Dermatitis Herpetiformis_0414 Derm Look 1
Neurotic Excoriation_0414 Derm Look 2
A white woman, aged 36 years, presented with a severely pruritic eruption on her upper and lower extremities and on her lower back. The rash had been present for six months and tended to wax and wane with no alleviating or aggravating factors.
Erythematous excoriated papules were noted on bilateral extensor forearms, elbows, lower back, buttocks, and knees. Hypopigmented macules were appreciated in a similar distribution. Medical history was significant for celiac disease, and the woman admitted having trouble adhering to a gluten-free diet.
A 41-year-old woman sought treatment for a severely pruritic rash that had been present for eight months. Excoriated papules and linear erosions were appreciated on bilateral upper- and lower-extensor extremities and upper back. Hyperpigmented and hypopigmented macules were present in a similar distribution.
The woman had been seen by her primary-care clinician and had no evidence of renal or liver disease and was up to date on age-appropriate cancer screening. No household contacts had symptoms of pruritus or a similar rash.
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CASE #1: Dermatitis herpetiformis
Dermatitis herpetiformis (DH) is a cutaneous manifestation of celiac disease. The skin disease was first described in 1884, but it was not until 1967 that the association between DH and celiac disease was discovered. Approximately 90% of patients will have evidence of a gluten-sensitive enteropathy on pathologic examination of the small intestine. However, only 20% of patients with DH will have GI symptoms of celiac disease.1
Nearly 90% of persons with DH and celiac disease have the HLA class II DQ2 genotype or, less commonly, the DQ8 genotype, suggesting a strong genetic association. A Utah-based study conducted in 1987 found the prevalence to be 11.2 per 100,000 and the incidence to be 0.98 per 100,000 per year.2 DH is seen more commonly in individuals who are of northern European descent. The mean age of onset of the disease is in the fourth decade, and male patients outnumber female patients by a ratio of 2:1.
Dietary wheat is digested into gliadin peptides, which are then transported across the GI mucosal epithelium. Within the GI tract, tissue transglutaminase deamidates glutamine residues within gliadin peptides to glutamic acid. Tissue transglutaminase may also become covalently cross-linked to the gliadin peptides, which results in the production of cytokines and matrix metalloproteinases that cause GI epithelial cell damage.
Tissue transglutaminase-specific B cells present gliadin peptides to helper T cells, which stimulate the B cells to produce anti-tissue transglutaminase immunoglobulin (Ig)A antibodies. These anti-tissue transglutaminase antibodies cross-react with epidermal transglutaminase, and immune complexes form.
The immune complexes lead to granular IgA deposition within the dermal papillae. This deposition, in turn, leads to neutrophil chemotaxis, proteolytic cleavage of the weakest part of the basement membrane (lamina lucida), and subepidermal blister development.
Primary lesions of DH present as erythematous urticarial papules, plaques, and/or vesicles. Grouped vesicles often appear on an erythematous base; hence the term herpetiform. Patients with DH tend to have intense pruritus, and by the time they present to the clinician, the lesions are secondarily excoriated and crusted. When this occurs, the characteristic distribution of the lesions on the posterior neck, elbows, extensor forearms, back, buttocks, and knees help alert the clinician to the diagnosis.
The best histologic lesions are seen when biopsies are taken from erythematous skin adjacent to the vesicles. Histologically, DH forms subepidermal bullae with neutrophilic microabscesses that congregate in the dermal papillae. Early lesions of DH are multiloculated. However, as the separation between the tips of the dermal papillae and overlying epidermis become more severe, the lesions become unilocular.
Direct immunofluorescence (DIF) of adjacent nonaffected skin will show granular IgA deposition within the dermal papillae. A strict gluten-free diet may result in the disappearance of IgA from within the skin. However, the presence of IgA is not altered by dapsone therapy.
Other blistering disorders, such as linear IgA, bullous pemphigoid (BP), and bullous lupus erythematosus, may be considered in the differential diagnosis.
Clinically, linear IgA presents as small vesicles or large bullae. Histologically, linear IgA may appear similar to DH as subepidermal bullae with neutrophils. However, on DIF, and linear IgA features fine linear IgA deposition along the basement membrane zone, in contrast to the granular IgA deposition within the dermal papilla of DH.
Patients with BP present with large tense bullae on the trunk and extremities. Histologically, subepidermal bullae with eosinophils are present, linear IgG and complement component 3 (C3) are seen along the basement membrane zone on DIF.
Bullous lupus erythematosus may also have a histologic picture that is similar to DH and linear IgA. However, patients often have clinical and serologic (i.e., positive antinuclear antibody) features of systemic lupus erythematosus, and DIF reveals multiple immunoglobulins in a granular and bandlike pattern along the basement membrane zone. Given the characteristic involvement of extensor surfaces, erythema multiforme may also be considered. Since the lesions are often excoriated at the time of presentation, the diagnosis of scabies, arthropod bite, and/or neurotic excoriations may be entertained.
The cutaneous manifestations of the disease improve after implementing a gluten-free diet and/or therapy with dapsone. Typically within 48 hours of dapsone therapy, the pruritic skin lesions of DH improve. However, while GI symptoms resolve quickly with gluten avoidance, skin lesions may take up to two years to dissipate.3 The initial dosage of dapsone is usually 25 mg to 50 mg for adults, and the average maintenance dose is 100 mg. The dose should be tapered to the minimal effective dose with a goal of one to two new lesions per week. Increasing the dapsone dose beyond that only increase the toxicity with little cutaneous benefit.
Other autoimmune disorders may also be associated with DH, most commonly diabetes mellitus or thyroid disease, specifically Hashimoto thyroiditis. Patients with celiac disease are also at an increased risk of developing an enteropathy-associated T-cell lymphoma. Implementing gluten avoidance may decrease this risk. However, recent studies have shown that those with both celiac disease and DH may not be at an increased risk for developing lymphoma.4 Interestingly, patients with DH tend to have a milder degree of villous atrophy in the GI tract when compared with those with frank celiac disease; this is hypothesized to account for the decreased risk of lymphoma.4
Given the intense pruritus and desire for immediate relief, the woman in this case was treated with dapsone. She was also encouraged to avoid gluten. She continues to have regular follow-up with her gastroenterologist for celiac disease. Evaluation for diabetes mellitus and thyroid disease was negative.
CASE #2: Neurotic excoriation
Neurotic excoriation, also known as psychogenic excoriation, describes a condition in which a patient has the excessive fixation to pick at his or her normal or seemingly normal skin. Eventually, the tendency becomes so persistent that one makes excoriations of the skin.
Some people have the episodic or continuous desire to unconsciously pick at such irregularities as acne, arthropod bites, or keratin plugs, and this is considered a simple habit. In contrast, patients with neurotic excoriations consciously and uncontrollably have the desire to pick or scratch at their skin, causing characteristic lesions.
The excessive desire to pick or scratch may happen as the hand notices an irregularity on the skin, or it may occur in a ritualistic fashion. Unlike such other self-inflicted dermatoses as dermatitis artefacta and malingering, patients with neurotic excoriation acknowledge the self-inflicted nature of the lesions.
Because there is no underlying pathology in the skin, neurotic excoriation may be best understood as a psychological process with dermatologic manifestations. The most common psychopathologies associated with the disorder include depression, bipolar disorder, stress, anxiety, and obsessive-compulsive disorder.5
The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), estimates that the lifetime prevalence of excoriation disorder is at least 1.4% in the general population.6 It has also been estimated that approximately three-fourths of these patients are females. While the disorder may occur at any age, the most severe cases start in the third to fifth decades.6
The DSM-5 places excoriation (skin-picking) disorder in the category of obsessive-compulsive and related disorders. The specific criteria for the disorder are the following:
- Recurrent skin-picking, resulting in skin lesions
- Repeated attempts to decrease or stop skin-picking
- The skin-picking causes clinically significant distress or impairment in social, occupational, or other important areas of functioning
- The skin-picking cannot be attributed to the physiologic effects of a substance or other medical condition
- The skin-picking cannot be better explained by the symptoms of another mental disorder (eg, delusions or tactile hallucinations [psychotic disorder], attempts to improve a perceived defect or flaw in one’s appearance [body dysmorphic disorder], sterotypies [stereotypic movement disorder], or intention to harm oneself [nonsuicidal self-injury]).6
The self-inflicted excoriations are characterized as superficial or deep erosions that are clean-based or covered with a scab. The erosions are often linear and are usually of similar size and shape but at various stages of healing.
Hypopigmented or hyperpigmented macules represent healed erosions and are also appreciated among the active excoriations. The most commonly affected body sites include the face, the upper back, and the extensor surfaces of the extremities.
Persons with neurotic excoriations may best be divided into two categories: those with primarily facial disease and those with primarily body disease. Those with primarily facial disease are said to have acne excoriée.
Patients often have the uncontrollable desire to manipulate acne. Those with primarily body disease present with characteristic lesions located on the accessible upper back and the extensor surfaces of the extremities.
When a patient presents with neurotic excoriations, the clinician must rule out arthropod bites, dermatitis herpetiformis, folliculitis, lymphoma, delusions of parasitosis, and other obvious dermatologic or medical explanations for pruritus.
The appropriate workup is indicated by the patient’s history. Histologically, epidermal ulceration with a mild superficial mixed infiltrate is often appreciated. Older lesions may demonstrate dermal scar tissue and/or changes of lichen simplex chronicus.
Patients with acne excoriée are best treated with acne medications and encouraged to avoid manipulation of the acne lesions. For those afflicted by primarily body disease, treatment is based on symptom severity. When pruritus is severe, such topical antipruritics as doxepin 5% cream (Prudoxin, Zonalon) or lotions containing pramoxine or menthol and phenol may provide relief.
Such antihistamines as diphenhydramine or hydroxyzine (Vistaril) may provide sedative and antipruritic therapy. Doxepin cream is often a treatment of choice because of its antidepressant and antipruritic effects.
In 2005, Kirshnan and Koo reported that pathology of the central nervous system and the opioid neurotransmitter system are the basis for neurotic excoriations.7 This report led to the suggestion that psychiatric medications could be used to treat the condition. Such selective serotonin reuptake inhibitors as paroxetine (Paxil), fluoxetine (Prozac, Rapiflux, Sarafem, Selfemra), and sertraline (Zoloft) have demonstrated efficacy in the treatment of neurotic excoriation.8
Other psychiatric medications that have been employed include clomipramine (Anafranil), desipramine (Norpramin), olanzapine (Zyprexa), lithium (Lithobid), buspirone (BuSpar), and quick-acting benzodiazepines.8 All treatments for neurotic excoriation are off-label.
A mental health professional can help to teach the patient diversion strategies to avoid picking at the lesions. In all cases of neurotic excoriation, the clinician, the patient, and the psychiatrist and/or psychologist should work together as a team to provide the best possible therapeutic approach.
Neurotic excoriation can be controlled if the underlying psychological illness is effectively treated. However, patients frequently have difficulty abstaining from the habit of picking. Without proper medical and psychiatric treatment, the disorder tends to be a chronic condition and can result in significant scarring.
This woman was treated with doxepin as well as with a menthol/phenol lotion. She was also referred to psychiatry.
Kerri Robbins, MD, is an instructor in the Department of Dermatology at Baylor College of Medicine in Houston.
HOW TO TAKE THE POST-TEST: This Clinical Advisor CME activity consists of 3 articles. To obtain credit, you must also read Hyperpigmented patches on the back and Yellow scalp patches with mild scaling. Then take the post-test here .
- Alonso-Llamazares J, Gibson LE, Rogers RS 3rd. Clinical, pathologic, and immunopathologic features of dermatitis herpetiformis: review of the Mayo Clinic experience. Int J Dermatol. 2007;46:910-919.
- Smith JB, Tulloch JE, Meyer LJ, et al. The incidence and prevalence of dermatitis herpetiformis in Utah. Arch Dermatol. 1992;128:1608-1610.
- Thrash B, Patel M, Shah KR, et al. Cutaneous manifestations of gastrointestinal disease: part II. J Am Acad Dermatol. 2013;68:211.e1-33.
- Lewis HM, Renaula TL, Garioch JJ, et al. Protective effect of gluten-free diet against development of lymphoma in dermatitis herpetiformis. Br J Dermatol. 1996;135:363-367.
- Brodin MB. Neurotic excoriations. J Am Acad Dermatol. 2010;63:341-242.
- American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Arlington, Va.: American Psychiatric Association; 2013:254-7.
- Krishnan A, Koo J. Psyche, opioids, and itch: therapeutic consequences. Dermatol Ther. 2005;18:314-322.
- Arnold LM, Auchenbach MG, McElroy SL. Psychogenic excoriation. Clinical features, proposed diagnostic criteria, epidemiology and approaches to treatment. CNS Drugs. 2001;15:351-359.