorafenib (Nexavan BAY )-induced Hand-foot Skin Reaction with Facial Erythema. Ann Dermatol 2011; 23: Disel U, Gurkut O, Abali H, Kaleagasi H, Mertsoylu H, Ozyilkan O, Saif MW. Unilateral hand-foot syndrome: an extraordinary side effect of capecitabine. Cutan Ocul Toxicol 2010; 29: Latif S, Fraga G, Gadzia J. Increased mast cell density in capecitabine-induced hand-foot syndrome: a new pathologic finding. J Drugs Dermatol 2010; 9: Niemeyer V, Nippesen M, Kupfer J, Schill WB. Psychodermatology Psychological factors associated with hand dermatosis: Which subgroup needs additional psychological care? Br J Dermatol 2002; 146: Shab A, Matterne U, Diepgen TL, Weisshaar E. Werden Zwangs- und Persönlichkeitsstörungen bei Berufsdermatosen ausreichend berücksichtigt? Eine Diskussion anhand von 3 Fallbeispielen. J Dtsch Dermatol Ges 2008; 6: Shab A, Becker M, Diepgen TL, Weisshaar E. Berufsdermatose oder artifizielle Dermatose? Dermatologie in Beruf und Umwelt 2008; 56: Bissonnette R, Diepgen TL, Elsner P, English J, Graham-Brown R, Homey B, Luger T, Lynde C, Maares J, Maibach HI. Redefining treatment options in chronic hand eczema (CHE). J Eur Acad Dermatol Venereol 2010; 24: Kragballe K. Management of difficult to treat locations of psoriasis. Scalp, face, flexures, palm/soles and nails. Curr Probl Dermatol 2009; 38: Nast A, Boehncke WH, Mrowietz U, Ockenfels HM, Philipp S, Reich K, Rosenbach T, Sammain A, Schlaeger M, Sebastian M, Sterry W, Streit V, Augustin M, Erdmann R, Klaus J, Koza J, Müller S, Orzechowski HD, Rosumeck S, Schmid-Ott G, Weberschock T, Rzany B. S3-Guidelines on the treatment of psoriasis vulgaris (English version). Update. J Dtsch Dermatol Ges 2012; 10 Suppl 2: S Weisshaar E, Fröhlich M, Diepgen TL. Alitretinoin bei chronischem Handekzem Falldarstellungen aus berufsdermatologischer Sicht. Dermatologie in Beruf und Umwelt 2012; 60: Staab D, Diepgen TL, Fartasch M, Kupfer J, Lob-Korzilius T, Ring J, Scheewe S, Scheidt R, Schmid-Ott G, Schnopp C, Szczepanski R, Werfel T, Wittenmeier M, Wahn U, Gieler U. Age-related, structured education programmes improve the mangement of atopic dermatitis in children and adolescents: results of the German Atopic Dermatitis Intervention Study (GADIS). Br Med J 2006; 332: Bathe A, Matterne U, Dewald M, Grande T, Weisshaar E. Educational multidisciplinary training programme for patients with chronic pruritus. Acta Derm Venereol 2009; 89: