Pigmented purpuric dermatoses (capillaritis)

INTRODUCTION — The pigmented purpuric dermatoses (PPDs), also known as capillaritis, purpura simplex, and inflammatory purpura without vasculitis, are a group of chronic, benign, cutaneous eruptions characterized by the presence of petechiae, purpura, and increased skin pigmentation. PPDs most commonly occur on the lower extremities and may be asymptomatic or pruritic.

Familiarity with the clinical and pathologic findings of PPDs is useful for distinguishing them from cutaneous vasculitis and other disorders that may present with similar clinical features. The classic pathologic findings of PPDs include a perivascular mononuclear cell inflammatory infiltrate, erythrocyte extravasation, and hemosiderin deposition.

The diagnosis and treatment of PPDs will be reviewed here. Cutaneous vasculitis is discussed separately. (See "Evaluation of adults with cutaneous lesions of vasculitis" and "Management of adults with idiopathic cutaneous small vessel vasculitis".)

EPIDEMIOLOGY — Data are limited on the epidemiology of pigmented purpuric dermatoses (PPDs). Overall, these disorders are considered to be uncommon [1]. The major subtypes of PPD include:

●Schamberg disease (the most common form of PPD [2,3], also known as progressive pigmentary purpura)

●Purpura annularis telangiectodes (also known as Majocchi disease)

●Pigmented purpuric lichenoid dermatitis of Gougerot and Blum

●Lichen aureus

●Eczematid-like purpura of Doucas and Kapetanakis

Rare, additional subtypes of PPD include itching purpura, unilateral linear capillaritis, and granulomatous pigmented purpura. Some authors have considered eczematid-like purpura of Doucas and Kapetanakis and itching purpura as a single entity [4,5].

Although PPD can develop at any age, age predilections have been observed in some subtypes [2,4,6-8]:

●Schamberg disease – Middle-aged adults

●Purpura annularis telangiectodes – Adolescents and young adults

●Pigmented purpuric lichenoid dermatitis of Gougerot and Blum – Adults

●Lichen aureus – Young adults

●Eczematid-like purpura of Doucas and Kapetanakis – Middle-aged adults

●Itching purpura – Middle-aged adults

●Unilateral linear capillaritis – Young adults

●Granulomatous pigmented purpura – Adults

Children are not excluded from the development of PPDs [2,9]. Schamberg disease is the most common cause of petechiae in children [2,3,9], and has been documented in a child as young as one year [10]. In addition, there are multiple published reports of lichen aureus in children [11-19].

Data are insufficient to confirm whether sex predilections exist among PPDs, and two of the largest series have found conflicting results regarding whether Schamberg disease is more common in males or females [5,7].

ETIOLOGY AND PATHOGENESIS — Multiple factors have been proposed as potential contributors to the development of pigmented purpuric dermatoses (PPDs), though none have been definitively proven. These include [2,4,20]:

●Venous insufficiency [21]

●Gravitational dependency

●Aerobic exercise

●Localized infection [22]

●Alcohol [23]

●Chemical ingestion

●Contact allergens (table 1) [24-34]

●Drugs (table 2) [35-47]

●Systemic diseases

●Flu vaccine [48]

●Coronavirus disease 2019 (COVID-19) vaccination [49,50]

In PPDs linked to drug exposure, times of onset ranging from one week to years after the start of drug treatment have been reported [35-45].

Associations between PPD and multiple systemic diseases have been proposed [5]. Examples of the most commonly cited associations include hyperlipidemia (granulomatous PPD) [20,51-53] and viral hepatitis [54-57]. However, the relationship between PPD and these disorders is uncertain. A case-control study of 60 patients with PPD and 230 controls did not find significant differences in the prevalence of hepatitis B or C among the patients with PPD [58]. PPDs are not manifestations of platelet abnormalities or bleeding disorders.

Some authors have considered PPD a form of a cutaneous T cell lymphoid dyscrasia based upon infrequent reports of PPD progressing to mycosis fungoides, similarities in the clinical and histologic features of PPD and mycosis fungoides, and the frequent detection of T cell monoclonality in lesions of PPD [59]. Further study is necessary to clarify the relationship between mycosis fungoides and PPD. (See 'Relationship to mycosis fungoides' below.)

There is a paucity of data on the pathogenic mechanisms that lead to the clinical findings of PPD, and thus, the mechanisms through which PPD develops are poorly understood. Three theories that have arisen based upon interpretation of the histologic and immunohistochemical findings in PPD are reviewed below:

●Vascular abnormalities – Extravasation of erythrocytes in the dermis is a characteristic pathologic feature of PPD. A state of capillary fragility has been postulated to contribute to capillary rupture and erythrocyte extravasation consistent with that observed in PPD [2]. Increased pressure in the cutaneous microvasculature secondary to venous stasis has also been proposed as a contributing factor [60].

●Cell-mediated immunity – A mononuclear inflammatory cell infiltrate of varying extent is typically found in pathology specimens of PPD, and it is conceivable that a perivascular cell-mediated immune response could contribute to capillary damage and erythrocyte leakage [61]. The nature of the inflammatory infiltrate in Schamberg disease was investigated in a study of tissue specimens from five adults with the condition [62]. The infiltrate was primarily composed of CD4⁺ lymphocytes and CD1a⁺ dendritic cells. In addition, upregulation of adhesion molecules that could facilitate inflammatory cell trafficking was detected on infiltrating lymphocytes (LFA-1 and ICAM-1) and endothelial cells (ICAM-1 and ELAM-1).

●Humoral immunity – A potential role for immune complex disease in PPD has been suggested based upon reports documenting direct immunofluorescence findings of vascular deposits of C3, C1q, IgM, or IgA within lesional skin [5,63,64].

As a consequence of limited research, the role of each of these factors in the development of PPD remains uncertain. Additional studies are necessary to elucidate the pathophysiology of this disorder.

CLINICAL FEATURES — The key clinical features of all pigmented purpuric dermatoses (PPDs) are petechiae or purpura, which reflect erythrocyte extravasation, and yellow to brown pigmented patches, which result from hemosiderin deposition within the dermis. The most common sites for PPDs are the lower extremities, although lesions also may develop in other areas. Infrequently, PPDs present as generalized eruptions. The palms, soles, genitalia, and mucosa are typically spared.

The clinical findings that distinguish the PPD subtypes are reviewed below.

Schamberg disease (progressive pigmentary purpura) — First described by Jay Frank Schamberg in 1901 [65], Schamberg disease presents with discrete, nonblanchable, red-brown purpuric patches that are usually a few millimeters to several millimeters in diameter, although some patches may reach several centimeters in breadth (picture 1A-C). Close inspection of the patches reveals nonpalpable pinpoint petechiae that were described by Schamberg as "pinpoint to pinhead sized reddish puncta, closely resembling grains of cayenne pepper" [65]. The most common site for involvement is the bilateral lower extremities (below the knees). The thighs and buttocks are also frequently involved. Less commonly, Schamberg disease presents with upper extremity or generalized involvement. Although Schamberg disease is usually asymptomatic, occasional patients experience mild pruritus.

The course of the condition is typically chronic, with numerous exacerbations and remissions. Spontaneous resolution also may occur [5,9,66-70]. In a retrospective series that included at least three years of follow-up data on each of the 45 patients with Schamberg disease, 62 percent cleared or improved and 38 percent remained stable or experienced worsening of symptoms [5].

Purpura annularis telangiectodes (Majocchi disease) — Initially described by Domenico Majocchi in 1896 [71], purpura annularis telangiectodes presents with nonblanchable, annular, 2 to 20 cm, symmetrical, purpuric, telangiectatic patches (picture 2A-B). Unilateral disease is reported in one patient [72]. Linear or arciform patches may also be present. Occasionally, atrophy is evident in the center of lesions [73].

As with Schamberg disease, the most common site for involvement is the lower extremities [74]. Extension to the upper extremities and trunk may occur.

The cutaneous lesions of purpura annularis telangiectodes usually are asymptomatic. Occasionally, mild pruritus is present [73,75]. The course is chronic and characterized by relapses and remissions [73]. Individual lesions typically last several months.

Pigmented purpuric lichenoid dermatitis of Gougerot and Blum — Patients with pigmented purpuric lichenoid dermatitis of Gougerot and Blum develop small polygonal or round lichenoid purpuric papules that coalesce to form red-brown to violaceous plaques that are one to several centimeters in diameter (picture 3) [76]. The appearance of the plaques may resemble Kaposi sarcoma [77]. Like other subtypes of PPD, this eruption usually is found on the lower extremities. Rarely, there is involvement of the upper extremities or trunk. The course of pigmented purpuric lichenoid dermatitis of Gougerot and Blum tends to be chronic, although spontaneous remission may occur [4].

Lichen aureus — Lichen aureus (originally termed "lichen purpuricus") presents with the acute onset of distinctive, rust-yellow or gold colored lichenoid papules or circumscribed patches and plaques (picture 4) [78]. The term "lichen aureus" emphasizes the classic gold-brown color of the eruption [79]. Of note, lichen aureus also may present with copper-orange or violaceous lesions.

Lichen aureus most frequently occurs unilaterally on the lower extremities; bilateral involvement is less common [11,15,80]. Other reported distributions include upper extremity and trunk involvement; segmental, dermatomal, and Blaschkoid arrangements; and involvement that follows the course of superficial or deep veins [80-85]. Aberrant locations and distributions may occur more commonly in children [11].

Lichen aureus typically is asymptomatic. Occasionally, patients experience intense pruritus.

Lichen aureus tends to persist for multiple years, and, in some cases, is slowly progressive [80,86]. In a retrospective study of 42 patients with lichen aureus (age of onset 3 to 70 years), lesions tended to persist during the follow-up period of 3 months to 19 years [80]. Complete resolution was reported for only two patients. In contrast, spontaneous resolution was observed more frequently in a series of eight children with lichen aureus; five experienced resolution within two to six years (mean 3.4 years), two had reduced but continued lesions beyond four to five years, and one had persistent lesions at three years [11].

Eczematid-like purpura of Doucas and Kapetanakis — Eczematid-like purpura of Doucas and Kapetanakis is distinguished from other forms of PPD by the concomitant presence of eczematous features. The eruption usually begins with the insidious onset of groups of nonblanchable pinpoint red macules that evolve to a darker red or yellow-brown color over a few weeks [6]. The eruption typically begins on the lower extremities and may spread to the upper extremities or trunk. The face, neck, palms, and soles typically are spared.

Erythema and mild scale develop within the involved areas, resulting in an appearance that mimics eczema (picture 5A-B). Pruritus is common. Mild lichenification secondary to rubbing and scratching may be present.

Eczematid-like purpura of Doucas and Kapetanakis follows a fluctuating course. The eruption usually spontaneously resolves within several months to two years [6].

Rare variants — Rarely reported variants of PPD include itching purpura, unilateral linear capillaritis, and granulomatous pigmented purpura:

●Itching purpura – Itching purpura (also known as disseminated pruriginous angiodermatitis) is characterized by the acute onset of orange-brown to purpuric macules on the lower extremities. The lesions often subsequently become generalized. Unlike most other types of PPD, the condition is associated with severe pruritus [87,88]. Itching purpura has a chronic course, though spontaneous remissions occur.

●Unilateral linear capillaritis – Unilateral linear capillaritis (also known as segmental pigmented purpura and quadrantic capillaropathy) describes the development of pigmented purpura in a linear, dermatomal, or segmental distribution (picture 6) [89-93]. The condition primarily has been reported in young adults and children on the lower extremity or upper extremity [89,90]. The prognosis appears to be good; in a series of four males with lower extremity lesions, significant regression of skin lesions occurred within three years in all patients [89].

●Granulomatous pigmented purpura – Approximately 20 cases of granulomatous pigmented purpura have been reported in the literature [20,51-53,94-100]. The condition usually presents with multiple erythematous to brown purpuric macules or papules and is distinguished from other types of PPD by the detection of a granulomatous infiltrate on histopathology (picture 7A-B). The most common sites of involvement are the dorsum of the feet and the legs. Less frequently, wrists and hands have been affected. A blaschkoid distribution has also been reported [101].

Many of the reported cases have occurred in patients who also had hyperlipidemia, prompting some authors to question whether a relationship between these disorders exists [51-53,98,99]. The cutaneous lesions may persist for years [52].

HISTOPATHOLOGY — The pigmented purpuric dermatoses (PPDs) subtypes share several histopathologic features, including [5,59,102]:

●A superficial, perivascular, inflammatory infiltrate (primarily CD4⁺ lymphocytes with occasional dendritic cells and macrophages)

●Endothelial cell proliferation and edema; narrowing of vessel lumens

●Extravasation of erythrocytes in the papillary dermis

●Variable degree of hemosiderin deposition in macrophages in the dermis (particularly in mature lesions)

●Lymphocyte exocytosis

●Variable mild vacuolar degeneration at the basal layer

Histochemical stains that stain iron, such as the Perls or Fontana Masson stain, are useful for highlighting hemosiderin deposition in the superficial dermis. Of note, features of leukocytoclastic vasculitis (eg, leukocytoclasia and fibrinoid necrosis of vessel walls) are absent. (See "Evaluation of adults with cutaneous lesions of vasculitis", section on 'Diagnostic criteria'.)

Depending on the clinical subtype of PPD, additional histopathologic features may be present:

●Schamberg disease – Variable degree of epidermal spongiosis [4]

●Pigmented purpuric lichenoid dermatitis of Gougerot and Blum – Band-like (lichenoid), lymphocytic infiltrate in the upper dermis with or without epidermal spongiosis [103]

●Lichen aureus – Dense, lichenoid, lymphocytic infiltrate in the upper dermis and at the dermal-epidermal junction; variable degree of lymphocyte exocytosis; with or without a Grenz zone (an area of uninvolved connective tissue that separates the dermal infiltrate from the epidermis) [80]

●Eczematoid purpura of Doucas and Kapetanakis – Epidermal spongiosis [6]

●Itching purpura – Epidermal spongiosis, marked inflammatory response that includes neutrophils [102]

●Granulomatous pigmented purpura – Mononuclear cell infiltrate accompanied by a granulomatous infiltrate in the papillary dermis [94]

LABORATORY FINDINGS — No laboratory abnormalities are associated with pigmented purpuric dermatoses (PPDs). Laboratory tests that assess for platelet abnormalities, coagulopathies, or acute phase reactants are expected to be normal.

DIAGNOSIS — The presence of discrete or circumscribed, nonpalpable, purpuric macules and patches (particularly on the lower extremity) with petechiae and yellow-brown pigmentation suggests the possibility of pigmented purpuric dermatoses (PPDs), particularly Schamberg disease, the classic form of PPD. Palpable lesions exhibiting similar features suggest variants of PPD that often present with papules or plaques, such as lichen aureus, eczematid-like purpura of Doucas and Kapetanakis, and granulomatous pigmented purpura. The diagnosis is usually made through clinical inspection and the recognition of classic morphologic features.

Dermoscopy may be a useful adjunct to clinical inspection with the naked eye. A review of 32 patients with PPD suggests that dermoscopic findings in lesions of pigmented purpura may include coppery-red pigmentation in the background; a brown network; linear vessels; round to oval, red dots, globules, and patches; brown globules and dots; linear brown line; and follicular openings [104]. Dermoscopy may also help distinguish purpuric mycosis fungoides (PMF) from PPD; in a study of 28 patients with PMF and 13 patients with PPD, fine, short, linear vessels and spermatozoa-like structures were more common in PMF lesions [105].

A skin biopsy is useful when the diagnosis remains uncertain following clinical examination. Biopsies may help to distinguish PPD from disorders in the differential diagnosis, such as cutaneous vasculitis. (See 'Differential diagnosis' below.)

DIFFERENTIAL DIAGNOSIS — The differential diagnosis of pigmented purpuric dermatoses (PPDs) consists of other cutaneous lesions that may present with petechiae, purpura, eczematous features, or localized hyperpigmentation related to hemosiderin deposition. A careful clinical assessment and biopsy (when needed) can aid in distinguishing PPD from other disorders. Stasis dermatitis, cutaneous vasculitis, traumatic purpura, and mycosis fungoides are among the disorders most likely to be confused with PPD:

●Stasis dermatitis – Stasis dermatitis shares both clinical and pathologic features with PPD. Stasis dermatitis usually presents on the lower extremities with insidious onset of eczematous patches that progress to red-brown or brawny colored irregular patches (picture 8A-B). Associated varicosities and leg edema are often present. The medial ankle is the most common site of initial involvement. Like PPD, the pathology findings of stasis dermatitis include epidermal spongiosis, a perivascular lymphocytic infiltrate, dilated dermal capillaries with intimal thickening, and hemosiderin within dermal macrophages. Clinicians should be aware that stasis dermatitis and PPD may coexist. (See "Stasis dermatitis".)

●Cutaneous vasculitis – Cutaneous leukocytoclastic vasculitis presents with the acute onset of palpable purpura, often primarily involving the lower extremities and other dependent areas of the body. Hemorrhagic bullae and brown pigmentation consistent with hemosiderin deposition in the skin also may be present (picture 9A-D). The palpable nature of this disorder is useful for distinguishing it from Schamberg disease and purpura annularis telangiectodes, which present with nonpalpable petechiae and/or purpura. A skin biopsy can distinguish vasculitis from PPD; the vessel destruction, leukocytoclasia, and fibrinoid necrosis characteristic of vasculitis are not found in PPD. (See "Evaluation of adults with cutaneous lesions of vasculitis".)

●Traumatic purpura – Injury to the skin may result in the development of purpuric patches. Traumatic purpura are much less persistent than PPDs, typically evolving and resolving over the course of a few weeks.

●Mycosis fungoides – PPD is sometimes difficult to distinguish from mycosis fungoides. Infrequently, purpura is an initial manifestation of mycosis fungoides, and the two disorders can have overlapping histologic features (eg, lichenoid infiltrate, lymphocytes invading the epidermis). In cases in which the clinical features suggest PPD, but pathologic examination raises the question of mycosis fungoides, distinguishing between the conditions can be challenging. The detection of large intraepidermal groups of lymphocytes or many lymphocytes in the spinous layer of the epidermis favor a diagnosis of mycosis fungoides [106]. (See 'Relationship to mycosis fungoides' below and "Clinical manifestations, pathologic features, and diagnosis of mycosis fungoides".)

Additional disorders that may enter the differential diagnosis of a patient with specific forms of PPD include scurvy, dermatitis, and Kaposi sarcoma:

●Scurvy – The purpuric lesions of scurvy may be confused with the scattered petechiae and purpura of Schamberg disease (picture 10A-B). The detection of perifollicular purpura, corkscrew-shaped hairs, bleeding gums, and a dietary history of reduced vitamin C intake support a diagnosis of scurvy. (See "Overview of water-soluble vitamins", section on 'Deficiency'.)

●Eczematous dermatitis – Additional disorders that should be considered in the differential diagnosis of eczematid-like purpura of Doucas and Kapetanakis include atopic dermatitis, nummular eczema, and allergic contact dermatitis (picture 11A-D). These disorders can be clinically distinguished from this subtype of PPD by the absence of petechiae, purpura, and the yellow-brown pigmentation characteristic of PPDs. In addition, the pathologic findings of atopic dermatitis and allergic contact dermatitis do not include erythrocyte extravasation and hemosiderin deposition. (See "Atopic dermatitis (eczema): Pathogenesis, clinical manifestations, and diagnosis", section on 'Clinical manifestations'.)

●Kaposi sarcoma – Kaposi sarcoma may mimic the presentation of pigmented purpuric lichenoid dermatitis of Gougerot and Blum. Cutaneous lesions of Kaposi sarcoma appear as violaceous macules, papules, plaques, or nodules, most commonly on the lower extremities, head, neck, and oral mucosa (picture 12). The last three sites are typically spared in PPD. Kaposi sarcoma is easily distinguished from PPD through pathology findings of vascular proliferation, dermal spindle cells, and vascular slits. (See "Classic Kaposi sarcoma: Clinical features, staging, diagnosis, and treatment" and "AIDS-related Kaposi sarcoma: Clinical manifestations and diagnosis".)

TREATMENT — Pigmented purpuric dermatoses (PPDs) are benign conditions that are often asymptomatic. Thus, treatment is not always necessary and reassurance is an acceptable course of management for most patients. Treatment is generally considered for patients with associated symptoms and for patients who are distressed by the cosmetic appearance of the skin lesions.

Because most data on the efficacy of treatments are derived from case reports and small case series and spontaneous resolution of PPD is possible, the best approach to treatment remains uncertain. In our experience, the response to treatment is unpredictable and often poor. Given the benign nature of PPDs, the risk-benefit ratio of treatment always should be considered.

When patients desire treatment, we typically begin with measures to reduce exacerbating factors or topical corticosteroids due to the relative safety of these interventions. We reserve other interventions for patients with extensive involvement or topical corticosteroid-refractory lesions who also have a strong desire for additional treatment.

First-line interventions — Our first-line therapies for PPDs are nonpharmacologic interventions and topical corticosteroids.

Nonpharmacologic interventions — Non-drug interventions for PPD are aimed at eliminating or reducing potential contributing factors. In patients in whom the development of a PPD appears to correlate with exposure to a medication or contact allergen, discontinuation of exposure to the potential inciting agent should be implemented whenever feasible. (See 'Etiology and pathogenesis' above.)

Due to the theory that increased vascular pressure may contribute to capillary leakage in PPDs, many clinicians, including ourselves, often have patients with PPDs on the lower extremities wear supportive stockings, particularly if concomitant signs of venous stasis are present. However, the efficacy of this measure for accelerating resolution of the PPD is unproven.

Topical corticosteroids — Topical corticosteroids have been used for PPD based upon the histologic evidence that PPD is an inflammatory process. Although some case reports and case series have documented improvement in PPD during topical corticosteroid therapy, the response to treatment is inconsistent [4,5,9,13,51,107-109]. Randomized controlled trials of topical corticosteroid therapy for PPD have not been performed.

When treating with topical corticosteroids, we typically prescribe application of a medium potency or high potency topical corticosteroid once to twice daily to affected areas for four to six weeks (table 3) [1]. If no improvement is detected within this period, we discontinue topical corticosteroid treatment.

Cutaneous atrophy is a potential adverse effect of topical corticosteroid treatment. The adverse effects of this treatment are reviewed in greater detail separately. (See "Topical corticosteroids: Use and adverse effects", section on 'Adverse effects'.)

Second-line intervention — Phototherapy is a well-tolerated skin-directed treatment that appears to be of value for some patients with PPD. We consider phototherapy for patients who fail topical corticosteroid therapy or for patients for whom topical therapy is impractical due to extensive involvement. Data on the long-term benefit of phototherapy after treatment cessation are limited.

Phototherapy — Case reports and small case series have documented improvement in PPDs with ultraviolet B (UVB) or psoralen plus ultraviolet A (PUVA) phototherapy. Multiple treatment sessions are required. The repeated visits required for phototherapy are a deterrent to treatment for some patients (see "UVB phototherapy (broadband and narrowband)" and "Psoralen plus ultraviolet A (PUVA) photochemotherapy"):

●Narrowband ultraviolet B – In a prospective uncontrolled study of five patients with Schamberg disease and one patient with purpura annularis telangiectodes, treatment with narrowband ultraviolet B (NBUVB) three times per week led to a good response (more than 75 percent reduction in petechiae and pigmentation) in all patients within 24 to 28 treatment sessions [110]. Subsequently, maintenance treatments were given twice per week for three weeks followed by once per week for three weeks. The two patients who relapsed during the one-year follow-up period improved with additional sessions of NBUVB treatment.

Case reports and case series describe other patients with PPD [111-114] (including children [9,114,115]) who seemed to respond well to NBUVB phototherapy. For example, patients with pigmented purpuric lichenoid dermatitis of Gougerot and Blum have achieved improvement or lesion clearance during NBUVB phototherapy [9,116].

●Psoralen plus ultraviolet A – Psoralen plus ultraviolet A (PUVA) phototherapy involves the administration of a psoralen prior to irradiation with ultraviolet A (UVA) light. In a series of 11 adults treated with PUVA for PPD (five with Schamberg disease, five with pigmented lichenoid dermatitis of Gougerot and Blum, and one with eczematid-like purpura of Doucas and Kapetanakis), all patients achieved lesion clearance [117]. Moreover, dramatic reductions in CD4⁺ and CD1a cells and adhesion molecule expression were detected following PUVA therapy. A separate series of seven adults with pigmented purpuric lichenoid dermatitis of Gougerot and Blum also seemed to demonstrate benefit of PUVA; all patients achieved clearance of skin lesions within 7 to 20 PUVA treatments [63]. Two patients who relapsed one month after treatment cessation responded to a second course of treatment.

Improvement in PPD during PUVA also has been reported in case reports of patients with Schamberg disease [118], lichen aureus [119], and unilateral linear capillaritis [90].

Potential adverse effects of phototherapy include sunburns, blistering, pruritus, and skin aging. Increased risk for skin cancer has been reported in psoriasis patients who have received high numbers of PUVA treatments. The side effects of phototherapy are reviewed in greater detail separately. (See "UVB phototherapy (broadband and narrowband)", section on 'Short- and long-term adverse effects' and "Psoralen plus ultraviolet A (PUVA) photochemotherapy", section on 'Adverse effects'.)

Other interventions — Multiple other therapies have been utilized for PPD. Only pentoxifylline has been evaluated in a randomized trial.

Pentoxifylline — Pentoxifylline may have beneficial effects on Schamberg disease. Pentoxifylline is a drug that inhibits adhesion of leukocytes to endothelial cells and can stimulate vascular endothelium to release PGI₂, which inhibits platelet adhesion and aggregation [85]. Pentoxifylline is also used for the management of lower extremity chronic venous disease.

A single-blind randomized trial of 112 adults with moderate to severe Schamberg disease compared eight weeks of treatment with pentoxifylline (400 mg three times per day) to topical betamethasone dipropionate 0.05% cream (applied twice daily for eight weeks) [120]. Whereas 34 patients in the pentoxifylline group (61 percent) had a statistically significant reduction in a disease severity score after two months, this occurred in only 12 of 56 patients in the corticosteroid group (21 percent). By four months after treatment cessation, statistically significant reductions in the severity score remained in 14 patients in the pentoxifylline group and 8 patients in the corticosteroid group. Whether cosmetically significant responses were obtained is unclear.

Case reports and small case series of pentoxifylline for Schamberg disease have documented both marked clinical improvement in patients with 300 mg per day or 400 mg three times daily [121,122] and treatment failure in patients treated with 300 to 600 mg per day [123,124]. Further studies are necessary to confirm the clinical value of the drug for PPD. Partial improvement following combination therapy with pentoxifylline and prostacyclin (PGI₂) was reported in a patient with segmental lichen aureus [85].

Treatment with pentoxifylline is generally well tolerated. Gastrointestinal symptoms (eg, nausea, vomiting) are the most common adverse effects.

Other — Other therapies that have been reported to be beneficial for PPD in small numbers of patients include griseofulvin [125], calcium dobesilate (500 mg twice daily) [126], colchicine (0.5 mg twice daily) [127,128], tacrolimus ointment [129], pimecrolimus cream [73], photodynamic therapy [130], pulse dye laser [131,132], and alexandrite laser [133]. Immunosuppressants such as systemic glucocorticoids [111], cyclosporine [134], and methotrexate [73] have been used successfully, but generally are not indicated given the potential adverse effects of these agents and the minimal data to support their efficacy.

An oral bioflavonoid (rutoside) 50 mg twice daily and ascorbic acid (500 mg twice daily) has been reported to improve PPD [6,135,136]. In a two center retrospective case series of 35 patients with Schamberg disease receiving rutoside 50 mg twice daily and 1000 mg ascorbic acid once daily with a mean treatment duration of 8.2 months, 71 percent experienced complete clearance and 20 percent experienced improvement of greater than 50 percent. Nine participants (25 percent) relapsed after discontinuation. Seven of these patients responded to reinitiation of rutoside and ascorbic acid. Those with shorter disease duration had better responses, shorter time to response, and lower risk of recurrence [136].

PROGNOSIS AND FOLLOW-UP — In general, pigmented purpuric dermatoses (PPDs) are benign, chronic conditions. Eruptions persist, wax and wane, or slowly progress, and may clear spontaneously over a period of months to years. The clinical courses of specific forms of PPD are reviewed above. (See 'Clinical features' above.)

Relationship to mycosis fungoides — Infrequent reports of patients in whom a diagnosis of PPD preceded a diagnosis of mycosis fungoides or in whom mycosis fungoides presented with clinical features of PPD, as well as studies that have found shared clinical and histologic features between the two disorders, have led to uncertainty about the relationship between mycosis fungoides and PPD [59,106,137-144]. As an example, in a study of 56 biopsy specimens from patients with PPD, 29 (52 percent) exhibited pathologic patterns that have been associated with mycosis fungoides [106].

Similar to mycosis fungoides, monoclonal expansion of T cells is frequently detected in patients with PPD [15,59,106,145]. The authors of one study found that patients diagnosed with PPD who had monoclonal expansion were more likely to exhibit clinical and pathologic features similar to those of mycosis fungoides and proposed that PPD may represent a form of cutaneous T cell lymphoid dyscrasia [59]. In another study, 8 of 12 PPD biopsy specimens that had lichenoid histologic patterns exhibited monoclonality [106].

The clinical significance of monoclonal expansion in PPD is uncertain; clinical experience suggests that the development of mycosis fungoides after an initial diagnosis of PPD is rare. A review of 23 patients with lichen aureus found that although 8 of 16 patients who had T cell receptor-γ gene rearrangement performed had a monoclonal T cell population, after a mean follow-up of 102 months (range 11 to 382 months), none of the patients in the study developed mycosis fungoides [15].

Follow-up — Because of the potential association between PPD and mycosis fungoides, patients with atypical presentations and patients who demonstrate clinical or histologic features that suggest a possibility of mycosis fungoides require close clinical follow-up. In particular, the possibility of mycosis fungoides should be considered when patients present with large confluent patches or plaques with reticular arrangements, violaceous hue, or pruritus that have persisted or relapsed over the course of several years [37,137]. Case reports suggest that males may be more likely to have overlapping mycosis fungoides and PPD [59]. (See 'Relationship to mycosis fungoides' above.)

Due to the lack of data on the risk for mycosis fungoides in patients with classic presentations of PPD, the need for follow-up of patients with classic presentations of PPD is unclear. It is generally thought that the risk for mycosis fungoides in this population is low. As a precaution, we perform skin examinations on patients with PPD once yearly.

PREVENTION — No preventive measures have been established for pigmented purpuric dermatoses (PPDs).

SUMMARY AND RECOMMENDATIONS

●Pigmented purpuric dermatoses (PPDs) are uncommon benign cutaneous disorders that are clinically characterized by petechiae or purpura (secondary to erythrocyte extravasation) and localized hyperpigmentation (secondary to hemosiderin deposition in the skin). (See 'Introduction' above.)

●The five major types of PPD are Schamberg disease, purpura annularis telangiectodes, pigmented purpuric lichenoid dermatitis of Gougerot and Blum, lichen aureus, and eczematid-like purpura of Doucas and Kapetanakis. Schamberg disease is the most common type of PPD. PPDs may affect both adults and children. (See 'Epidemiology' above.)

●The pathogenesis of PPDs are poorly understood. Factors such as venous hypertension, systemic diseases, drugs, and contact allergens may contribute to the development of PPDs. Vascular abnormalities, cell-mediated immunity, and humoral immunity have been proposed as pathogenic mechanisms. (See 'Etiology and pathogenesis' above.)

●The diagnosis of PPDs usually can be made through clinical examination. No laboratory abnormalities are associated with PPDs. Skin biopsies are useful for confirming a PPD when the diagnosis is uncertain. (See 'Histopathology' above and 'Laboratory findings' above and 'Diagnosis' above.)

●The response of PPDs to treatment is unpredictable. Most patients with PPD do not require treatment. Treatment is considered for patients who desire treatment due to associated symptoms or patients who are bothered by the cosmetic appearance of lesions. (See 'Treatment' above.)

●Data on the efficacy of treatments for PPD are limited. Our initial approach involves the elimination of drugs or contact allergens that appear to have induced PPD and the use of supportive stockings for patients with concomitant signs of venous stasis. For patients who desire further treatment, we suggest a four to six week course of a medium or high potency topical corticosteroid applied to affected areas (Grade 2C). (See 'First-line interventions' above.)

●For patients who desire treatment, but fail to respond to topical corticosteroid therapy, or for whom topical therapy is impractical due to extensive involvement, we suggest treatment with phototherapy (Grade 2C). Options for treatment include narrowband ultraviolet B (NBUVB) and psoralen plus ultraviolet A (PUVA) phototherapy. (See 'Second-line intervention' above.)

●A number of other treatments have been used for the management of PPD. Pentoxifylline may be beneficial in patients with Schamberg disease. (See 'Other interventions' above.)

●There are no definitive guidelines for the follow-up of patients with PPD. We typically follow patients with atypical clinical features or with histologic features that are suspicious for mycosis fungoides closely due to a possible relationship between mycosis fungoides and PPD. We perform skin examinations on other patients with PPD once yearly. (See 'Prognosis and follow-up' above.)