Continuing Education Activity

Schamberg disease is the most frequent purpuric of the dermatoses, with a classical presentation characterized by petechiae, purpura, and increased skin pigmentation. It is a benign and chronic condition, although idiopathic in origin, the diagnosis is not a dilemma since it is mainly made by inspections and identification of classic morphology of the lesions. The biopsy is required to rule out mycosis fungoides. This activity highlights the role of the interprofessional team in the evaluation and treatment of Schamberg disease.

Objectives:

• Describes the etiology of Schamberg disease.
• Outline the typical morphology of the lesions in Schamberg disease.
• Identify the available treatment options for Schamberg disease.

Introduction

Schamberg disease represents the most common type of pigmented purpuric dermatoses (PPDs), a chronic, benign, cutaneous eruptions characterized by petechiae, purpura, and increased skin pigmentation (brown, red, or yellow patchy). The PPDs are grouped into five clinical entities: Schamberg's purpura, Majocchi purpura, lichen aureus, Gougerot-Blum purpura and, eczematoid-like purpura of Doucas and Kapetanakis.[1]

Schamber disease (SD) has also been called: progressive pigmentary dermatosis of Schamberg, purpura pigmentosa progressive and, Schamberg's purpura.[2] It is commonly seen in males and mainly affects the tibial regions, and could involve thighs, buttocks, trunk, or upper extremities.[3]

Etiology

The exact cause of Schamberg disease is not known. It is caused by extravasation of blood vessels particularly capillaries which allow red blood cells to get deposited into the skin which then releases their iron from hemoglobin. This iron causes a rust color accounting for the orange or brown tint of the rash.[4]

The exact cause of capillary inflammation is unknown and can be multifactorial. Potential contributors in the etiology can be:

1. Gravitational dependency[5]
2. Alcohol intake[6]
3. Drugs such as acetaminophen, aspirin, adalin, amlodipine, carbromal, chlordiazepoxide, glipizide, glybuzole, hydralazine, meprobamate, nitroglycerin, persantin, reserpine, thiamine, interferon-alfa, injection medroxyprogesterone acetate, topical fluorouracil, and sildenafil[7][8][9][10][11]
4. Genetic causes, as cases are seen in family members[12]
5. Hepatitis B antigenemia[12]
6. Dysfunctional immune system[13]
7. Idiopathic[5]

Epidemiology

PPDs include a spectrum of vascular diseases with an incidence of 0.18% of all skin diseases reported by Sharma and Gupta.[14] SD is the most common of the PPDs. It occurs in all races and ages ranging from 8 to 66 years (mean age 34 years), although a 19 month-old child has been reported.[1][14] It has a male preponderance, having M to F ratio between 5 and 3.8 to 1.[14] SD occurs more frequently in men, while purpura annularis telangiectodes of Majocchi occurs more frequently in females. Lichen aureus and Majocchi diseases occur commonly in children or young adults, while dermatosis of Gougerot and Blum affects middle-aged and older men.[1][4][14]

Pathophysiology

The main pathophysiological mechanism is the extravasation of red blood cells and the deposition of hemosiderin in macrophages.[1] There are indicators that exhibit the role of the cell-mediated immunity in the pathology, with a T-cell lymphocytic infiltrate perivascularly.[4] It has been suggested that medications act as haptens inducing the formation of antibody-antigen complexes.[15]

Reactive oxygen species generate inflammation, edema, and damage in the structure and function of the endothelial barrier, causing increased capillary permeability.[16] Various aggravating factors include hypertension, diabetes mellitus, venous stasis, strenuous exercise, gravitational dependency, capillary fragility, infections, and chemical ingestion has been related.[1]

Histopathology

Histopathology shows perivascular T-cell lymphocytic infiltrate around superficial small blood vessels composed of CD3+, CD4+, CD8+, CD1a+, CD36+, dendritic cells, cellular adhesion molecules (ICAM-1, ELAM-1), LFA-1; this infiltrate consequently will lead to endothelial cell swelling and narrowing of the lumen.[4][17]

Extravasation of red blood cells with marked hemosiderin deposition in macrophage is present in the superficial dermis, which can be seen by an iron stain.[4]

History and Physical

Schamberg disease is usually asymptomatic but can occasionally be itchy or painful. Many times, lesions resolve spontaneously. It is a chronic disease with different stages at the same time, while some are appearing older lesions will fade.[3]

Lesions are characterized by irregular localized well-circumscribed red, orange to brown or yellow non-bleachable patches pinhead-sized cayenne pepper spots of varying shapes and size in the form of multiple papules and macules beginning from the lower legs which gradually spreads in an ascending pattern to the rest of the body. The most common site affected is the bilateral lower extremities, thighs and buttocks are also frequently involved. Less commonly, it involves upper extremity or can be generalized.[4][18]

Evaluation

The diagnosis is usually made by clinical inspection and identification of the classic morphology of the lesions. Although a biopsy is not mandatory, it is useful to rule out differential diagnoses.

Capillary fragility can be assessed by the Hess’s or Rumpel-Leede test, also called a tourniquet test. For this test, the pressure is applied to the forearm with a blood pressure cuff inflated between systolic and diastolic blood pressure for 5 to 10 minutes. After removing the cuff, fifteen or more petechiae in a 5 cm diameter area indicates capillary fragility. It occurs due to poor platelet function.[19]

Dermoscopy is a diagnostic tool to examine the skin using a special magnifying lens. In SD it shows coppery-red pigmentation as the most common finding in 97%, followed by red globules in 75%, then red dots (69%), brown dots (53%), reticular network (34%), red patch (34%), brown globules (26%), and linear vessels (22%).[20]

No laboratory abnormalities are associated with SD although a complete blood count and peripheral blood smear are necessary to exclude infection and thrombocytopenia, coagulation screening helps to exclude other possible causes of purpura; other recommended tests are bleeding time, platelet aggregation function, ANA, RF, anti-HBsAg antibody and anti-HCV antibody.[20]

Skin biopsy: Histopathology shows perivascular T-cell lymphocytic infiltrate around superficial small blood vessels, extravasation of red blood cells with marked hemosiderin deposition in macrophage in the superficial dermis.[4]

Treatment / Management

Schamberg disease is still considered idiopathic. Without an established therapy, treatment is sometimes ineffective, and recurrences are not uncommon. It is not life-threatening or causes any major health concern. Reassurance about the chronic and benign nature of the disease is required, and residual pigmentation could last for years.[4]

First-line interventions are nonpharmacologic interventions and topical steroids. Various non-drug strategies are aimed at eliminating or reducing potential contributing factors such as discontinuing or changing the offending medication, avoiding food preservatives and artificial coloring agents, and wearing support stockings to counteract abnormal vein function.

The itching will improve with moisturizing, oral antihistamines, and topical steroids, such as cortisone or betamethasone, may be used. Topical steroids decrease inflammation by suppressing the migration of polymorphonuclear leukocytes and reversing capillary permeability.[4] The use of anti-inflammatory drugs is used to treat skin diseases by immune mediation.[21]

Second-line intervention: Pentoxifylline, a methylxanthine derivative, acts by various mechanisms.

1. Potent rheological and anti-inflammatories properties.[22]
2. Immunomodulatory action by modifying cytokine profile and anti-fibroblastic action.[23]
3. A decrease in expression of ICAM-I on endothelial cells of blood vessels that leads to decreased exudation of inflammatory cells from capillaries into the surrounding perivascular tissue.[23][24]
4. Inhibits synthesis and release of TNF-a, which also reduces the extravasation of blood from the capillaries.[23]

Different clinical trials reported a clinical improvement from the 2-3 weeks until six months, with doses ranging from 100-400 mg three times a day.[22][23]

Phototherapy had shown to be effective in a few case reports. Most of these were resistant to other therapies. Narrowband ultraviolet B therapy-induced immunomodulation by suppression of the interleukin-2 production and altering the T cells activity. It was used in two children and one adult two-three times a week for 10-20 treatments with improvement and without recurrence during the follow-up.[25][26] Although it was effective in an adult, the treatment should be continued for a long period.[27]

PUVA phototherapy diminished the CD4+ and CD1a+ cells and the adhesion molecule receptor and had proved to be effective in eight patients.[28][29][30] Intense pulse laser (IPL) acts through the absorption by the hemoglobin in the vessels generating thermal damage. The Advanced Fluorescence Technology, a new generation of IPL, selectively targets hemosiderin within macrophages and hemoglobin within extravasated erythrocytes shown to be effective in 5 patients.[31]

Multiple other therapies have been utilized for SD, although only a few of them have been effective.

Ascorbic acid and bioflavonoids have additive antioxidative properties that wield an angio-protective and anti-inflammatory effect. It also decreases the permeability of endothelial cells and reduces capillary permeability and fragility by increasing their resistance. Three patients were treated with 500 mg bid and 50 mg bid, respectively, with clinical improvement at four weeks.[16]

Colchicine 0.5 g bid has been used with the improvement from the first week to complete clearance by the four months.[32][33] Aminaphtone helps reduce capillary fragility, and red blood cell leakage reported improvement with 75mg bid for one month without recurrence for one year after suspended.[34] Griseofulvin could have an immunomodulatory activity improving the SD at a dose of 500-750 mg since the first week.[35] Variable results are found with other drugs, also like oral cyclosporin, calcineurin-inhibitors, methotrexate.[24][4][36]

Differential Diagnosis

Differential diagnosis should be made with other cutaneous lesions that may present with petechiae, purpura, or localized hyperpigmentation related to hemosiderin deposition such as other DPPs.

Purpura annularis telangiectodes (Majocci disease), is characterized by annular, purpuric lesions and erythematous punctate lesions, and central clearing with slight atrophy.

Touraine, a variant of Majocci’s Disease, exhibits a purpura telangiectatic arciform, with fewer lesions, larger, and irregularly arciform.[4]

Pigmented purpuric dermatosis of Gougerot and Blum is characterized by red-brown lichenoid papules that tend to fuse in plaques in older men.[4][3]

Eczematoid like purpura of Doucas and Kapetanakis is usually bilateral, intensely itchy, and characteristically has eczematous features. Mild lichenification could be present and has a fluctuation course with spontaneous improvement occasionally.[4][37]

Stasis dermatitis exhibits eczematous patches that progress to red-brown or brownish colored irregular patches, associated varicosities, and leg edema, although both entities could coexist.[38]

Leukocytoclastic vasculitis hemorrhagic bullae and brown pigmentation consistent with hemosiderin deposits, the palpable nature of the lesions, and the histopathology report differentiate it from SD.[39]

Nonaccidental injury exhibit a purpuric patch that evolves and resolves in a few weeks.

Mycosis fungoides can be challenging to distinguish from SD, histopathology detection in the epidermis of large groups of lymphocytes, or many lymphocytes in the spinous layer favor mycosis fungoides.[40]

Scurvy purpuric lesions could be confused, other features in scurvy such as perifollicular purpura, coiled hairs, bleeding gums, and dietary history of reduced vitamin C intake supports scurvy.[41]

Drug hypersensitivity reactions due to rituximab, carbamazepine, meprobamate, bufexamac, chlordiazepoxide, furosemide, nitroglycerin, vitamin B-1, or medroxyprogesterone acetate.[4]

Prognosis

The course of the condition is typically chronic, with numerous exacerbations and remissions. Lesions could persist or extend with time and spontaneous resolution also may occur in a period ranging from months to years. Ratnam et al reported in a series of cases in which 62% of the patients cleared entirely while 38% remained stable or experienced worsening of their symptoms.[4][5]

Complications

In general, SD is a benign condition, although it can cause worsening and recurrent chronic skin lesions, resistant to treatment.

There are infrequent reports of patients with SD that developed mycosis fungoides presented as SD. Clinical and histopathological properties shared some similarities. Although it is rare to develop mycosis fungoides after an initial diagnosis of SD this could be suspected when has a long-lasting course (>1 year), and follow-up could be made every year.[42]

Emotional stress and psychological trauma can come due to the longstanding pigmentation in the skin leading to depression and anxiety in some patients.

Deterrence and Patient Education

Leg elevation is advised.

Venous stasis should be controlled with a compression bandage.

Prolonged leg dependency should be avoided.

Patients are advised to avoid precipitating factors like any food or food additives with preservatives and artificial colors.

Enhancing Healthcare Team Outcomes

Schamberg disease represents one of the most common types of pigmented purpuric dermatoses diagnosis is usually made by clinical inspection, although a biopsy is always useful for differential diagnosis, it is not mandatory. The exact cause of Shamberg´s disease is not known. T-cell mediated immunity plays an important role in the pathology; there is also a multifactorial component including gravitational dependency, alcohol intake, drugs, a genetic component, hepatitis B antigenemia, and dysfunctional immune system. This type of purpuric dermatoses affects all races and usually affects older adults with a male preponderance.

While Schamberg disease usually does not represent a diagnostic dilemma, treatment does. Since there is not an established therapy, the options are wide, such as topical steroids, phototherapy, pentoxifylline, colchicine, oral cyclosporine, griseofulvin, ascorbic acid, and other infrequent treatments. Among them, phototherapy has been considered in patients who fail topical therapy, even though larger studies are required to confirm phototherapy as a promising therapy. Although the treatment variety is wide, the expert opinion from the specialist is useful to select the appropriate therapy.

Differential diagnosis is crucial and is mainly depends upon thorough clinical inspection and identification of classic morphology. The histopathology plays a vital role in differentiating from mycosis fungoides. Although this is a benign disease, numerous exacerbations and spontaneous resolution can be discouraging in some patients. The residual pigmentation could induce depression and anxiety in patients. Therefore, psychological support is crucial in these circumstances.

The outcomes in Schamberg disease is usually good. There could be relapses, and the treatments could be extended even for years, therefore keeping the patient motivated is crucial to complete the treatment.