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parapsoriasis

What is parapsoriasis

Parapsoriasis refers to one of a group of skin disorders that are characterized primarily by their resemblance to psoriasis (red, scaly lesions), rather than by their underlying causes 1. However, parapsoriasis includes several inflammatory cutaneous diseases that are unrelated with respect to pathogenesis, histopathology, and response to treatment 2. Because of the variation in clinical presentation and a lack of a specific diagnostic finding on histopathology, a uniformly accepted definition of parapsoriasis remains lacking 2.

In 1902, Brocq initially described 3 major entities that fit the parapsoriasis description 3:

  1. Pityriasis lichenoides (acuta and chronica)
  2. Small plaque parapsoriasis
  3. Large plaque parapsoriasis (parapsoriasis en plaque)

Neoplasms can devleop from parapsoriasis 1. For example, it can develop into cutaneous T-cell lymphoma. Mycosis fungoides is the most common type of cutaneous T-cell lymphoma. It is a cutaneous lymphoma that originates in the peripheral epidermotropic T-cells, specifically the memory T-cells (CD45RO+), which express the T-cell receptor (TCR) and CD4+ immunophenotype 4. The earliest lesion seen in mycosis fungoides is an erythematous, or brownish scaly patch, which may show slight atrophy. Single or multiple lesions of variable diameters and locations develop, often in covered areas and particularly in the gluteal region and on the proximal thighs. The term sometimes given to them of “plaque parapsoriasis” is a misnomer because the lesions are actually patches. “Small-plaque” parapsoriasis and “large-plaque” parapsoriasis are set apart based on the clinical and histopathological correlation5. Small plaque parapsoriasis lesions are 2 to 6 cm in diameter, located on the trunk, and do not present atrophy or telangiectasia. Small-plaque parapsoriasis shows minimum potential to become infiltrated or tumoral.Large-plaque parapsoriasis presents with lesions that are larger than 6 cm in diameter, with signs of atrophy and poikiloderma. They are seen on the trunk, gluteal region, proximal extremities and mammary region. The histopathological picture may resemble mycosis fungoides, in fact, large-plaque parapsoriasis does progress to frank mycosis fungoides (i.e infiltrated and/or tumoral lesions) in around 7.5% to 14% of cases 5.

Pityriasis lichenoides (acute and chronic)

Pityriasis lichenoides variants describe scaly dermatoses with necrotic papules that are clinically and histologically different from parapsoriasis. These diseases generally are benign and undergo spontaneous resolution but, at times, may have a protracted course.

Large plaque and small plaque parapsoriasis

Current terminology of parapsoriasis refers to 2 disease processes that are caused by T-cell–predominant infiltrates in the skin. These disease processes are large plaque parapsoriasis and small plaque parapsoriasis.

As the nomenclature and description of the disease spectrum under the descriptive term parapsoriasis evolved, the primary focus has been on the distinction of whether the disorder progresses to mycosis fungoides or cutaneous T-cell lymphoma (CTCL). Small plaque parapsoriasis is a benign disorder that rarely if ever progresses. Large plaque parapsoriasis is more ominous in that approximately 10% of patients progress to mycosis fungoides or cutaneous T-cell lymphoma 6. Controversy exists currently in the classification of large plaque parapsoriasis because some believe it is equivalent to the earliest stage of cutaneous T-cell lymphoma, the patch stage 7. A meta-analysis from 2016 supports a risk of transformation to early cutaneous T-cell lymphoma 8.

The duration of parapsoriasis can be variable. Small plaque disease lasts several months to years and can spontaneously resolve. Large plaque disease is chronic, and treatment is recommended because it may prevent progression to cutaneous T-cell lymphoma.

El-Darouti et al 9 reported on a 7-year study of a hypopigmented disorder that the researchers believe should be classified as a new variant of parapsoriasis en plaque.

No clear cause for small plaque or large plaque parapsoriasis is known, and no specific association has been made with contact exposure or infections.

Parapsoriasis causes

The initiating cause of parapsoriasis is unknown, but the diseases likely represent different stages in a continuum of lymphoproliferative disorders from chronic dermatitis to frank malignancy of cutaneous T-cell lymphoma.

Primary cutaneous lymphomas are the second most common extranodal non-Hodgkin lymphomas 10. They may be of either T cell, B cell, or NK cell origin. Cutaneous T cell lymphomas (CTCL) comprise a group of heterogeneous lymphomas which clinically differ from systemic lymphomas, even though they might show similar histology 11.

Small plaque parapsoriasis

Small plaque parapsoriasis likely is a reactive process of predominantly CD4+ T cells. Genotypic pattern observed in small plaque parapsoriasis is similar to that observed in chronic dermatitis, and the pattern of clonality of T cells is consistent with the response of a specific subset of T cells that have been stimulated by an antigen. Multiple dominant clones can be detected by polymerase chain reaction (PCR) of T-cell receptor gene usage, which supports a reactive process. Lymphocytes do not show histologic atypia to suggest malignant transformation. Southern blot analysis of T-cell receptor genes from parapsoriasis does not identify a dominant clone of T cells.

Some physicians believe that small plaque parapsoriasis is an abortive T-cell lymphoma; however, no clear distinguishing evidence, such as genetic changes (eg, TP53 mutations) observed in other malignancies, exists to support this contention 12. Nevertheless, a hint to the verity of this hypothesis is the recent identification of increased telomerase activity in T cells from CTCL at low-grade stages, high-grade lymphoma, and parapsoriasis, which is activity not exhibited in normal T cells. A better understanding is likely to develop from further molecular characterization 13.

Large plaque parapsoriasis

Large plaque parapsoriasis is a chronic inflammatory disorder, and the pathophysiology has been speculated to be long-term antigen stimulation. This disorder is associated with a dominant T-cell clone, one that may represent up to 50% of the T-cell infiltrate. If the histologic appearance is benign, without atypical lymphocytes, classification of large plaque parapsoriasis is made. If atypical lymphocytes are present, many would classify such patients as having patch stage cutaneous T-cell lymphoma.

In one study, human herpesvirus type 8 was detected in up to 87% of skin lesions of large plaque parapsoriasis. This is the first association of a specific infectious agent with large plaque parapsoriasis, and the significance is unclear. Further studies are important to determine the significance of this finding 14.

The close relationship between large plaque parapsoriasis and mycosis fungoides is highlighted by the detection of TOX expression, a new marker that has been described to be frequently detected in the abnormal T cells in mycosis fungoides. In one study, large plaque parapsoriasis has expression of TOX similar to that of mycosis fungoides 15.

Parapsoriasis symptoms

Onset of parapsoriasis is indolent. It develops from a few patches and becomes more visible over a protracted period of time. Additional lesions develop progressively in some individuals.

Small plaque parapsoriasis can last months to several years; the disease often resolves spontaneously. Lesions of small plaque parapsoriasis are well-circumscribed, slightly scaly, light salmon-colored patches that measure less than 5 cm in diameter and are scattered over the trunk and extremities. Digitate pattern is a distinctive form of small plaque disease that consists of palisading elongated fingerlike patches that follow the dermatome and are most prominently displayed on the lateral thorax and abdomen 16.

Large plaque parapsoriasis is a chronic disorder that manifests in an indolent manner and progresses over many years, sometimes decades. It may progress to mycosis fungoides, a cutaneous T-cell lymphoma, after an indeterminate number of years.

Large plaque parapsoriasis manifests as faint erythematous patches with arcuate geographic borders. Each lesion often is greater than 6 cm in diameter. Lesions are scattered on the proximal extremities and the trunk and often show a bathing-suit distribution. Surfaces of the lesions have a faint red-to-salmon color; show flaky thin scales; and have an atrophic, cigarette-paper or tissue-paper, wrinkling quality.

Large plaque parapsoriasis does not enter remission without treatment.

Parapsoriasis diagnosis

Laboratory studies

A complete blood cell count with differential should be performed, and a high lymphocyte count or the presence of Sézary cells suggests mycosis fungoides/cutaneous T-cell lymphoma.

Skin biopsy

Skin biopsy with immunophenotyping analysis and gene rearrangement studies should be performed.

Histologic findings

Histopathology of small plaque parapsoriasis shows a mild superficial perivascular lymphocytic infiltrate with a nonspecific inflammatory infiltrate of CD4+ and CD8+ T cells. However, CD4+ T cells are predominant. The epidermis may show mild spongiosis, focal hyperkeratosis, scale crust, parakeratosis, and occasional exocytosis. Often, the pattern is not diagnostic and is nonspecific. Lymphocytes are small and do not show atypical features.

In large plaque parapsoriasis, a superficial dermal inflammatory infiltrate consists predominantly of lymphocytes. Numerous lymphocytes abut the dermal-epidermal junction and single lymphocytes can be observed in the epidermis. Lymphocytes are generally small and do not show atypical nuclei. Blood vessels are dilated, and melanophages can be present. The epidermis shows flattening of the rete ridges when epidermal atrophy is prominent on clinical examination. Acanthosis of the epidermis and irregular hyperkeratosis of the cornified layer are present. In contrast to small plaque parapsoriasis, spongiosis is absent.

Gene rearrangement studies can assist in excluding mycosis fungoides or cutaneous T-cell lymphoma.

Parapsoriasis treatment

Parapsoriasis can be managed conservatively on the basis of symptoms, and often, topical treatment is effective. A novel treatment of parapsoriasis reported in 2018 is hydrogen-water bathing. This modality proposes water with increased reactive oxygen scavenging properties as the mechanism. In a small study in which parapsoriasis patients were bathed twice weekly over 8 weeks, four of six showed partial responses and two had complete remission. The treatment was well tolerated 17.

Small plaque parapsoriasis

Small plaque parapsoriasis usually is asymptomatic. Treatment should be based on alleviation of symptoms associated with scaliness, and patients should be reassured of the benign self-limiting nature of the disease.

Emollients may be sufficient to treat scaliness; however, a trial of midpotency topical steroids (class 3-5) may lead to greater clinical responsiveness.

Phototherapy is effective in treating lesions that are widely scattered. Broad- or narrow-band UV-B can be effective and can lead to remission 18. More recalcitrant presentations can be treated with psoralen and long-wave ultraviolet radiation (PUVA).

Annual follow-up is recommended. An increase in the number of lesions, an increase in the size of lesions, or the development of induration or epidermal atrophy should prompt a repeat skin biopsy to consider a diagnosis of mycosis fungoides in evolution.

Large plaque parapsoriasis

Large plaque parapsoriasis should be treated, because treatment may prevent progression to mycosis fungoides (cutaneous T-cell lymphoma). Therapy includes mid- to high-potency topical steroids (class 2-4), topical nitrogen mustard, and topical carmustine (BCNU). Patients using topical treatment need follow-up every 2-3 months 19.

Phototherapy with either broad- or narrow-band UV-B or PUVA can be effective in inducing remission. Phototherapy requires an evaluation to response after every 8-12 visits or monthly.

Large plaque parapsoriasis requires closer follow-up than small plaque parapsoriasis. Follow-up frequency is determined by the treatment modality used. Follow-up every 6 months is recommended. Increasing number of lesions, increase in lesion size, or the development of induration or epidermal atrophy should prompt a repeat skin biopsy to consider a diagnosis of mycosis fungoides in evolution. If patients remit or do not desire treatment, follow-up is still recommended to assess for recurrence or progression.

Consult with a dermatologist specializing in cutaneous lymphoma to coordinate medical care if progression to mycosis fungoides (cutaneous T-cell lymphoma) occurs.

Parapsoriasis prognosis

Small plaque parapsoriasis may persist in a stable pattern for years to decades and then resolve spontaneously. A small number of cases may progress to mycosis fungoides.

Large plaque parapsoriasis remains indolent for many years. The disease may progress to cutaneous T-cell lymphoma (CTCL) with transformation of lymphocytes from benign small size to larger atypical lymphocytes. The 5-year survival rate, however, still remains high and is greater than 90%.

References
  1. Parapsoriasis: a complex issue. Skinmed. 2007 Nov-Dec;6(6):280-6. https://www.ncbi.nlm.nih.gov/pubmed/17975354
  2. Parapsoriasis. https://emedicine.medscape.com/article/1107425-overview
  3. The nosology of parapsoriasis. J Am Acad Dermatol. 1981 Oct;5(4):373-95. https://www.ncbi.nlm.nih.gov/pubmed/7026622
  4. Hossain C, Jennings T, Duffy R, Knoblauch K, Gochoco A, Chervoneva I, Shi W, Alpdogan SO, Porcu P, Pro B, Sahu J. The histological prevalence and clinical implications of folliculotropism and syringotropism in mycosis fungoides. Chin Clin Oncol. 2019 Feb;8(1):6.
  5. Pimpinelli N, Olsen EA, Santucci M, Vonderheid E, Haeffner AC, Stevens S, Burg G, Cerroni L, Dreno B, Glusac E, Guitart J, Heald PW, Kempf W, Knobler R, Lessin S, Sander C, Smoller BS, Telang G, Whittaker S, Iwatsuki K, Obitz E, Takigawa M, Turner ML, Wood GS., International Society for Cutaneous Lymphoma. Defining early mycosis fungoides. J. Am. Acad. Dermatol. 2005 Dec;53(6):1053-63.
  6. Kikuchi A, Naka W, Harada T, Sakuraoka K, Harada R, Nishikawa T. Parapsoriasis en plaques: its potential for progression to malignant lymphoma. J Am Acad Dermatol. 1993 Sep. 29(3):419-22.
  7. Olsen E, Vonderheid E, Pimpinelli N, et al. Revisions to the staging and classification of mycosis fungoides and Sezary syndrome: a proposal of the International Society for Cutaneous Lymphomas (ISCL) and the cutaneous lymphoma task force of the European Organization of Research and Treatment of Cancer (EORTC). Blood. 2007 Sep 15. 110(6):1713-22.
  8. Sibbald C, Pope E. Systematic review of cases of cutaneous T-cell lymphoma transformation in pityriasis lichenoides and small plaque parapsoriasis. Br J Dermatol. 2016 Oct. 175 (4):807-9.
  9. El-Darouti MA, Fawzy MM, Hegazy RA, Abdel Hay RM. Hypopigmented parapsoriasis en plaque, a new, overlooked member of the parapsoriasis family: a report of 34 patients and a 7-year experience. J Am Acad Dermatol. 2012 Dec. 67(6):1182-8.
  10. Vaidya T, Zulfiqar H, Badri T. Mycosis Fungoides. [Updated 2019 Jun 24]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2019 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK519572
  11. Scarisbrick JJ, et al. The PROCLIPI international registry of early-stage mycosis fungoides identifies substantial diagnostic delay in most patients. Br. J. Dermatol. 2018 Sep 29
  12. Baskan EB, Tunca B, Cecener G, et al. Analysis of p53 gene mutations in parapsoriasis. J Eur Acad Dermatol Venereol. 2006 Aug. 20(7):882-3.
  13. Wu K, Lund M, Bang K, Thestrup-Pedersen K. Telomerase activity and telomere length in lymphocytes from patients with cutaneous T-cell lymphoma. Cancer. 1999 Sep 15. 86(6):1056-63.
  14. Kreuter A, Bischoff S, Skrygan M, Wieland U, Brockmeyer NH, Stücker M. High association of human herpesvirus 8 in large-plaque parapsoriasis and mycosis fungoides. Arch Dermatol. 2008 Aug. 144(8):1011-6.
  15. McGirt LY, Degesys CA, Johnson VE, Zic JA, Zwerner JP, Eischen CM. TOX expression and role in CTCL. J Eur Acad Dermatol Venereol. 2016 Jun 26.
  16. Lewin J, Latkowski JA. Digitate dermatosis (small-plaque parapsoriasis). Dermatol Online J. 2012 Dec 15. 18(12):3.
  17. Zhu Q, Wu Y, Li Y, Chen Z, Wang L, Xiong H, et al. Positive effects of hydrogen-water bathing in patients of psoriasis and parapsoriasis en plaques. Sci Rep. 2018 May 23. 8 (1):8051.
  18. Herzinger T, Degitz K, Plewig G, Rocken M. Treatment of small plaque parapsoriasis with narrow-band (311 nm) ultraviolet B: a retrospective study. Clin Exp Dermatol. 2005 Jul. 30(4):379-81.
  19. Lindahl LM, Fenger-Gron M, Iversen L. Topical nitrogen mustard therapy in patients with mycosis fungoides or parapsoriasis. J Eur Acad Dermatol Venereol. 2013 Feb. 27(2):163-8.
Health Jade Team

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