Coming to terms with Louis Brocq and his diagram: Pityriasis lichenoides 2018

By Warren R. Heymann, MD
July 16, 2018

 

As a first-year dermatology resident in 1980, I struggled with the concept of parapsoriasis. In trying to conceptualize the process, I recall being distressed after seeing Louis Brocq’s diagram from his classic paper, “Les parapsoriasis”, published in 1902 — Would I ever understand this? What is the relationship to Cutaneous T-cell lymphoma? How did he come up with this schematic? Was he brilliant or insane?

For some quick answers: Louis Anne Jean Brocq (1856-1928), Head of the Department of Dermatology at Hôpital St. Louis, was a superlative clinical scholar, who ranked first in his medical school examinations. According to Cribier, “He had the intuition that parapsoriasis lichenoides and large plaque parapsoriasis were close to mycosis fungoides.” It is not surprising that his famed students were Lucien-Marie Pautrier and Achille Civatte, (1,2), both offering seminal research in mycosis fungoides. Regarding the schematic itself, although I cannot comprehend what Brocq was thinking about the outlying disorders, his recognition that the three central entities shaded in gray (parapsoriasis en plaque, guttate parapsoriasis, and parapsoriasis lichenoides) as being related to one another, and to mycosis fungoides, was visionary.

This commentary will focus on new observations related to pityriasis lichenoides (PL).

The PL spectrum ranges from pityriasis lichenoides et varioliformis acuta (PLEVA, Mucha-Habermann disease), manifested by acute ulceronecrotic lesions (especially in the febrile ulcerative variant) to the scaly papules of pityriasis lichenoides chronica (PLC of Juliusberg) that often resolve with hypopigmentation in patients of color. I use the term “pityriasis lichenoides subacuta” for cases in the middle of the spectrum with overlapping features, however, that is not mentioned in the literature.

The etiology of PL is unknown. There are three main theories: 1) an inflammatory response to infectious agents, especially viruses; 2) an inflammatory reaction to a T-cell dyscrasia; and 3) an immune complex-mediated hypersensitivity vasculitis. CD8+ T cells predominate in PLEVA; either CD4+ or CD8+ T-cells have been reported in PLC. Clonality may be observed. T-cells express the adhesion molecule lymphocyte-associated antigen (CLA) and chemokine receptor CXCR3. Plasmacytoid dendritic cells (PDCs) are a major component of the inflammatory infiltrate in PL, which leads to type I interferon production, ultimately leading to a cytotoxic effect of the basement membrane, characterized by necrotic keratinocytes. (3)
 
According to Permanyer et al, “lymphatic endothelial cells (LECs) support T cell survival, induce tolerance to self-antigens, inhibit exaggerated T cell proliferation during immune response and maintain T cell memory. Reciprocally, leukocytes impact LEC biology: lymphatic vessel permeability depends on DCs while lymphocytes regulate LEC proliferation during inflammation. Altogether, these novel results provide important insights on intimate connections between LECs and leukocytes that contribute to the understanding of immune responses. (4)

Magro et al presented 10 cases of a PL-like drug reaction histologically demonstrating marked parakeratosis, epidermotropism of mildly atypical lymphocytes, psoriasiform hyperplasia, dyskeratosis, hemorrhage, and reduced expression of CD7 and CD62. The most frequently implicated drugs were antidepressants and statins. The outcome was known in seven of the 10 cases — all resolved with discontinuation of the presumed offending drug. The authors concluded: “the onset of lesions clinically and histologically resembling PL in an older individual should lead one to consider a drug-based trigger.” (5)

PL is predominantly a dermatosis of the young.  In their study of 75 patients, 50 (67%) patients were diagnosed with PLC, 22 (29%) with PLEVA, and 3 (4%) with PLC and PLEVA features. Mean ± standard deviation age at onset was 12 ± 13 years (median 8 years). Disease duration was significantly shorter for patients with PLEVA (35 ± 35 months) than for those with PLC (at least 78 ± 48 months). At long-term follow-up, 23 of 28 (82%) patients with PLC and 3 of 16 (19%) with PLEVA had active disease. None progressed to lymphomatoid papulosis or cutaneous T-cell lymphoma. Ten of 23 active PLC cases had residual pigmentary change independent of race lasting at least 35 ± 20 months. (6)
 
Although rare, PL may evolve into cutaneous T-cell lymphoma (CTCL). Zaaroura et al reported three such cases from 58 with PL. They observed that a prolonged clinical course, appearance of patches and larger plaques, markedly increased lymphocytic nuclear atypia, significant diminution of apoptotic keratinocytes and CD7+ and CD8+ lymphocytes, and clonal T-cell receptor gene rearrangement may serve as clues. (7) Borra et al opine that the distinction between PLEVA and PLC is artificial, and the term PL should be used alone. The note that “conventional” PL is a completely benign condition, however, atypical PL (APL), which demonstrates an aberrant phenotype, may be a precursor of, or have the potential to evolve into, mycosis fungoides (MF). It is also conceivable that such cases are MF from the outset. (8) Lymphomatoid papulosis, and other CD30+ lymphoproliferative disorders, share clinical features with PL.

Therapy for PL is relatively unsatisfactory, with phototherapy (NBUVB, PUVA), antibiotics (tetracyclines, macrolides), and methotrexate being first line treatments. The realization that type I interferons may be pathogenic, raises the possibility for targeted anti-type I interferon agents such as rontalizumab or sifalimumab, that are being studied for autoimmune rheumatologic disorders. (9)

It has been 116 years since Brocq presented his diagram to the dermatological world. The precise relationship of PL to CTCL is still debated. I hope that by 2134 the future editor of DI&I will be far more insightful than I am today.

1. Cribier B. Louis Ann Jean Brocq (1856-1928). In Löser C, Plewig G, Burgdorf WHC (eds). Pantheon of Dermatology. Springer, Berlin Heidelberg, 2013, pp 125-9.
2. Ackerman AB, Papakonstantinou A. Brocq’s graphic of parapsoriasis: Interpretation through illustrations of his student, Achille Civatte. Dermatopathology: Practical & Conceptual; 2000: 6: 3 (accessed via Derm 101).
3. Karouni M, et al. Possible role of plasmacytoid dendritic cells in pityriasis lichenoides. Clin Exp Dermatol 2018; 43: 404-9.
4. Permanyer M, et al. Dendritic cells, T cells and lymphatic: Dialogues in migration and beyond. Curr Opin Immunol 2018; 53: 173-9.
5. Magro C, et al. Pityriasis lichenoides-like drug reaction: A clinical histopathologic study of 10 cases. Dermatol Online J 2017; Nov 15; 3 (11).
6. Zang JB, et al. Pityriasis lichenoides: Long-term follow-up study. Pediatr Dermatol 2018; 35: 213-9.
7. Zaaroura H, et al. Relationship between pityriasis lichenoides and mycosis fungoides.: A clinicopathological, immunohistochemical, and molecular study. Am J Dermatopathol 2018; 40: 409-14.
8. Borra T, et al. Pityriasis lichenoides, atypical pityriasis lichenoides, and related conditions: A study of 66 cases. Am J Surg Pathol 2018. May 30 [Epub ahead of print]
9. Muskardin TLW, Niewold TB. Type I interferon in rheumatic diseases. Nat Rev Rheumatol. 2018; 14:214-228.

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