Are You Confident of the Diagnosis?

This is a group of common, chronic disorders characterized by speckled, cayenne pepper-like petechiae and orange-brown discoloration. They fall under the category of pigmented purpuric dermatoses (PPD). This is usually the result of capillaritis, which causes petechial hemorrhage. The etiology of the inflammation causing the capillaritis is still unknown. There are five commonly recognized variants, plus other more rare presentations including granulomatous and unilateral. Typically, there are no systemic findings such as underlying vascular insufficiency or other hematologic dysfunction.

There are some common features within the variants. They usually present with symmetric petechiae and/or pigmented macules. These petechiae are not palpable and persist with diascopy. Microscopically there is a perivascular lymphocytic infiltrate in the papillary dermis (Figure 2, Figure 3), swelling of the endothelial cells, erythrocyte extravasation and often, hemosiderin-laden macrophages. The iron deposition is often highlighted in blue using the Perl’s stain (Figure 4).

Figure 1.

Schamberg’s disease.

Figure 2.

H&E showing a perivascular infiltrate with extravasated RBCs. Courtesy of Rosalie Elenitsas, MD

Figure 3.

H&E showing a perivascular infiltrate with extravasated RBCs. Courtesy of Rosalie Elenitsas, MD

Figure 4.

Perl’s iron stain highlighting the iron as blue color. Courtesy of Rosalie Elenitsas, MD

Although there are similarities between them, there are additional features which distinguish each, which will be described below, including the location of the eruption.

Schamberg’s disease (capillaritis), progressive pigmentary dermatosis

This variant is most common in middle-aged and older men, but can be seen in children. It is asymptomatic. Characteristic findings on physical examination are oval to irregular yellow-brown patches with superimposed pinpont macules, often described as “cayenne pepper.” It usually occurs on the lower extremities/ankles and can persist for years (Figure 1).Over time, the individual lesions can become darker and fade but new lesions appear.

Purpura annularis telangiectodes of Majocchi

This variant is most common in adolescents or young adults and is more frequent in women. The morphology is typically a 1-3cm annular plaque with punctate telangiectasias and cayenne pepper petechiae in the border. It is asymptomatic. The lesions can occur for years and can slowly expand.

Pigmented purpuriclichenoid dermatitis of Gougerot and Blum

This rare variant is usually chronic. It is usually seen in men between 40 and 60 years old. Lesions are typically yellow-brown patches with cayenne pepper macules admixed with purpuric red-brown lichenoid papules, often with more generalized invovlement. In general, these lesions are more extensive than the other clinical variants It is often asymptomatic, but can occasionally be pruritic, also known as “itching purpura” Pathologically, a lichenoid infiltrate is observed in addition to the extravasated erythrocytes.

Lichen aureus

This variant is uncommon. Characteristic findings on physical examinatiion usually include a solitary lesion on the lower extremity, and rust to purple brown patches or plaques, often overlying a perforator vein. It is asymptomatic and typically chronic. Pathologically, a lichenoid infiltrate is observed in addition to the extrravasated erythrocytes. One study revealed that dermoscopy shows a coppery-red to brownish background with a partial network of interconnected pigmented lines with round to oval red dots, globules, or patches and gray dots. It is possible that similar findings with dermascopy may be evident with the other forms.

Eczematid-like purpura of Doucas and Kapetanakis eczematous changes

This variant is usually seen in middle-aged and older men, and favors the lower extremities. It is typically pruritic. Physicial examination usually reveals scaly petechial or purpuric macules, papules and patches. Pathologically, epidermal spongiosis with patchy parakeratosisis is seen, in addition to extravasated erythrocytes.

Who is at Risk for Developing this Disease?

The specific etiology is unknown. Risk varies based on the type of lesion; the characteristics are described in the section “Are You Confident of the Diagnosis?”

What is the Cause of the Disease?

Drugs have been reported as etiologies and the detection and avoidance of those possible agents essential for resolution: for example, thiamine, bromine-contaning drugs, carbamazepine, diuretics including furosemide, acetaminophen, non-steroidal anti-inflammatory drugs, raloxifene, interferon-alpha, propyldisulfide, chlordiazepoxide, meprobamate, ampicillin, dietary supplements such as creatine, energy drug ingredients (vitamin B complex, caffeine, taurin). Of note, drug-induced capillaritis can occur even years of taking the drug and clinically is often more generalized and there is no epidermal involvement or lichenoid infiltrate.

Other possible etiologies include chronic infections such as viral hepatitis B or C or odontogenic infections. Of note, drug-induced pigmented purpuric eruptions are more generalized and there is no epidermal involvement or lichenoid infiltrate.

Systemic Implications and Complications

Typically the diagnosis of PPD is made from the clinical examination; however, a biopsy may be necessary to distinguish it from other entities in the differential diagnosis, including small vessel vasculitis, thrombocytopenia, hypergammaglobulinemic purpura of Waldenstrom, mycosis fungoides variant, allergic contact dermatitis, drug eruptions, and dermal hemorrhage secondary to venous hypertension. Pertinent history may also help differentiate these diagnoses as well.

Treatment Options

Topical

Topical corticosteroids (for example, mometasone furoate ointment 0.1% applied daily over 2-3 months, betamethasone diproprionate cream 0.05% twice a day) +/-antihistamines

Topical calcineurin inhibtors, specifically pimecrolimus (twice a day)

Systemic

Pentoxifylline (300mg daily x 8 weeks, 100mg three times a day, or 400mg three times a day x 3 months)

Calcium dobesilate (Cd): 500mg twice a day x 2 weeks then 500mg daily x 3 months

Ascorbic acid (500mg twice a day) + rutoside (50mg twice a day)

Colchicine (0.6mg twice a day)

Griseofulvin (500-750 mg/day x 4 weeks)

Cyclosporin A (starting dose 5 mg/kg/day and tapered at 2 week intervals to 1.5 mg/kg/day)

Physical

Psoralen plus ultravuiolet A (PUVA) (treatment were 3x/week for 29 treatments with a cumulative dose of 200J/cm2; Starting dose 0.5J/cm2 with 40% increments at each visit x 8 exposures; 3x/week with 8-methoxypsoralen at 0.6 mg/kg body weight 2 hours before UVA irradiation, starting dose 0.5-2.5 J/cm2, increasing 0.5-1 J/cm2 with each treatment for a maximum of 6-12 J/cm2 for 4-6 weeks)

Narrow band UVB (3x/week x 5 months then tapered to one treatment every 2 weeks)

Topical photodynamic therapy (5-aminolevulinic acid (ALA) applied under occlusion for 3 hours then irradiated using intense pulsed light with a cutoff filter of 590nm, fluence 18-20J/cm2, energy was double-pulsed at 3.5ms and a pulse duration of 20ms at 3 week intervals; topical methy-ALA under occlusion for 3 hours then irradiated by a red light PDT 1200 lamp 15J/cm2 at 50mW/cms for 7 treatments)

Compression stockings, if exacerbated by increased venous pressure

Optimal Therapeutic Approach for this Disease

Typically, treatment is not necessary unless the lesions are symptomatic. Cosmesis may often be a consideration with treatment options but that can be patient dependent.

If the lesions are pruritic or have significant erythema, topical corticosteroids can be helpful. Care must be taken to review the long-term side effects of topical steroids. If the pruritus is significant, antihistamines can be added for symptomatic relief. Usually, topical steroids are the most effective antiinflammatory; however, there was one case report of lichen aureus recalcitrant to topical corticosteroids and pimecrolimus was inititiated. Marked improvement was seen within 3 weeks of daily application of the medication.

There have been a few case reports where phototherapy has been successful. The mechanism is thought to be immune modulation with altered T lymphocyte activity and concomitant suppression of interleukin-2 production. PUVA has been the most reported; however, more recently both NBUVB and photodynamic therapy have been reported to be successful. With all of the above physical modalities, postinflammatory hyperpigmentation is a concern.

There has been an exciting new therapeutic consideration of supplementation therapy, specifically calcium dobesilate (Cd) as well as ascorbic acid with rutoside (50mg twice a day).

Some evidence reveals increased vascular permeability secondary to defects inthe exracellular matrix. Bioflavinoids inhibit elastase and hyaluronase, which may be a proposed mechanism of action for the benefits of these compounds. Ascorbic acid is an antioxidant which may help reduce vascular permeability, similar to calcium dobesilate, which may also have the same effect secondary to antioxidant properties.

There have also been a few case reports of resolution of Schamberg’s purpura when treated with pentoxifylline in varying doses. After 2-3 months, there was complete resolution of the lesions but this was seen in a limited number of cases. The evidence behind these findings could be that pentoxifylline therapy is associated with a reduction in the expression of adhesion molecules. In addition, this medication may also affect the adherence between T-cells and keratinocytes, thereby decreasing the exocytosis of lymphocytes into the epidermis.

There have only been anecdotal reports of the following drugs being effective in PPD treatment: colchicine, griseofulvin, and cyclosporin A.

If venous insufficiency is a concern, compression stockings can be very useful and prolonged leg dependency should be avoided.

Overall there have been many reports of attempts to treat these dermatoses with various medications; however, most have been unsuccessful, including topical steroids. Those are most effective at relieving symptoms when present. At this time the most interesting and promising is oral rutoside (50mg twice a day) and ascorbic acid (500mg twice a day) and further studies are warrented. Another benefit is that they have minimal side effects. The other modality would be phototherapy; however, patients must be warned of the pssibility of postinflammatory hyperpigmentation, as well as the limitations of insurance coverage.

Patient Management

It is essential to take a careful drug history with particular attention to those drugs listed above. Specific laboratory evaluation would include a complete blood count with differential, coagulation screening, as well as C-reactive protein. If a monoclonal gammopathy is suspected, serum IgG, IgM & IgA levels should be evaluated. A Hess test or Rumpel-Leede test can be considered to assess capillary fragility, which if positive would reveal platelet dysfunction.

It is important to look for signs of chronic infection, including hepatitis as well as other associated systemic diseases such as rheumatoid arthritis. Lastly, based on the history and physical, try to exclude contact dermatitis and chronic venous insufficiency. In general, follow-up is warranted after initial consultation to confirm that the eruption is stable and asymptomatic.

Unusual Clinical Scenarios to Consider in Patient Management

The most concerning aspect of the above differential is that rarely capillaritis has been reported preceding cases of cutaneous T-cell lymphoma. In those instances, a skin biopsy may be necessary to distinguish between the two.

What is the Evidence?

Sardana, K, Sarkar, R, Sehgal, VN. “Pigmented purpuric dermatoses: An overview”. Int J Dermatol. vol. 43. 2004. pp. 482-8. (An overview of PPD including all of the variants including pathology and treatment options as well as a historical perspective.)

Ling, TC, Goulden, V, Goodfield, MJ. “PUVA therapy in lichen aureus”. J Am Acad Dermatol. vol. 45. 2001. pp. 145-6. (A case report of lichen aureus recalcitrant to topical therapy that dramatically improved after eight sessions of twice weekly PUVA treatments.)

Ratnam, KV, Su, WP. “{eters MS. Purpura simplex (inflammatory purpura without vasculitis): a clinicopathologic study of 174 cases”. J Am Acad Dermatol. vol. 25. 1991. pp. 642-7. (A review of 174 cases showing a relationship between prupuric skin eruption and certain drugs in 14% of the cases. Of the patients folllowed, a majority experienced clearing of the lesions.)

Dessoukey, MW, Abdel-Dayem, H, Omar, MF, Al-Suweidi, NE. “Pigmented purpuric dermatosis and hepatitis profile: a report on 10 patients”. Int J Dermatol. vol. 44. 2005. pp. 486-8. (Ten patients were reported to have PPD, 5 of which had antibodies to hepatitic C virus and 2 against hepatitis B virus.)

Hanna, S, Walsh, N, D’Intino, Y, Langley, RG. “Mycosis fungoides presenting as pigmented purpuric dermatitis”. Pediatr Dermatol. vol. 23. 2006. pp. 350-4. (A case report and extensive review of the literature of the previous cases of PPD later diagnosed as mycosis fungoides.)

Kim, SK, Kim, EH, Kim, YC. “Treatment of pigmented purpuric dermatosis with topical photodynamic therapy”. Dermatology. vol. 219. 2009. pp. 184-6. (A report of two cases of PPD recalcitrant to standard therapies showing a moderate response to PDT.)

Lasocki, AL, Kelly, RI. “Narrowband UVB therapy as an effective treatment for Schamberg's disease”. Australas J Dermatol. vol. 49. 2008. pp. 16-18. (A case report of a 33-year-old gentleman with Schamberg's disease that recurred after discontinuation of oral prednisilone. He was started on narrowband UVB three times per week x 5 months. He would remain clear on as little as one treatment every 2 weeks; however, any less than that would cause a recurrence.)

Bohn, M, Bonsmann, G, Luger, TA. “Resolution of lichen aureus in a 10-year-old child after topical pimecrolimus”. Br J Dermatol. vol. 150. 2004. pp. 519-520. (A letter describing a case report of lichen aureus unresponsive to topical steroids. The patient was started on pimecrolimus twice a day and noted significant improvement after 3 weeks. After 10 weeks there was complete clearing, with one relapse that responded to pimecrolimus again, after which no additional lesions were seen.)

Reinhold, U, Seiter, S, Ugurel, S, Tilgen, W. “Treatment of progressive pigmented purpura with oral bioflavonoids and ascorbic acid: An open pilot study in 3 patients”. J Am Acad Dermatol. vol. 41. 1999. pp. 207-8. (A report of 3 patients treated with oral rutoside (50mg twice a day) and ascorbic acid (500mg twice a day) was administered; at the end of the 4-week treatment complete clearance was achieved and remained at the end of 3 months after treatment.)

Panda, S, Malakar, S, Lahiri, K. “Oral pentoxifylline vs. topical betamethasone in Schamberg disease: a comparative randomized investigator-blinded parallel-group trial”. Arch Dermatol. vol. 140. 2004. pp. 491-3. (A randomized, investigator-blinded trial comparing the clinical effectiveness of oral pentoxifylline 400mg three times a day and topical Betamethasone dipropionate cream 0.05% twice a day. In the short term, oral pentoxifylline was found to be more effective than the topical steroid; however, additional long-term studies are necessary.)