Contact Dermatitis

Brachioradial pruritus is an enigmatic entity characterized by pruritus localized to the skin overlying the proximal heads of the brachioradialis muscle, with few other clinical symptoms.1-5 It was first described by Waisman⁶ in 1968. Brachioradial pruritus characteristically affects middle-aged women residing in tropical to temperate climates, though it may occur in males and individuals residing in other climates.1-8 It often presents as tingling, burning pruritus on the dorsal aspect of the forearm. Pruritus may be unilateral or bilateral and may extend up the arm and across the upper back. It often is described as burning, stinging, or painful, and is seasonal in nature, often presenting in late summer and lasting into December.1-5 Brachioradial pruritus was originally associated with solar exposure and UV radiation. Later, Heyl9 proposed that cervical nerve root impingement or injury secondary to cervical trauma was causative. Although a true cause remains elusive, both actinic damage and cervical spine disease are likely involved. We discuss an otherwise healthy woman who presented with nonspecific pruritus consistent with brachioradial pruritus.

Case Report
A 46-year-old woman presented with persistent pruritus of the left proximal lateral forearm. The pruritus had been present for several years and was recalcitrant to a multitude of therapeutic modalities, including topical corticosteroids and oral antihistamines. Application of heat did not affect her symptoms; however, application of cold compresses did alleviate some of the pruritus. Her medical history was noncontributory. Her surgical history was pertinent for prior anterior cervical discectomy and fusion from C4 to C6. Physical examination revealed no obvious cutaneous lesions in the site other than mild erythema secondary to scratching. Magnetic resonance imaging of her cervical spine revealed a left-sided osteophyte causing minimal left neural foraminal stenosis at the level of C3 to C4 (Figure). Electromyography and nerve conduction velocity studies of the left upper extremity revealed a mildly prolonged left median sensory latency. The patient was treated with topical capsaicin cream with moderate success. She also was advised to avoid sun exposure to the affected area.

Comment
Brachioradial pruritus affects a focal circumscribed area of the proximal lateral forearm. The area typically involves a sun-exposed region and may include the forearm, arm, shoulder, neck, and/or upper thorax.2 Middle-aged women are most commonly affected, with tingling, burning, and pruritus of the affected area.1 Symptoms may last from August to December and may subside during the winter.1-5 Pruritus may be unilateral or bilateral. The nature of the pruritus is often described as burning, stinging, or painful, and manifests a seasonal relation, with high incidence in late summer corresponding with the highest UV exposure.1 Patients may report intensification of pruritus with scratching, which may be related to damage of peripheral nerve fibers.2,10 This intensification may, in part, be secondary to chronic UVA irradiation.11 Involvement of C fibers containing neuropeptides responsible for pruritus explains the rationale for treatment with topical capsaicin.2,5 Application of ice often is the only means of alleviating pruritus.10,12 The consistency of relief with ice is useful in the diagnostic screening of this entity.10 The neurophysiology of pruritus is not fully understood. However, it is known that Aδ and C fibers are responsible for the transmission of pruritus.9 Pruritus can be categorized as pruritoceptive (originating in the skin) or neurogenic (originating in the central nervous system), or a combination of both. The Aδ and C fibers are co-responsive to temperature change as well as pruritus. Increases in skin temperature lower the threshold of cutaneous pruritus receptor units.13 The neural pathway for pruritus has been established. Nociceptor C fibers transmit impulses to the dorsal horn of the spinal cord and then to the thalamus via the spinothalamic tract.14 Scratching typically relieves the sensation of pruritus.15 The gate-control theory postulates that afferent sensory input from cutaneous C fibers is modulated by a gate-control system at the level of the spinal cord.5,16,17 A subsequent Aδ impulse may act in a negative feedback method to shut off C-fiber stimulation. However, stimulation of Aδ fibers in brachioradial pruritus paradoxically seems to potentiate the sensation of pruritus.5 Wallengren5 suggested that local damage to peripheral nerve fibers could be responsible for this potentiation of pruritic sensation. Kumakiri et al18 demonstrated ultrastructural damage to dermal nerve fibers following UVA irradiation. UV radiation has been shown to cause a sensitizing effect on sensory nerve fibers and lower the threshold for sensory nerve stimulation, which may occur via direct effects of UV exposure or by release of neural mediators.19 The pathophysiology of brachioradial pruritus is controversial. The 2 proposed associations are UV exposure and cervical spine disease.20 Wallengren and Sundler2 proposed that solar-induced nerve injury is responsible for brachioradial pruritus. UV radiation may be an eliciting factor, while cervical spine disease may be a predisposing factor.2 On the contrary, Fisher21 reported on the association of cervical nerve root impingement and involvement of 1 or more of the C5 to C8 cervical nerve root segments. Brachioradial pruritus has been reported in association with an ependymoma and secondary to cervical nerve compression.9,22 In a report by Heyl,9 4 of 14 patients demonstrated evidence of degenerative changes and osteoarthritis between C4 and C7. In addition, Heyl9 noted that brachioradial pruritus may be caused by compression of structures not identified by cervical radiographs. In a series of 11 patients with brachioradial pruritus who underwent radiography of the spine, Goodkin et al12 found that all patients demonstrated radiographic abnormalities of the cervical spine. Magnetic resonance imaging is the most reliable diagnostic method for cervical nerve root compression.20,22 Recently, Crevits20 suggested that neural damage from peripheral nerves by solar radiation or local injury or from central sensory pathways, such as cervical spine disease, is a nonspecific cause. In view of the literature, a definitive pathophysiology for brachioradial pruritus does not exist. It is clear that it is a unique clinical entity, but the pathophysiologic basis is not known. While the association between cervical spine disease and brachioradial pruritus is not fully understood, the prevalence of cervical spine disease is higher in patients with brachioradial pruritus.12 It has not been determined if this association is causal or causative.20 A similar localized itch syndrome, notalgia paresthetica (NP), also has been examined with respect to cervical spine pathology.12,23-25 NP is similar to brachioradial pruritus but involves the dorsal spinal nerves. Savk et al23 found the presence of vertebral column pathology in 7 of 10 patients with NP. A subsequent larger study involving 43 patients with NP reported that in 34 patients (79%), spinal pathology had been detected by radiographs. Additionally, in 65% of patients (28/43), changes were most prominent in the vertebrae and corresponded to clinically involved dermatomes.24 However, not all pathologies are detectable via radiographic imaging.25 Thus, Savk and Savk25 reinforced the necessity of clinical and radiographic examination. Histologic examination is not necessary for the clinical diagnosis of brachioradial pruritus. Cutaneous biopsies most often demonstrate nonspecific findings and/or chronic solar damage. Wallengren and Sundler2 compared cutaneous biopsies in afflicted and control patients utilizing antibodies against a pan-neuronal marker, protein gene product 9.5, calcitonin gene-related peptide, and vanilloid receptor subtype 1 (VR1) for capsaicin-sensitive nerve structures. The number of protein gene product 9.5 immunoreative nerve fibers was reduced in pruritic skin by 23% to 43%.2 These findings suggest that brachioradial pruritus may be elicited by exposure to UV radiation and/or heat. Wallengren and Sundler2 noted one patient who relapsed with pruritus during the winter following use of a heating pad to relieve neck pain, which supports the notion that UV radiation and/or heat may be causative. Immunohistochemical studies demonstrated protein gene product 9.5 immunoreactive nerve fibers in a dense population in the epidermis and the dermis and calcitonin gene-related peptide immunoreactive nerve fibers located primarily in the dermis. Capsaicin-sensitive VR1 immunoreactive nerve fibers were located as free nerve fibers.2 Wallengren and Sundler2 proposed that the VR1 structures are associated with thermoreception. The reduction in nerve fibers via all markers in patients with brachioradial pruritus implicates their role. Furthermore, these histologic changes resemble those found in patients after serial phototherapy.2,26 Underlying cervical spine disease may amplify this pruritus. Treatment of brachioradial pruritus includes a multitude of possible topical and oral modalities, such as topical capsaicin, gabapentin, carbamazepine, oxcarbamazepine, cervical spine manipulation, anti-inflammatory medications, surgical rib resection, avoidance of sun exposure, and lamotrigine.1,3,5,12,20,21,27-32 Pruritus is a common symptom with a multitude of potential causes, some of which are never diagnosed. The absence of cutaneous signs makes diagnosis more difficult; however, the consistency of anatomic location and historical characteristics make the diagnosis of brachioradial pruritus possible. In addition, relief of pruritus with application of ice helps to confirm the diagnosis.10 A familial form of brachioradial pruritus was reported with a dominant and possible X-linked inheritance pattern.33 While an association between brachioradial pruritus and cervical spine disease is present, cervical spine disease alone cannot explain the pathophysiology of brachioradial pruritus. Furthermore, cervical spine disease undetectable by radiography may hinder a definitive understanding of this association. It is likely that both UV exposure and cervical spine disease contribute to this entity.

Brachioradial pruritus is an enigmatic entity characterized by pruritus localized to the skin overlying the proximal heads of the brachioradialis muscle, with few other clinical symptoms.1-5 It was first described by Waisman⁶ in 1968. Brachioradial pruritus characteristically affects middle-aged women residing in tropical to temperate climates, though it may occur in males and individuals residing in other climates.1-8 It often presents as tingling, burning pruritus on the dorsal aspect of the forearm. Pruritus may be unilateral or bilateral and may extend up the arm and across the upper back. It often is described as burning, stinging, or painful, and is seasonal in nature, often presenting in late summer and lasting into December.1-5 Brachioradial pruritus was originally associated with solar exposure and UV radiation. Later, Heyl9 proposed that cervical nerve root impingement or injury secondary to cervical trauma was causative. Although a true cause remains elusive, both actinic damage and cervical spine disease are likely involved. We discuss an otherwise healthy woman who presented with nonspecific pruritus consistent with brachioradial pruritus.

Case Report
A 46-year-old woman presented with persistent pruritus of the left proximal lateral forearm. The pruritus had been present for several years and was recalcitrant to a multitude of therapeutic modalities, including topical corticosteroids and oral antihistamines. Application of heat did not affect her symptoms; however, application of cold compresses did alleviate some of the pruritus. Her medical history was noncontributory. Her surgical history was pertinent for prior anterior cervical discectomy and fusion from C4 to C6. Physical examination revealed no obvious cutaneous lesions in the site other than mild erythema secondary to scratching. Magnetic resonance imaging of her cervical spine revealed a left-sided osteophyte causing minimal left neural foraminal stenosis at the level of C3 to C4 (Figure). Electromyography and nerve conduction velocity studies of the left upper extremity revealed a mildly prolonged left median sensory latency. The patient was treated with topical capsaicin cream with moderate success. She also was advised to avoid sun exposure to the affected area.

Comment
Brachioradial pruritus affects a focal circumscribed area of the proximal lateral forearm. The area typically involves a sun-exposed region and may include the forearm, arm, shoulder, neck, and/or upper thorax.2 Middle-aged women are most commonly affected, with tingling, burning, and pruritus of the affected area.1 Symptoms may last from August to December and may subside during the winter.1-5 Pruritus may be unilateral or bilateral. The nature of the pruritus is often described as burning, stinging, or painful, and manifests a seasonal relation, with high incidence in late summer corresponding with the highest UV exposure.1 Patients may report intensification of pruritus with scratching, which may be related to damage of peripheral nerve fibers.2,10 This intensification may, in part, be secondary to chronic UVA irradiation.11 Involvement of C fibers containing neuropeptides responsible for pruritus explains the rationale for treatment with topical capsaicin.2,5 Application of ice often is the only means of alleviating pruritus.10,12 The consistency of relief with ice is useful in the diagnostic screening of this entity.10 The neurophysiology of pruritus is not fully understood. However, it is known that Aδ and C fibers are responsible for the transmission of pruritus.9 Pruritus can be categorized as pruritoceptive (originating in the skin) or neurogenic (originating in the central nervous system), or a combination of both. The Aδ and C fibers are co-responsive to temperature change as well as pruritus. Increases in skin temperature lower the threshold of cutaneous pruritus receptor units.13 The neural pathway for pruritus has been established. Nociceptor C fibers transmit impulses to the dorsal horn of the spinal cord and then to the thalamus via the spinothalamic tract.14 Scratching typically relieves the sensation of pruritus.15 The gate-control theory postulates that afferent sensory input from cutaneous C fibers is modulated by a gate-control system at the level of the spinal cord.5,16,17 A subsequent Aδ impulse may act in a negative feedback method to shut off C-fiber stimulation. However, stimulation of Aδ fibers in brachioradial pruritus paradoxically seems to potentiate the sensation of pruritus.5 Wallengren5 suggested that local damage to peripheral nerve fibers could be responsible for this potentiation of pruritic sensation. Kumakiri et al18 demonstrated ultrastructural damage to dermal nerve fibers following UVA irradiation. UV radiation has been shown to cause a sensitizing effect on sensory nerve fibers and lower the threshold for sensory nerve stimulation, which may occur via direct effects of UV exposure or by release of neural mediators.19 The pathophysiology of brachioradial pruritus is controversial. The 2 proposed associations are UV exposure and cervical spine disease.20 Wallengren and Sundler2 proposed that solar-induced nerve injury is responsible for brachioradial pruritus. UV radiation may be an eliciting factor, while cervical spine disease may be a predisposing factor.2 On the contrary, Fisher21 reported on the association of cervical nerve root impingement and involvement of 1 or more of the C5 to C8 cervical nerve root segments. Brachioradial pruritus has been reported in association with an ependymoma and secondary to cervical nerve compression.9,22 In a report by Heyl,9 4 of 14 patients demonstrated evidence of degenerative changes and osteoarthritis between C4 and C7. In addition, Heyl9 noted that brachioradial pruritus may be caused by compression of structures not identified by cervical radiographs. In a series of 11 patients with brachioradial pruritus who underwent radiography of the spine, Goodkin et al12 found that all patients demonstrated radiographic abnormalities of the cervical spine. Magnetic resonance imaging is the most reliable diagnostic method for cervical nerve root compression.20,22 Recently, Crevits20 suggested that neural damage from peripheral nerves by solar radiation or local injury or from central sensory pathways, such as cervical spine disease, is a nonspecific cause. In view of the literature, a definitive pathophysiology for brachioradial pruritus does not exist. It is clear that it is a unique clinical entity, but the pathophysiologic basis is not known. While the association between cervical spine disease and brachioradial pruritus is not fully understood, the prevalence of cervical spine disease is higher in patients with brachioradial pruritus.12 It has not been determined if this association is causal or causative.20 A similar localized itch syndrome, notalgia paresthetica (NP), also has been examined with respect to cervical spine pathology.12,23-25 NP is similar to brachioradial pruritus but involves the dorsal spinal nerves. Savk et al23 found the presence of vertebral column pathology in 7 of 10 patients with NP. A subsequent larger study involving 43 patients with NP reported that in 34 patients (79%), spinal pathology had been detected by radiographs. Additionally, in 65% of patients (28/43), changes were most prominent in the vertebrae and corresponded to clinically involved dermatomes.24 However, not all pathologies are detectable via radiographic imaging.25 Thus, Savk and Savk25 reinforced the necessity of clinical and radiographic examination. Histologic examination is not necessary for the clinical diagnosis of brachioradial pruritus. Cutaneous biopsies most often demonstrate nonspecific findings and/or chronic solar damage. Wallengren and Sundler2 compared cutaneous biopsies in afflicted and control patients utilizing antibodies against a pan-neuronal marker, protein gene product 9.5, calcitonin gene-related peptide, and vanilloid receptor subtype 1 (VR1) for capsaicin-sensitive nerve structures. The number of protein gene product 9.5 immunoreative nerve fibers was reduced in pruritic skin by 23% to 43%.2 These findings suggest that brachioradial pruritus may be elicited by exposure to UV radiation and/or heat. Wallengren and Sundler2 noted one patient who relapsed with pruritus during the winter following use of a heating pad to relieve neck pain, which supports the notion that UV radiation and/or heat may be causative. Immunohistochemical studies demonstrated protein gene product 9.5 immunoreactive nerve fibers in a dense population in the epidermis and the dermis and calcitonin gene-related peptide immunoreactive nerve fibers located primarily in the dermis. Capsaicin-sensitive VR1 immunoreactive nerve fibers were located as free nerve fibers.2 Wallengren and Sundler2 proposed that the VR1 structures are associated with thermoreception. The reduction in nerve fibers via all markers in patients with brachioradial pruritus implicates their role. Furthermore, these histologic changes resemble those found in patients after serial phototherapy.2,26 Underlying cervical spine disease may amplify this pruritus. Treatment of brachioradial pruritus includes a multitude of possible topical and oral modalities, such as topical capsaicin, gabapentin, carbamazepine, oxcarbamazepine, cervical spine manipulation, anti-inflammatory medications, surgical rib resection, avoidance of sun exposure, and lamotrigine.1,3,5,12,20,21,27-32 Pruritus is a common symptom with a multitude of potential causes, some of which are never diagnosed. The absence of cutaneous signs makes diagnosis more difficult; however, the consistency of anatomic location and historical characteristics make the diagnosis of brachioradial pruritus possible. In addition, relief of pruritus with application of ice helps to confirm the diagnosis.10 A familial form of brachioradial pruritus was reported with a dominant and possible X-linked inheritance pattern.33 While an association between brachioradial pruritus and cervical spine disease is present, cervical spine disease alone cannot explain the pathophysiology of brachioradial pruritus. Furthermore, cervical spine disease undetectable by radiography may hinder a definitive understanding of this association. It is likely that both UV exposure and cervical spine disease contribute to this entity.

Brachioradial pruritus is an enigmatic entity characterized by pruritus localized to the skin overlying the proximal heads of the brachioradialis muscle, with few other clinical symptoms.1-5 It was first described by Waisman⁶ in 1968. Brachioradial pruritus characteristically affects middle-aged women residing in tropical to temperate climates, though it may occur in males and individuals residing in other climates.1-8 It often presents as tingling, burning pruritus on the dorsal aspect of the forearm. Pruritus may be unilateral or bilateral and may extend up the arm and across the upper back. It often is described as burning, stinging, or painful, and is seasonal in nature, often presenting in late summer and lasting into December.1-5 Brachioradial pruritus was originally associated with solar exposure and UV radiation. Later, Heyl9 proposed that cervical nerve root impingement or injury secondary to cervical trauma was causative. Although a true cause remains elusive, both actinic damage and cervical spine disease are likely involved. We discuss an otherwise healthy woman who presented with nonspecific pruritus consistent with brachioradial pruritus.

Case Report
A 46-year-old woman presented with persistent pruritus of the left proximal lateral forearm. The pruritus had been present for several years and was recalcitrant to a multitude of therapeutic modalities, including topical corticosteroids and oral antihistamines. Application of heat did not affect her symptoms; however, application of cold compresses did alleviate some of the pruritus. Her medical history was noncontributory. Her surgical history was pertinent for prior anterior cervical discectomy and fusion from C4 to C6. Physical examination revealed no obvious cutaneous lesions in the site other than mild erythema secondary to scratching. Magnetic resonance imaging of her cervical spine revealed a left-sided osteophyte causing minimal left neural foraminal stenosis at the level of C3 to C4 (Figure). Electromyography and nerve conduction velocity studies of the left upper extremity revealed a mildly prolonged left median sensory latency. The patient was treated with topical capsaicin cream with moderate success. She also was advised to avoid sun exposure to the affected area.

Comment
Brachioradial pruritus affects a focal circumscribed area of the proximal lateral forearm. The area typically involves a sun-exposed region and may include the forearm, arm, shoulder, neck, and/or upper thorax.2 Middle-aged women are most commonly affected, with tingling, burning, and pruritus of the affected area.1 Symptoms may last from August to December and may subside during the winter.1-5 Pruritus may be unilateral or bilateral. The nature of the pruritus is often described as burning, stinging, or painful, and manifests a seasonal relation, with high incidence in late summer corresponding with the highest UV exposure.1 Patients may report intensification of pruritus with scratching, which may be related to damage of peripheral nerve fibers.2,10 This intensification may, in part, be secondary to chronic UVA irradiation.11 Involvement of C fibers containing neuropeptides responsible for pruritus explains the rationale for treatment with topical capsaicin.2,5 Application of ice often is the only means of alleviating pruritus.10,12 The consistency of relief with ice is useful in the diagnostic screening of this entity.10 The neurophysiology of pruritus is not fully understood. However, it is known that Aδ and C fibers are responsible for the transmission of pruritus.9 Pruritus can be categorized as pruritoceptive (originating in the skin) or neurogenic (originating in the central nervous system), or a combination of both. The Aδ and C fibers are co-responsive to temperature change as well as pruritus. Increases in skin temperature lower the threshold of cutaneous pruritus receptor units.13 The neural pathway for pruritus has been established. Nociceptor C fibers transmit impulses to the dorsal horn of the spinal cord and then to the thalamus via the spinothalamic tract.14 Scratching typically relieves the sensation of pruritus.15 The gate-control theory postulates that afferent sensory input from cutaneous C fibers is modulated by a gate-control system at the level of the spinal cord.5,16,17 A subsequent Aδ impulse may act in a negative feedback method to shut off C-fiber stimulation. However, stimulation of Aδ fibers in brachioradial pruritus paradoxically seems to potentiate the sensation of pruritus.5 Wallengren5 suggested that local damage to peripheral nerve fibers could be responsible for this potentiation of pruritic sensation. Kumakiri et al18 demonstrated ultrastructural damage to dermal nerve fibers following UVA irradiation. UV radiation has been shown to cause a sensitizing effect on sensory nerve fibers and lower the threshold for sensory nerve stimulation, which may occur via direct effects of UV exposure or by release of neural mediators.19 The pathophysiology of brachioradial pruritus is controversial. The 2 proposed associations are UV exposure and cervical spine disease.20 Wallengren and Sundler2 proposed that solar-induced nerve injury is responsible for brachioradial pruritus. UV radiation may be an eliciting factor, while cervical spine disease may be a predisposing factor.2 On the contrary, Fisher21 reported on the association of cervical nerve root impingement and involvement of 1 or more of the C5 to C8 cervical nerve root segments. Brachioradial pruritus has been reported in association with an ependymoma and secondary to cervical nerve compression.9,22 In a report by Heyl,9 4 of 14 patients demonstrated evidence of degenerative changes and osteoarthritis between C4 and C7. In addition, Heyl9 noted that brachioradial pruritus may be caused by compression of structures not identified by cervical radiographs. In a series of 11 patients with brachioradial pruritus who underwent radiography of the spine, Goodkin et al12 found that all patients demonstrated radiographic abnormalities of the cervical spine. Magnetic resonance imaging is the most reliable diagnostic method for cervical nerve root compression.20,22 Recently, Crevits20 suggested that neural damage from peripheral nerves by solar radiation or local injury or from central sensory pathways, such as cervical spine disease, is a nonspecific cause. In view of the literature, a definitive pathophysiology for brachioradial pruritus does not exist. It is clear that it is a unique clinical entity, but the pathophysiologic basis is not known. While the association between cervical spine disease and brachioradial pruritus is not fully understood, the prevalence of cervical spine disease is higher in patients with brachioradial pruritus.12 It has not been determined if this association is causal or causative.20 A similar localized itch syndrome, notalgia paresthetica (NP), also has been examined with respect to cervical spine pathology.12,23-25 NP is similar to brachioradial pruritus but involves the dorsal spinal nerves. Savk et al23 found the presence of vertebral column pathology in 7 of 10 patients with NP. A subsequent larger study involving 43 patients with NP reported that in 34 patients (79%), spinal pathology had been detected by radiographs. Additionally, in 65% of patients (28/43), changes were most prominent in the vertebrae and corresponded to clinically involved dermatomes.24 However, not all pathologies are detectable via radiographic imaging.25 Thus, Savk and Savk25 reinforced the necessity of clinical and radiographic examination. Histologic examination is not necessary for the clinical diagnosis of brachioradial pruritus. Cutaneous biopsies most often demonstrate nonspecific findings and/or chronic solar damage. Wallengren and Sundler2 compared cutaneous biopsies in afflicted and control patients utilizing antibodies against a pan-neuronal marker, protein gene product 9.5, calcitonin gene-related peptide, and vanilloid receptor subtype 1 (VR1) for capsaicin-sensitive nerve structures. The number of protein gene product 9.5 immunoreative nerve fibers was reduced in pruritic skin by 23% to 43%.2 These findings suggest that brachioradial pruritus may be elicited by exposure to UV radiation and/or heat. Wallengren and Sundler2 noted one patient who relapsed with pruritus during the winter following use of a heating pad to relieve neck pain, which supports the notion that UV radiation and/or heat may be causative. Immunohistochemical studies demonstrated protein gene product 9.5 immunoreactive nerve fibers in a dense population in the epidermis and the dermis and calcitonin gene-related peptide immunoreactive nerve fibers located primarily in the dermis. Capsaicin-sensitive VR1 immunoreactive nerve fibers were located as free nerve fibers.2 Wallengren and Sundler2 proposed that the VR1 structures are associated with thermoreception. The reduction in nerve fibers via all markers in patients with brachioradial pruritus implicates their role. Furthermore, these histologic changes resemble those found in patients after serial phototherapy.2,26 Underlying cervical spine disease may amplify this pruritus. Treatment of brachioradial pruritus includes a multitude of possible topical and oral modalities, such as topical capsaicin, gabapentin, carbamazepine, oxcarbamazepine, cervical spine manipulation, anti-inflammatory medications, surgical rib resection, avoidance of sun exposure, and lamotrigine.1,3,5,12,20,21,27-32 Pruritus is a common symptom with a multitude of potential causes, some of which are never diagnosed. The absence of cutaneous signs makes diagnosis more difficult; however, the consistency of anatomic location and historical characteristics make the diagnosis of brachioradial pruritus possible. In addition, relief of pruritus with application of ice helps to confirm the diagnosis.10 A familial form of brachioradial pruritus was reported with a dominant and possible X-linked inheritance pattern.33 While an association between brachioradial pruritus and cervical spine disease is present, cervical spine disease alone cannot explain the pathophysiology of brachioradial pruritus. Furthermore, cervical spine disease undetectable by radiography may hinder a definitive understanding of this association. It is likely that both UV exposure and cervical spine disease contribute to this entity.

Dermatitis herpetiformis (DH) is a chronic pruritic cutaneous eruption associated with gluten-sensitive enteropathy (celiac disease [CD]) and immunoglobulin A (IgA) deposition in the skin. While the disease is not uncommon among adolescents, DH is rarely seen in prepubertal patients. Children with DH present similarly to adults; however, uncommon skin findings have been reported. Because of an increased risk for autoimmune diseases and lymphoma, accurate diagnosis and treatment are imperative. We present a case of DH in a 6-year-old Latino boy previously diagnosed with atopic dermatitis and recurrent urticaria. Our aim is to highlight the various cutaneous presentations of DH and encourage clinicians to consider this diagnosis in young patients with recalcitrant atypical skin disease.
Case Report
A 6-year-old Latino boy presented with a history of pruritic skin lesions (beginning at the age of 9 months) previously diagnosed as atopic dermatitis and recurrent urticaria. His pediatrician prescribed topical steroids and oral diphenhydramine hydrochloride, without improvement. On examination, the patient had few excoriated edematous papules on his buttocks (Figure 1) and urticarial plaques on his upper extremity. His skin was xerotic but lacked any lichenified plaques or papules in the antecubital and popliteal fossae. The patient denied any associated nausea or diarrhea. Family history was negative for atopy and autoimmune disease. The mother reported that the patient was, at one time, "small for his age" but is now closer in size to his peers.

A punch biopsy was obtained from an urticarial plaque on his arm and treatment was initiated with desonide cream 0.05% twice daily to the affected areas. The biopsy revealed collections of neutrophils in the papillary dermis as well as clefting at the dermoepidermal junction (Figure 2). A second biopsy for direct immunofluorescence (DIF) was performed from perilesional gluteal skin. This specimen exhibited granular immunoglobulin A (IgA) deposits in the papillary dermis, thus confirming the diagnosis of dermatitis herpetiformis (DH).

Evaluation by a gastroenterologist who performed serologic testing and endoscopic biopsy of the small intestine further substantiated the diagnosis. In the serum, the presence of immunoglobulin G antigliadin (42.3 U/mL; reference, 100 U/mL; reference, <10), IgA anti–tissue transglutaminase (anti-tTGase)(>100 U/mL; reference, <4), and IgA antiendomysial (positive; reference, negative) antibodies were detected. The intestinal biopsy revealed villous atrophy accompanied by duodenitis consistent with celiac disease (CD). HLA typing was not performed. A complete blood count with differential blood count, comprehensive metabolic panel, thyroxine, thyroid stimulating hormone, and thyroglobulin antibodies were all within reference range. The patient was initiated on a gluten-free diet and subsequently developed fewer lesions and reduced pruritus.

Comment

DH is a cutaneous manifestation of CD, which is an immune-mediated enteropathy caused by gluten sensitivity. The symptoms of childhood CD include persistent diarrhea, failure to thrive, abdominal pain, and vomiting. Iron deficiency anemia also may be present as well as other sequelae of malabsorption. Although patients with DH usually do not have gastrointestinal symptoms, virtually all patients with DH show evidence of the same gluten-sensitive enteropathy of the small bowel.
Gluten is a grain protein found in wheat, barley, and rye, but not in oats. Gliadin, the alcohol-soluble fraction of gluten, is believed to be the inciting stimulus.1 In addition to antigliadin antibodies, patients with DH have circulating antiendomysial and antitransglutaminase antibodies with uncertain roles in pathogenesis. The prevailing theory suggests that gluten sensitivity leads to the formation of IgA antibodies to gluten-transglutaminase complexes. These antibodies cross-react with other transglutaminases, specifically epidermal transglutaminase, which is highly homologous. Deposition of IgA–transglutaminase 3 complexes within the papillary dermis cause skin lesions of DH.2,3
Childhood DH is rare, with an uncertain incidence and prevalence. Cases have been reported in children as young as 8 months,4 but most children receive the diagnosis between the ages of 2 and 7 years.5 DH is most prevalent in individuals of Northern European descent. In adults, men with DH outnumber women by a ratio of nearly 2:16; however, among childhood cases, there is a female predominance.5,7 A genetic predisposition for gluten sensitivity is supported by the high prevalence of DH and CD among first-degree relatives of known patients with DH and CD as well as a documented HLA association. The DQ2 and DQ8 alleles are most closely linked with DH and CD.8
The clinical presentation of DH is characterized by symmetrically distributed papulovesicular lesions and urticarial plaques, often favoring the back, buttocks, and extensor surfaces of the extremities. Because the lesions are intensely pruritic, intact vesicles are rarely observed by the clinician. Children, by most accounts, present similarly to adults; however, uncommon skin findings may be present and include isolated involvement of the palms,9 hemorrhagic lesions of the palms and soles,10 deep dermal papules and nodules,11 and facial lesions.5,11 Powell et al12 described a case with a predominance of urticarial lesions. Thus, childhood DH often is misdiagnosed as atopic dermatitis, papular urticaria, scabies, linear IgA dermatosis, or chronic urticaria. Recalcitrant cases of these diseases or patients who present with atypical findings of common diseases like atopic dermatitis should prompt the clinician to consider DH in the differential diagnosis.
The gold standard for diagnosing DH is DIF of a biopsy from perilesional skin, which shows granular IgA deposits most often localized to the papillary dermis. For routine histology, a biopsy of an intact vesicle is preferred where neutrophils in the papillary dermis and clefting at the dermoepidermal junction are seen. Although granular IgA deposits seen on DIF are highly specific for DH, up to 10% of cases may have a negative DIF.13,14 To confirm the diagnosis, serologic testing for anti-tTGase antibodies is useful. Using an enzyme-linked immunosorbent assay, tTGase antibodies can be detected in serum with specificity and sensitivity above 90% for patients on normal diets.15,16 Desai et al17 documented the cost-effectiveness of enzyme-linked immunosorbent assay tTGase testing and proposed that serologic testing be used primarily in the diagnosis of DH. Once patients remove gluten from their diet, the skin lesions and enteropathy resolve. Furthermore, tTGase antibodies decrease to levels within reference range in the absence of gluten; thus, serologic testing can be used to monitor dietary compliance.
Patients with DH are at higher risk for autoimmune diseases, particularly Hashimoto thyroiditis, pernicious anemia, and type 1 diabetes mellitus, among others.18-20 The association between DH and lymphoma, mostly T-cell lymphoma, is well-documented, with 78% of lymphomas arising from the small bowel, thus warranting vigilant surveillance and regular follow-up with a gastroenterologist.21 Lewis et al,22 in a retrospective study of 487 patients with DH, found that lymphoma only occurred in patients not on gluten-free diets or in patients who had followed the gluten-free diet for less than 5 years. Moreover, patients in this study who did adhere to the gluten-free diet had no increased risk for developing lymphoma over the general population.22
The primary treatment of DH is a gluten-free diet that is protective against the development of lymphoma. Dietary compliance is challenging, especially for children; therefore, referral to a dietician familiar with this area is helpful. Because months of dietary restriction are needed before a response is noted, many patients require pharmacologic treatment with dapsone. The recommended starting dose for children is 2 mg/kg daily with titration based on clinical response.23 Most patients will have a rapid response to dapsone within 48 to 72 hours. However, the enteropathy is unaffected by dapsone therapy and patients should be encouraged to maintain dietary compliance.

Conclusion

Childhood DH is rare and can present with atypical lesions involving the palms and soles, urticarial lesions, deep dermal papules and nodules, and facial lesions. If aware of these unusual presentations, clinicians may consider the diagnosis of DH and act to further evaluate cases of suspected common diseases not responding to treatment.

Dermatitis herpetiformis (DH) is a chronic pruritic cutaneous eruption associated with gluten-sensitive enteropathy (celiac disease [CD]) and immunoglobulin A (IgA) deposition in the skin. While the disease is not uncommon among adolescents, DH is rarely seen in prepubertal patients. Children with DH present similarly to adults; however, uncommon skin findings have been reported. Because of an increased risk for autoimmune diseases and lymphoma, accurate diagnosis and treatment are imperative. We present a case of DH in a 6-year-old Latino boy previously diagnosed with atopic dermatitis and recurrent urticaria. Our aim is to highlight the various cutaneous presentations of DH and encourage clinicians to consider this diagnosis in young patients with recalcitrant atypical skin disease.
Case Report
A 6-year-old Latino boy presented with a history of pruritic skin lesions (beginning at the age of 9 months) previously diagnosed as atopic dermatitis and recurrent urticaria. His pediatrician prescribed topical steroids and oral diphenhydramine hydrochloride, without improvement. On examination, the patient had few excoriated edematous papules on his buttocks (Figure 1) and urticarial plaques on his upper extremity. His skin was xerotic but lacked any lichenified plaques or papules in the antecubital and popliteal fossae. The patient denied any associated nausea or diarrhea. Family history was negative for atopy and autoimmune disease. The mother reported that the patient was, at one time, "small for his age" but is now closer in size to his peers.

A punch biopsy was obtained from an urticarial plaque on his arm and treatment was initiated with desonide cream 0.05% twice daily to the affected areas. The biopsy revealed collections of neutrophils in the papillary dermis as well as clefting at the dermoepidermal junction (Figure 2). A second biopsy for direct immunofluorescence (DIF) was performed from perilesional gluteal skin. This specimen exhibited granular immunoglobulin A (IgA) deposits in the papillary dermis, thus confirming the diagnosis of dermatitis herpetiformis (DH).

Evaluation by a gastroenterologist who performed serologic testing and endoscopic biopsy of the small intestine further substantiated the diagnosis. In the serum, the presence of immunoglobulin G antigliadin (42.3 U/mL; reference, 100 U/mL; reference, <10), IgA anti–tissue transglutaminase (anti-tTGase)(>100 U/mL; reference, <4), and IgA antiendomysial (positive; reference, negative) antibodies were detected. The intestinal biopsy revealed villous atrophy accompanied by duodenitis consistent with celiac disease (CD). HLA typing was not performed. A complete blood count with differential blood count, comprehensive metabolic panel, thyroxine, thyroid stimulating hormone, and thyroglobulin antibodies were all within reference range. The patient was initiated on a gluten-free diet and subsequently developed fewer lesions and reduced pruritus.

Comment

DH is a cutaneous manifestation of CD, which is an immune-mediated enteropathy caused by gluten sensitivity. The symptoms of childhood CD include persistent diarrhea, failure to thrive, abdominal pain, and vomiting. Iron deficiency anemia also may be present as well as other sequelae of malabsorption. Although patients with DH usually do not have gastrointestinal symptoms, virtually all patients with DH show evidence of the same gluten-sensitive enteropathy of the small bowel.
Gluten is a grain protein found in wheat, barley, and rye, but not in oats. Gliadin, the alcohol-soluble fraction of gluten, is believed to be the inciting stimulus.1 In addition to antigliadin antibodies, patients with DH have circulating antiendomysial and antitransglutaminase antibodies with uncertain roles in pathogenesis. The prevailing theory suggests that gluten sensitivity leads to the formation of IgA antibodies to gluten-transglutaminase complexes. These antibodies cross-react with other transglutaminases, specifically epidermal transglutaminase, which is highly homologous. Deposition of IgA–transglutaminase 3 complexes within the papillary dermis cause skin lesions of DH.2,3
Childhood DH is rare, with an uncertain incidence and prevalence. Cases have been reported in children as young as 8 months,4 but most children receive the diagnosis between the ages of 2 and 7 years.5 DH is most prevalent in individuals of Northern European descent. In adults, men with DH outnumber women by a ratio of nearly 2:16; however, among childhood cases, there is a female predominance.5,7 A genetic predisposition for gluten sensitivity is supported by the high prevalence of DH and CD among first-degree relatives of known patients with DH and CD as well as a documented HLA association. The DQ2 and DQ8 alleles are most closely linked with DH and CD.8
The clinical presentation of DH is characterized by symmetrically distributed papulovesicular lesions and urticarial plaques, often favoring the back, buttocks, and extensor surfaces of the extremities. Because the lesions are intensely pruritic, intact vesicles are rarely observed by the clinician. Children, by most accounts, present similarly to adults; however, uncommon skin findings may be present and include isolated involvement of the palms,9 hemorrhagic lesions of the palms and soles,10 deep dermal papules and nodules,11 and facial lesions.5,11 Powell et al12 described a case with a predominance of urticarial lesions. Thus, childhood DH often is misdiagnosed as atopic dermatitis, papular urticaria, scabies, linear IgA dermatosis, or chronic urticaria. Recalcitrant cases of these diseases or patients who present with atypical findings of common diseases like atopic dermatitis should prompt the clinician to consider DH in the differential diagnosis.
The gold standard for diagnosing DH is DIF of a biopsy from perilesional skin, which shows granular IgA deposits most often localized to the papillary dermis. For routine histology, a biopsy of an intact vesicle is preferred where neutrophils in the papillary dermis and clefting at the dermoepidermal junction are seen. Although granular IgA deposits seen on DIF are highly specific for DH, up to 10% of cases may have a negative DIF.13,14 To confirm the diagnosis, serologic testing for anti-tTGase antibodies is useful. Using an enzyme-linked immunosorbent assay, tTGase antibodies can be detected in serum with specificity and sensitivity above 90% for patients on normal diets.15,16 Desai et al17 documented the cost-effectiveness of enzyme-linked immunosorbent assay tTGase testing and proposed that serologic testing be used primarily in the diagnosis of DH. Once patients remove gluten from their diet, the skin lesions and enteropathy resolve. Furthermore, tTGase antibodies decrease to levels within reference range in the absence of gluten; thus, serologic testing can be used to monitor dietary compliance.
Patients with DH are at higher risk for autoimmune diseases, particularly Hashimoto thyroiditis, pernicious anemia, and type 1 diabetes mellitus, among others.18-20 The association between DH and lymphoma, mostly T-cell lymphoma, is well-documented, with 78% of lymphomas arising from the small bowel, thus warranting vigilant surveillance and regular follow-up with a gastroenterologist.21 Lewis et al,22 in a retrospective study of 487 patients with DH, found that lymphoma only occurred in patients not on gluten-free diets or in patients who had followed the gluten-free diet for less than 5 years. Moreover, patients in this study who did adhere to the gluten-free diet had no increased risk for developing lymphoma over the general population.22
The primary treatment of DH is a gluten-free diet that is protective against the development of lymphoma. Dietary compliance is challenging, especially for children; therefore, referral to a dietician familiar with this area is helpful. Because months of dietary restriction are needed before a response is noted, many patients require pharmacologic treatment with dapsone. The recommended starting dose for children is 2 mg/kg daily with titration based on clinical response.23 Most patients will have a rapid response to dapsone within 48 to 72 hours. However, the enteropathy is unaffected by dapsone therapy and patients should be encouraged to maintain dietary compliance.

Conclusion

Childhood DH is rare and can present with atypical lesions involving the palms and soles, urticarial lesions, deep dermal papules and nodules, and facial lesions. If aware of these unusual presentations, clinicians may consider the diagnosis of DH and act to further evaluate cases of suspected common diseases not responding to treatment.

Dermatitis herpetiformis (DH) is a chronic pruritic cutaneous eruption associated with gluten-sensitive enteropathy (celiac disease [CD]) and immunoglobulin A (IgA) deposition in the skin. While the disease is not uncommon among adolescents, DH is rarely seen in prepubertal patients. Children with DH present similarly to adults; however, uncommon skin findings have been reported. Because of an increased risk for autoimmune diseases and lymphoma, accurate diagnosis and treatment are imperative. We present a case of DH in a 6-year-old Latino boy previously diagnosed with atopic dermatitis and recurrent urticaria. Our aim is to highlight the various cutaneous presentations of DH and encourage clinicians to consider this diagnosis in young patients with recalcitrant atypical skin disease.
Case Report
A 6-year-old Latino boy presented with a history of pruritic skin lesions (beginning at the age of 9 months) previously diagnosed as atopic dermatitis and recurrent urticaria. His pediatrician prescribed topical steroids and oral diphenhydramine hydrochloride, without improvement. On examination, the patient had few excoriated edematous papules on his buttocks (Figure 1) and urticarial plaques on his upper extremity. His skin was xerotic but lacked any lichenified plaques or papules in the antecubital and popliteal fossae. The patient denied any associated nausea or diarrhea. Family history was negative for atopy and autoimmune disease. The mother reported that the patient was, at one time, "small for his age" but is now closer in size to his peers.

A punch biopsy was obtained from an urticarial plaque on his arm and treatment was initiated with desonide cream 0.05% twice daily to the affected areas. The biopsy revealed collections of neutrophils in the papillary dermis as well as clefting at the dermoepidermal junction (Figure 2). A second biopsy for direct immunofluorescence (DIF) was performed from perilesional gluteal skin. This specimen exhibited granular immunoglobulin A (IgA) deposits in the papillary dermis, thus confirming the diagnosis of dermatitis herpetiformis (DH).

Evaluation by a gastroenterologist who performed serologic testing and endoscopic biopsy of the small intestine further substantiated the diagnosis. In the serum, the presence of immunoglobulin G antigliadin (42.3 U/mL; reference, 100 U/mL; reference, <10), IgA anti–tissue transglutaminase (anti-tTGase)(>100 U/mL; reference, <4), and IgA antiendomysial (positive; reference, negative) antibodies were detected. The intestinal biopsy revealed villous atrophy accompanied by duodenitis consistent with celiac disease (CD). HLA typing was not performed. A complete blood count with differential blood count, comprehensive metabolic panel, thyroxine, thyroid stimulating hormone, and thyroglobulin antibodies were all within reference range. The patient was initiated on a gluten-free diet and subsequently developed fewer lesions and reduced pruritus.

Comment

DH is a cutaneous manifestation of CD, which is an immune-mediated enteropathy caused by gluten sensitivity. The symptoms of childhood CD include persistent diarrhea, failure to thrive, abdominal pain, and vomiting. Iron deficiency anemia also may be present as well as other sequelae of malabsorption. Although patients with DH usually do not have gastrointestinal symptoms, virtually all patients with DH show evidence of the same gluten-sensitive enteropathy of the small bowel.
Gluten is a grain protein found in wheat, barley, and rye, but not in oats. Gliadin, the alcohol-soluble fraction of gluten, is believed to be the inciting stimulus.1 In addition to antigliadin antibodies, patients with DH have circulating antiendomysial and antitransglutaminase antibodies with uncertain roles in pathogenesis. The prevailing theory suggests that gluten sensitivity leads to the formation of IgA antibodies to gluten-transglutaminase complexes. These antibodies cross-react with other transglutaminases, specifically epidermal transglutaminase, which is highly homologous. Deposition of IgA–transglutaminase 3 complexes within the papillary dermis cause skin lesions of DH.2,3
Childhood DH is rare, with an uncertain incidence and prevalence. Cases have been reported in children as young as 8 months,4 but most children receive the diagnosis between the ages of 2 and 7 years.5 DH is most prevalent in individuals of Northern European descent. In adults, men with DH outnumber women by a ratio of nearly 2:16; however, among childhood cases, there is a female predominance.5,7 A genetic predisposition for gluten sensitivity is supported by the high prevalence of DH and CD among first-degree relatives of known patients with DH and CD as well as a documented HLA association. The DQ2 and DQ8 alleles are most closely linked with DH and CD.8
The clinical presentation of DH is characterized by symmetrically distributed papulovesicular lesions and urticarial plaques, often favoring the back, buttocks, and extensor surfaces of the extremities. Because the lesions are intensely pruritic, intact vesicles are rarely observed by the clinician. Children, by most accounts, present similarly to adults; however, uncommon skin findings may be present and include isolated involvement of the palms,9 hemorrhagic lesions of the palms and soles,10 deep dermal papules and nodules,11 and facial lesions.5,11 Powell et al12 described a case with a predominance of urticarial lesions. Thus, childhood DH often is misdiagnosed as atopic dermatitis, papular urticaria, scabies, linear IgA dermatosis, or chronic urticaria. Recalcitrant cases of these diseases or patients who present with atypical findings of common diseases like atopic dermatitis should prompt the clinician to consider DH in the differential diagnosis.
The gold standard for diagnosing DH is DIF of a biopsy from perilesional skin, which shows granular IgA deposits most often localized to the papillary dermis. For routine histology, a biopsy of an intact vesicle is preferred where neutrophils in the papillary dermis and clefting at the dermoepidermal junction are seen. Although granular IgA deposits seen on DIF are highly specific for DH, up to 10% of cases may have a negative DIF.13,14 To confirm the diagnosis, serologic testing for anti-tTGase antibodies is useful. Using an enzyme-linked immunosorbent assay, tTGase antibodies can be detected in serum with specificity and sensitivity above 90% for patients on normal diets.15,16 Desai et al17 documented the cost-effectiveness of enzyme-linked immunosorbent assay tTGase testing and proposed that serologic testing be used primarily in the diagnosis of DH. Once patients remove gluten from their diet, the skin lesions and enteropathy resolve. Furthermore, tTGase antibodies decrease to levels within reference range in the absence of gluten; thus, serologic testing can be used to monitor dietary compliance.
Patients with DH are at higher risk for autoimmune diseases, particularly Hashimoto thyroiditis, pernicious anemia, and type 1 diabetes mellitus, among others.18-20 The association between DH and lymphoma, mostly T-cell lymphoma, is well-documented, with 78% of lymphomas arising from the small bowel, thus warranting vigilant surveillance and regular follow-up with a gastroenterologist.21 Lewis et al,22 in a retrospective study of 487 patients with DH, found that lymphoma only occurred in patients not on gluten-free diets or in patients who had followed the gluten-free diet for less than 5 years. Moreover, patients in this study who did adhere to the gluten-free diet had no increased risk for developing lymphoma over the general population.22
The primary treatment of DH is a gluten-free diet that is protective against the development of lymphoma. Dietary compliance is challenging, especially for children; therefore, referral to a dietician familiar with this area is helpful. Because months of dietary restriction are needed before a response is noted, many patients require pharmacologic treatment with dapsone. The recommended starting dose for children is 2 mg/kg daily with titration based on clinical response.23 Most patients will have a rapid response to dapsone within 48 to 72 hours. However, the enteropathy is unaffected by dapsone therapy and patients should be encouraged to maintain dietary compliance.

Conclusion

Childhood DH is rare and can present with atypical lesions involving the palms and soles, urticarial lesions, deep dermal papules and nodules, and facial lesions. If aware of these unusual presentations, clinicians may consider the diagnosis of DH and act to further evaluate cases of suspected common diseases not responding to treatment.