Granulomatous Changes Associated With Pigmented Purpuric Dermatosis

Pigmented purpuric dermatoses (PPDs) are a group of common chronic disorders characterized by speckled, cayenne pepper–like petechiae and orange-brown discoloration of the skin resulting from capillaritis.¹ Pigmented purpuric dermatoses typically occur in the absence of underlying vascular insufficiency or other hematologic dysfunction. The 5 well-known clinicopathologic variants of PPD include Schamberg disease; purpura annularis telangiectodes of Majocchi; pigmented purpuric lichenoid dermatitis of Gougerot and Blum; eczematoidlike purpura of Doucas and Kapetanakis; and lichen aureus.² All PPDs share common characteristic clinical and histologic features. Clinically, patients generally present with symmetric petechiae and/or pigmented macules. All 5 PPD variants share similar histologic findings, including a vasculocentric lymphocytic infiltrate in the papillary dermis, swelling of the endothelial cells, erythrocyte extravasation, and often hemosiderin-laden macrophages.¹ Despite these clinical and histopathologic similarities, each variant contains additional distinctive features, such as telangiectasia (purpura annularis telangiectodes of Majocchi), a lichenoid infiltrate (pigmented purpuric lichenoid dermatitis of Gougerot and Blum), eczematous changes (eczematoidlike purpura of Doucas and Kapetanakis), and marked hemosiderin deposition (lichen aureus).

Granulomatous pigmented purpuric dermatosis (GPPD) is a rare variant of PPD.^3-7 Clinically, these lesions appear similar to other PPDs; however, in addition to the characteristic changes associated with conventional PPD, histologic examination of GPPD reveals a granulomatous inflammatory reaction pattern. Although the pathogenesis of GPPD is not well understood, its association with hyperlipidemia may suggest a granulomatous response to capillaritis mediated by lipid deposition in the microvasculature.^6,7

We present 3 cases of GPPD and provide a review of the literature. In all of our patients, biopsy specimens were fixed in 10% buffered formalin and embedded in paraffin by standard methodologies, and all stains were performed on sections by standard methodologies. Based on a PubMed search of articles indexed for MEDLINE using the terms granulomatous pigmented purpuric dermatosis, sarcoidosis, pigmented purpuric dermatosis, granulomas, and pigmented purpuric dermatosis, we review 5 additional reports describing 10 total patients.^3-7

Case Reports

Patient 1

A 9-year-old white boy presented with a 3-cm asymptomatic light brown patch with a nonblanching violaceous center on the right posterior thigh that was studded with pinpoint yellow papules (Figure, A). The lesion appeared 3 to 4 years prior to presentation but had become progressively darker and centrally indurated over the last 2 years. The patient and his mother denied any history of trauma to the area. His medical history was unremarkable, and his current medications included fish oil and multivitamin tablets.

Histologic examination of a punch biopsy specimen taken from the center of the lesion revealed a lichenoid lymphohistiocytic infiltrate with marked red blood cell (RBC) extravasation and associated hemosiderin-laden macrophages. The lymphocytes comprising this infiltrate lacked cytologic atypia and exhibited minimal epidermotropism (Figure, B). Additionally, there was a superficial and deep perivascular mononuclear inflammatory infiltrate intermixed with numerous small granulomas comprised ofepithelioid histiocytes in the mid and deep dermis (Figure, C). Periodic acid–Schiff, acid-fast bacilli (AFB), and Fite stains were negative for organisms. Polarization was negative for refractile foreign material. Due to the patient’s age, no treatment was performed, and the lesion remains unchanged 1 year after biopsy.

Patient 2

A 49-year-old white woman presented with a 2-cm yellow-brown patch with a faint, nonblanchable, violaceous center on the right lateral thigh of 4 months’ duration. The patch initially appeared as a small asymptomatic purple papule. The patient denied any history of trauma to the area. A purified protein derivative (tuberculin) skin test was negative at the time of examination. The patient’s medical history was remarkable for renal calculi. Her current medications included progesterone; estradiol; lansoprazole; prenatal vitamins; vitamins C and E; zinc; and calcium. The patient had no family history of sarcoidosis. Complete blood cell count, urinalysis, liver function tests, and angiotensin-converting enzyme levels were unremarkable. Pulmonary function tests were normal, and there was no evidence of sarcoidosis on chest radiography. Initial biopsy of the lesion revealed a perivascular and interstitial lymphohistiocytic infiltrate with abundant extravasated RBCs in the papillary dermis (Figure, D). Similar to patient 1, the infiltrate lacked cytologic atypia and did not involve the overlying epidermis. There was perivascular granulomatous inflammation in the mid dermis (Figure, E). Periodic acid–Schiff, Warthin-Starry, and AFB stains were negative for organisms. Polarization was negative for refractile foreign material.

The lesion was treated with clobetasol propionate ointment 0.05% twice daily for 6 weeks with transient improvement, but the lesion recurred upon treatment cessation. Subsequent treatment with intralesional triamcinolone resulted in slight improvement of the lesion. A therapeutic trial of targeted pulsed dye laser treatment was ineffective. The lesion gradually increased in size over the next year with no therapy, and a repeat biopsy revealed a lichenoid lymphohistiocytic infiltrate with abundant extravasated RBCs consistent with persistent PPD. A granulomatous infiltrate was not evident in the superficial shave biopsy specimen.

Patient 3

A 75-year-old white woman presented with scattered, speckled, cayenne pepper–like, red-brown macules on the legs. Two years prior to presentation, a few scattered symmetrical macules appeared on the dorsal aspects of the feet, which gradually increased in number to form larger confluent patches that spread to the lower legs. The patient denied itching or burning but reported that the patches became painful when scratched and were aggravated by sun exposure. Her medical history was remarkable for asthma, chronic renal insufficiency, coronary artery disease, Barrett esophagus, obstructive sleep apnea, hypothyroidism, renal calculi, type 2 diabetes mellitus, and hyperlipidemia. Her current medications included carvedilol, valsartan, levothyroxine, aspirin, clopidogrel, furosemide, nitrofurantoin, temazepam, insulin, ezetimibe-simvastatin, and lansoprazole. Computed tomography of the chest revealed no signs of sarcoidosis. Pulmonary function tests revealed moderate obstructive lung disease. An ophthalmology examination showed no evidence of sarcoidosis. Laboratory results revealed an elevated glucose, blood urea nitrogen, creatinine, and triglyceride levels, as well as low hematocrit and vitamin D levels. Urinalysis, thyroid-stimulating hormone (thyrotropin) test, liver function tests, angiotensin-converting enzyme test, hepatitis B surface antigen, and IFN-g release assay were normal.

Histologic examination of a punch biopsy specimen revealed an inflammatory infiltrate confined to the papillary dermis. This infiltrate was comprised of an admixture of lymphocytes and histiocytes in a perivascular distribution with associated RBC extravasation and intimately associated granulomas (Figure, F). Additional inflammation in the deeper aspects of the dermis was not identified. Periodic acid–Schiff, AFB, and Fite stains were negative for organisms. Polarization was negative for refractile foreign material.

A 3-cm asymptomatic light brown patch with a nonblanching violaceous center on the right posterior thigh that was studded with pinpoint yellow papules (A). Lichenoid lymphohistiocytic infiltrate in the papillary dermis with marked red blood cell extravasation (B)(H&E, original magnification ×20). Superficial and deep perivascular mononuclear inflammatory infiltrate intermixed with numerous small granulomas comprised of epithelioid histiocytes in the mid and deep dermis (C)(H&E, original magnification ×20). Perivascular and interstitial lymphohistiocytic infiltrate with abundant extravasated red blood cells in the papillary dermis (D)(H&E, original magnification ×10). Perivascular lymphohistiocytic inflammation with epithelioid granulomas in the mid dermis (E)(H&E, original magnification ×20). Lymphohistiocytic inflammation in the papillary dermis comprised of an admixture of lymphocytes and histiocytes in a perivascular distribution with associated red blood cell extravasation and intimately associated granulomas (F)(H&E, original magnification ×20).

The patient was treated with topical steroids and minocycline 50 mg twice daily without improvement. The lesions improved after the patient underwent treatment with oral corticosteroids for pulmonary disease.