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CASE REPORT
Year : 2022 | Volume
: 26
| Issue : 2 | Page : 89-91
CD1a-positive dendritic cell-enriched pigmented purpuric dermatosis in association with dyslipidemia
Tiffany Hinojosa1, Daniel J Lewis2, Madeleine Duvic3, Carlos A Torres-Cabala4
1 Center for Clinical Studies, Baylor College of Medicine, Houston, TX, USA
2 School of Medicine, Baylor College of Medicine; Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
3 Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
4 Department of Dermatopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
Correspondence Address:
Dr. Daniel J Lewis
Department of Dermatology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1452, Faculty Tower/Pickens 411, Houston, TX 77030-4008
USA
Source of Support: None, Conflict of Interest: None
DOI: 10.4103/jdds.jdds_85_20
Indeterminate cells (ICs) are dendritic cells (DCs) that share the histologic features of Langerhans cells and macrophages but lack Birbeck granules. It remains unclear whether IC histiocytosis is a separate disease entity or a reactive process. We report the case of a male with an 8-year history of dyslipidemia who developed extensive pigmented purpuric papules. Laboratory studies revealed peripheral monocytosis (8.2%), and two skin biopsies showed a dermal lichenoid lymphohistiocytic infiltrate composed of CD4+ T cells and CD8+ T cells and CD68+CD163+CD1a+Langerin histiocytes. PD-1/PD-L1+T cells were present in the dermis. Our case may help in understanding the pathogenesis of IC histiocytosis, and we hypothesize that expression of CD1a+ dermal DCs and T-cell dysfunction is a reactive process to dyslipidemia.
Keywords: Dendritic cells, dyslipidemia, histiocytosis, indeterminate cells, Langerhans cells, macrophages, T-cell dysfunction
The term “histiocyte” encompasses all the cells of the mononuclear phagocyte system (MPS), which historically has been categorized into monocytes, dendritic cells (DCs), and macrophages on the basis of functional and phenotypic characteristics.[1] At least three DC subsets are present in the skin, including CD1a+ Langerhans cells in the epidermis and two types of dermal DCs (DDCs), expressing either CD1a or CD14.[2]
Indeterminate cells (ICs) are DCs that resemble S100+ CD1a+ Langerhans cells histologically and immunohistochemically but lack Birbeck granules.[3] IC histiocytosis is a rare proliferative disorder of ICs, and several cases of S100-CD1a+ Langerin histiocytosis have been reported.[3] It remains unclear whether IC histiocytosis is a separate disease entity or a reactive process.
Prolonged exposure to a hypercholesterolemic environment has been shown to induce monocytosis and macrophages that promote Th1 responses leading to anti-inflammatory activity.[4] In an attempt to understand the pathogenesis of IC histiocytosis, we report the case of increased CD1a+DDCs associated with PD-1/PD-L1-expressing lymphocytes in a patient with an 8-year history of dyslipidemia. We hypothesize that the expression of CD1a+ DDCs and T-cell dysfunction in our patient may be a reactive process to dyslipidemia.
Case ReportA 54-year-old Caucasian male presented to MD Anderson Cancer Center in November 2013 with a 5-year history of pigmented purpuric papules. He had been originally diagnosed with Schamberg's disease in 2008 after a biopsy of the right lower leg had shown perivascular lymphocytes and extravasated red blood cells.
In March 2013, he reportedly developed several red bumps on his thighs. These lesions then extended up to his waistband, and by June 2013, the lesions had affected the majority of his trunk. The lesions were extremely pruritic and cleared with two separate courses of oral prednisone 50 mg tapered down from 50 mg, but they reappeared each time it was discontinued. The lesions also failed to improve with triamcinolone 0.5% cream.
Physical examination revealed extensive cayenne pepper capillaritis: Erythematous macules and papules with fine scales on the anterior shins, upper back, flank, bilateral hips, waistband area, and both shoulders [Figure 1]. Erythema and scaling were seen bilaterally on the palms, wrists, distal fingers, and plantar and lateral surfaces of the feet. There was no palpable lymphadenopathy.
Figure 1: Clinical appearance of the eruption Erythematous pruritic macules and papules on the left hipHis past medical history was remarkable for an 8-year history of dyslipidemia controlled with atorvastatin 20 mg daily. Laboratory abnormalities included hypercholesterolemia (236 mg/dl, normal <200 mg/dl), hypertriglyceridemia (265 mg/dl, normal <150 mg/dl), and peripheral monocytosis 8.2% (normal 2%–7%). Flow cytometry of the blood was unremarkable.
Skin biopsies of the left hip and right thigh both revealed mild epidermal spongiosis and a lichenoid lymphohistiocytic infiltrate with focal exocytosis of lymphocytes as well as focal vascular dilatation and extravasated red blood cells [Figure 2].
Figure 2: Skin biopsies on the right thigh. (a) A lichenoid lymphohistiocytic infiltrate in dermis (H and E, ×100). (b) Focal vacuolar degeneration and upper dermal extravasated red blood cells (H and E, ×200)Immunohistochemical studies demonstrated a predominance of CD3+ lymphocytes with a CD4:CD8 ratio of 2:1 in the dermis and partial loss of CD7 expression. In addition, the presence of CD8 T cells in the epidermis and dermal lichenoid processes was suggestive of a possible drug reaction [Figure 3]. Molecular studies for T-cell receptor-beta and -gamma gene rearrangements were negative. Macrophage markers CD163 and CD68 were both positive. Although CD1a positive cells with a dendritic appearance were noted in both the epidermis and dermis, Langerin+ cells were not present in the dermis. These findings suggested the presence of epidermal Langerhans cells and CD1a+DDCs. PD-1/PD-L1+ T cells were expressed in the dermis [Figure 4].
Figure 3: Immunohistochemical findings. Studies revealed the lymphocytes to be predominantly CD3+ T-cells (a. CD3, ×100). CD4+ cells outnumbered CD3+ T-cells, suggesting the presence of CD4+ histiocytes (b. CD4, ×100). The CD4:CD8 ratio in the dermis was 2:1 (c. CD8, ×100). CD8 T-cells present in the epidermis and dermal lichenoid processes were suggestive of a possible drug reaction (Inlet, ×200)
Figure 4: Immunohistochemical findings. Macrophage markers CD68 (a, CD68, ×200) and CD163 (b, CD163, ×200) were positive. Although CD1a+ cells with a dendritic appearance were noted in both the epidermis and dermis (c, CD1a, ×200), Langerin+cells were not present in the dermis (d, Langerin, ×200). These findings suggested the presence of epidermal Langerhans cells and CD1a + DDCs. PD-1(e, PD-1, ×200) and PD-L1 (f, PD-L-1, ×200)-positive T cells were present in the dermisWithin 4 months after treatment with topical 10% nitrogen mustard, all lesions had cleared.
DiscussionHistopathologically, CD45+ cutaneous histiocytes are grouped into macrophages (S100-and CD68+, CD163+, or CD14+), DDCs (factor XIIIa+, CD68+, and S100-CD1a-), ICs (S100 + CD1a + Langerin-), and Langerhans cells (S100 + CD1a + Langerin+).[5] However, these characteristics often overlap, making proper classification challenging.[6] In our patient with CD1a+ Langerin histiocytes, we have adopted the most recent term “CD1a + DDCs” used by immunologists, instead of the vague term “IC.”[2]
In our patient, clinical symptoms developed after he was diagnosed with dyslipidemia 8 years before presentation. We hypothesize that the increased percentage of peripheral monocytes and cutaneous infiltration of CD1a+ DDCs were associated with his dyslipidemia. Nine cases of granulomatous pigmented purpuric dermatosis with concurrent hyperlipidemia[7] and a case of IC histiocytosis with modestly elevated total cholesterol and triglycerides support our hypothesis.[8] Hypercholesterolemia induces the overproduction of monocytes that differentiate into DCs and macrophages in the skin. Dyslipidemia may act as a form of persistent antigen stimulation.
In addition, in one report, skin biopsies showing vasculopathy were reported with atorvastatin use in patients with Type 1 diabetes.[9] Furthermore, the histopathologic pattern of CD8+T-cells in the patient is characteristic of a drug reaction. Therefore, the symptoms and histopathologic findings of our patient may be secondary to dyslipidemia or its treatment with atorvastatin. Immunohistochemical studies showed a predominance of CD3+T cells and MPS cells, including CD68 or CD163+ macrophages and CD1a+ DDCs. Both T cells and MPS cells play major roles in innate immunity. Thus, we also hypothesize that increased CD1a+ DDCs in our patient was part of a reactive process that included a T-cell immune response with cells expressing CD4 or CD8 and PD-1/PD-L1. IL-12 induces predominant migration of mature CD1a+ DDCs and efficient CD4+Th cell expansion with a Th1 cytokine profile, resulting in the expansion of functional CD8+ T-cells. Conversely, IL-10 upregulates migration of immature CD14+ DDCs, poor expansion of CD4 + and CD8+ T cells, and favoring of Th responses conducive to the expression of PD-L1.[10],[11]
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that his name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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