Pityriasis Lichenoides Chronica in a Patient With Ankylosing Spondylitis Treated With Etanercept.

BACKGROUND: Pityriasis lichenoides chronica, a papulosquamous disorder often considered a subtype of pityriasis lichenoides. It is considered a clonal T-cell disorder, which may be associated with cutaneous T-cell lymphoma that may develops in response to foreign antigens. CASE PRESENTATION: We present a 38-year-old male patient with ankylosing spondylitis who was on treatment with etanercept. After 8 weeks of treatment, the patient presented with scaly erythematous papules, on the back and arms. He was diagnosed clinically with pityriasis lichenoides chronica. CONCLUSION: Pityriasis lichenoides chronica should be included among the broad clinical spectrum of chronic inflammatory skin diseases which may occur during treatment with TNF-alpha antagonists. J Drugs Dermatol. 2020;19(5): doi:10.36849/JDD.2020.2191.

Pityriasis Lichenoides, Atypical Pityriasis Lichenoides, and Related Conditions: A Study of 66 Cases.

Pityriasis lichenoides (PLs) is an uncommon skin disease of unknown etiology. In recent years, an atypical form of PL has been described, showing overlapping features with mycosis fungoides (MF) and lymphomatoid papulosis. We studied 66 patients with an initial histopathologic diagnosis of PL (M:F=34:32; median age, 25 y; range, 7 to 85 y). According to clinical and phenotypic features, cases were classified into 4 categories: (1) Conventional PL (characteristic clinical features of PL without phenotypic aberrations) (n=20; M:F=8:12; median age, 37 y; range, 9 to 74 y); (2) Atypical form of PL (characteristic clinical features of PL with phenotypic aberrations) (n=25; M:F=16:9; median age, 21 y; range, 7 to 72 y). Four of these patients subsequently developed MF; (3) Lymphomatoid papulosis (waxing and waning lesions and positivity for CD30) (n=10; M:F=4:6; median age, 41 y; range, 16 to 83 y); (4) MF (clinical features typical of MF) (n=11; M:F=6:5; median age, 17 y; range, 8 to 85 y). Molecular analyses of clonality of the infiltrate did not reveal relevant differences among these 4 groups. Our study suggests that patients with an initial histopathologic diagnosis of PL may belong to different groups, showing that clinicopathologic correlation and complete phenotypic analyses are paramount in order to achieve proper classification. Although the relationship between PL and MF is yet a matter of debate, at the present state of knowledge, patients with a clinicopathologic presentation consistent with PL but with aberrant phenotypic features should be monitored in order to detect a possible evolution into MF.

Possible role of plasmacytoid dendritic cells in pityriasis lichenoides.

BACKGROUND: Plasmacytoid dendritic cells (pDCs) and their product, type I interferons (IFNs), have been implicated in the pathogenesis of several skin disorders characterized by an interface dermatitis (ID) pattern, such as lichen planus (LP). A type I IFN signature has previously been documented in pityriasis lichenoides (PL). Although pDCs are known to be the main source and most potent producers of local type I IFNs, their role in PL has not been investigated. AIM: To investigate the role of pDCs in PL. METHODS: In total, 20 cases of PL and 20 comparable cases of LP were immunohistochemically tested for pDC occurrence and type I IFN production using anti-blood-derived dendritic cell antigen-2 (BDCA2; a specific pDC marker) and anti-myxovirus protein A (anti-MxA) antibodies (indirect marker of pDC activity), respectively. MxA is a well-established surrogate marker for local type 1 IFN production. A semiquantitative scoring system was used. RESULTS: pDCs were present in all 40 cases with no statistically significant difference between the two groups. MxA expression was intense and diffuse in the majority of PL and LP cases. CONCLUSIONS: pDCs constitute a central component of the inflammatory infiltrate in PL, suggesting that PL shares with the other entities that exhibit an ID a common pDC-driven process through type I IFN production, which ultimately leads to the cytotoxic attack.

Skin and coeliac disease, a lot to think about: a case series.

Coeliac disease (CD) is an autoimmune disease, characterised by a permanent sensitivity to gluten. It is being progressively recognised as a multisystemic disease, with multiple extraintestinal manifestations. Skin conditions (eg, dermatitis herpetiformis) are an example of its manifestations; however, its underlying mechanisms are still not well understood. This article presents three cases of uncommon skin conditions in patients with a history of CD. Two of them concern linear IgA bullous dermatosis and erythema nodosum, which have been described in the literature as having potential associations with CD, though only a few cases were reported. The third case corresponds to pityriasis lichenoides-a rare lymphoproliferative disorder of unknown aetiology-, which has no correlation with CD in the literature reviewed. The authors aim to draw attention to the possibility of CD as a potential predisposing factor for the occurrence of these skin diseases.

Febrile ulceronecrotic Mucha-Habermann disease (pityriasis lichenoides et varioliformis acuta fulminans) associated with parvovirus infection.

Febrile ulceronecrotic Mucha-Habermann disease is a rare fulminant variant of pityriasis lichenoides et varioliformis acuta, characterized by a rapidly progressive course with predominant ulceronecrotic lesions associated with fever and systemic manifestations. It carries a great morbidity and is potentially fatal. The exact pathogenesis is not clear, and it has been proposed to be the result of hypersensitivity reaction to an infection. We report a patient with febrile ulceronecrotic Mucha-Habermann disease in a 12-year-old boy in whom the condition was most likely precipitated by parvovirus infection, and he showed a favorable response to a combination of prednisolone with narrow band ultraviolet B (NB-UVB) phototherapy.

Pityriasis lichenoides et varioliformis acuta with numerous CD30(+) cells: a variant mimicking lymphomatoid papulosis and other cutaneous lymphomas. A clinicopathologic, immunohistochemical, and molecular biological study of 13 cases.

Pityriasis lichenoides comprises a clinicopathologic spectrum of cutaneous inflammatory disorders, with the 2 most common variants being pityriasis lichenoides et varioliformis acuta (PLEVA) and pityriasis lichenoides chronica. The aim of the study was to describe 13 cases of a unique PLEVA variant characterized in the conspicuous CD30 component and thus mimicking lymphomatoid papulosis (LyP), a condition currently classified in the spectrum of CD30 lymphoproliferative disorders. The cohort included 10 female and 3 male patients whose ages at diagnosis ranged from 7 to 89 years (mean 41 y; median 39 y). The clinical manifestation was that of PLEVA, with small erythematous macules quickly evolving into necrotic papules. No waxing and waning was seen on follow-up in any of the cases. Histopathologically, typical features of PLEVA were present, but an unusual finding was occurrence of a considerable number of CD30 small lymphocytes as detected immunohistochemically. Over half of the cases also displayed a large number of CD8 cells and showed coexpression of CD8 and CD30 in the intraepidermal and dermal component of the infiltrate. Of the 11 cases of PLEVA studied for T-cell receptor gene rearrangement, 6 evidenced a monoclonal T-cell population, and 5 were polyclonal. Parvovirus B19 (PVB19) DNA was identified in 4 of 10 cases investigated, and positive serology was observed for PVB19 in 2 patients, altogether suggesting that PVB19 is pathogenetically linked to PLEVA at least in a subset of cases. The presence of CD30 lymphocytes and CD8 lymphocytes would be consistent with an inflammatory antiviral response, as CD30, even atypically appearing lymphoid cells have been identified in some viral skin diseases. The main significance of the PLEVA variant is, however, its potential confusion with LyP or some cytotoxic lymphomas. Admittedly, the CD30 PLEVA variant described herein and LyP show considerable overlap if one takes into account all known variations of the 2 conditions recognized in recent years, thus suggesting that LyP and PLEVA may be much more biologically closely related entities than currently thought or can even occur on a clinicopathologic spectrum.

Lymphomatoid papulosis followed by pityriasis lichenoides: a common pathogenesis?

Pityriasis lichenoides (PL) and lymphomatoid papulosis (LyP) are uncommon idiopathic eruptions with overlapping clinical and histological features. Although current opinion indicates that PL and LyP are distinct and separate entities, molecular genetic evidence of T-cell clonality in both conditions suggests that an etiopathogenic relationship may exist. We report a patient who was diagnosed with LyP type B in 1985 followed by PL after 11 years. We hypothesize that LyP followed by PL in the same patient reflects differences in the host immune response to a common antigenic stimulus.

Pityriasis lichenoides chronica: stratification by molecular and phenotypic profile.

Pityriasis lichenoides (PL) has traditionally been classified as a benign papulosquamous disease. However, there is an increasing literature precedent that suggests that PL should instead be considered a form of cutaneous lymphoid dyscrasia. We prospectively encountered 46 patients with a diagnosis of PL and used immunohistochemical and multiplex polymerase chain reaction fragment size analysis to assess for phenotypic abnormalities and for T-cell clonal restriction, respectively. We categorized them into 2 groups based on the molecular profile, namely, those cases that showed a monoclonal and/or a restricted oligoclonal profile versus those cases that were polyclonal. Half of all the cases studied showed a monoclonal and/or an oligoclonal restricted T-cell repertoire. From a clinical perspective, 2 cases in this group manifested skin lesions compatible with mycosis fungoides (MF). All of the other cases demonstrated a persistent but nonprogressive clinical course characterized by periods of regression and recurrence. In any case in which there were multiple biopsies, the same T-cell dominant clonotypes, be it in the context of representing a true monoclonal and/or oligoclonal pattern, were implicated over time and at different biopsy sites, including 2 cases in which there was a subsequent evolution to MF. Substantial losses of CD7 and CD62L were seen in both monoclonal/oligoclonal and polyclonal cases of PL, although both values of percentage reduction were greater in the monoclonal/oligoclonal cases. A dominance of CD8 lymphocytes was seen in more than half of all the cases of PL and held to be reactive in nature, potentially directed against clonally restricted CD4 cells. CD4/CD25+ (Foxp3+) T cells averaged 24% in the polyclonal cases; it was 12% in the monoclonal variants of PL. We conclude that PL is a form of indolent cutaneous T-cell dyscrasia. The limited propensity for progression to MF may reflect internal countercheck mechanisms of controlling clonally restricted CD4+ T-cell proliferations via CD8 and CD4/CD25+ regulatory T cells.

Septic, CD-30 positive febrile ulceronecrotic pityriasis lichenoides et varioliformis acuta.

We report life-threatening febrile ulceronecrotic pityriasis lichenoides et varioliformis acuta in an 8-year-old girl. Hemorrhagic-crusted papules and plaques covered over 90% of the patient's body, leaving her susceptible to Pseudomonas aeruginosa and Staphylococcus epidermidis bacteremia as well as Candida parapsilosis fungemia. Sepsis delayed definitive treatment of the underlying cutaneous disease for 2 weeks. Combined therapy with methotrexate and cyclosporin caused remission of the process. Although immunohistochemistry revealed CD-30 positive cells, suggesting the diagnosis of lymphomatoid papulosis, the histopathology was most compatible with pityriasis lichenoides et varioliformis acuta. A partial loss of CD2 and CD5 in the predominant CD3 T-cell lymphocytes suggested a clonal proliferation. Elevated soluble interleukin-2 receptor levels reflected marked T-cell activation, and the downward trend of the levels during treatment coincided with clinical regression of this inflammatory dermatosis.

The role of cytotoxic skin-homing CD8+ lymphocytes in cutaneous cytotoxic T-cell lymphoma and pityriasis lichenoides.

BACKGROUND: Pityriasis lichenoides (PL) is a rare cutaneous lymphoproliferative disorder of unknown origin. Malignant transitions of PL have been described, but are very rare. We recently observed the fatal course of a 26-year-old patient who presented with a clinical picture resembling PL but had cytotoxic CD8+ T-cell lymphoma of the skin (CxCTL). This case prompted us to reinvestigate the role of cytotoxic T lymphocytes in PL and its relationship to antiviral immunity. METHODS: Skin biopsy specimens of 11 patients with PL and two biopsy specimens of CxCTL were included. In all, 5 biopsy specimens taken from healthy skin and 5 samples of varicella-zoster virus (VZV) skin lesions were analyzed for control purposes. The inflammatory infiltrate was characterized by immunohistochemistry using monoclonal antibodies against CD3, CD4, CD8, CD20, cutaneous lymphocyte-associated antigen (CLA), CCR4, CXCR3, Granzyme B, Tia-1, and MxA. Flow cytometry was used to analyze the expression of chemokine receptors on peripheral blood mononuclear cells in CxCTL. RESULTS: The CxCTL skin lesions were dominated by a dense infiltration of CD8+ cytotoxic lymphocytes with a skin-homing CLA+ CCR4+ phenotype. PL and VZV skin lesions were also characterized by a predominantly CD8+ T cellular infiltrate with strong expression of the cytotoxic molecules Granzyme B and Tia-1 and the skin-homing molecules CLA and CCR4. Coexpression analyses confirmed that skin CLA+ CD8+ cytotoxic T cells are present in CxCTL, VZV, and PL skin lesions. Strong lesional production of the antiviral protein MxA, which is specifically induced by type I interferons, could be found in all investigated disorders. The study was based on histologic, immunohistologic, and flow cytometric analyses in a limited number of patients, because of the rareness of the investigated diseases. CONCLUSION: Our results revealed a striking similarity between the immunohistologic picture of malignant CxCTL, benign PL, and VZV skin lesions. Strong expression of the antiviral protein MxA in all disorders supports the view that a common antiviral immune response pattern leads to aberrant skin recruitment of CLA+ CCR4+ cytotoxic T lymphocytes in PL and CxCTL.

Paraneoplastic pityriasis lichenoides in cutaneous lymphoma: case report and review of the literature on paraneoplastic reactions of the skin in lymphoma and leukaemia.

Paraneoplastic dermatoses are non-neoplastic skin disorders which occur in the context of an underlying malignant neoplasm. The classic paraneoplastic dermatoses are mostly associated with solid internal malignancies. They only rarely occur in the context of nodal or primary cutaneous lymphomas. Apart from these classic paraneoplastic dermatoses, there are additional skin disorders reported to occur in close association with haematological and lymphoproliferative disorders which can thus be regarded as paraneoplastic manifestations. We report for the first time two patients with pityriasis lichenoides et varioliformis acuta in association with mycosis fungoides. In addition, we review the literature on paraneoplastic dermatoses of the skin which have been described in patients with leukaemias and primary cutaneous lymphomas.

Febrile ulceronecrotic Mucha-Habermann disease with clonality: a cutaneous T-cell lymphoma entity?

Febrile ulceronecrotic Mucha-Habermann disease (FUMHD) is a severe variant of pityriasis lichenoides et varioliformis acuta (PLEVA). PLEVA patients only very rarely have systemic signs; the cutaneous lesions are usually asymptomatic, but may be pruritic and may heal with scarring. FUMHD often starts out as classic PLEVA, but goes on to develop widespread ulceronecrotic lesions and is associated with a high mortality rate. Whether Pityriasis lichenoides chronica (PLC) and PLEVA form a spectrum rather than single entities of clonal lymphoproliferative diseases has been discussed. Recently, it has been proposed that FUMHD, too, is a clonal lymphoproliferative disorder. Here, we report two cases of FUMHD with monoclonal T-cell population, as detected by Southern blot analysis. We propose that clonal FUMHD represents a cutaneous T-cell lymphoma entity.

Pityriasis lichenoides: a cytotoxic T-cell-mediated skin disorder. Evidence of human parvovirus B19 DNA in nine cases.

BACKGROUND: Pityriasis lichenoides et varioliformis acuta (PLEVA) and pityriasis lichenoides chronica (PLC) probably represent the polar ends of the same pathologic process, i.e. pityriasis lichenoides (PL), with intermediate forms in between. Previous studies have demonstrated that the inflammatory infiltrate in PLEVA is composed of cytotoxic suppressor T cells, whereas in PLC the helper/inducer T-cell population drives the immunological answer. Furthermore, monoclonal rearrangement of the T-cell receptor-gamma (TCR-gamma) genes was repeatedly found both in PLEVA and PLC. METHODS: Forty-one formalin-fixed, paraffin-embedded tissue specimens of 40 cases of PL were retrieved from the files of the authors. Immunophenotyping for cytotoxic granular proteins (Tia-1/GMP-17 and Granzyme B) and T-cell-related antigens (n = 41), TCR-gamma chain gene analysis (n = 30) and molecular investigations for parvovirus B19 (PVB19) DNA (n = 30) were performed. RESULTS: Overlapping immunophenotypes were observed in PLEVA and PLC. The dermal and epidermal T cells predominantly expressed CD2, CD3, CD8, and Tia-1 with a variable positivity for CD45RA, CD45RO, and Granzyme B. A monoclonal rearrangement pattern of the TCR-gamma genes was detected in three cases (10%). PVB19 DNA was found in nine cases (30%). T-cell monoclonality in conjunction with genomic PVB19 DNA was present in one case. CONCLUSIONS: Our results demonstrate that PL is a skin disorder mediated by the effector cytotoxic T-cell population. The identification of PVB19 DNA in nine cases may be interpreted ambiguously: PVB19 as a true pathogen or as an innocent bystander.

Febrile ulceronecrotic Mucha-Habermann disease: a case report and a review of the literature.

This report describes the case of a 76 year old man who suffered from febrile ulceronecrotic Mucha-Habermann disease (FUMHD). Despite this patient's typical clinical and histological findings, the fulminating course led to death. Polymerase chain reaction (PCR) analysis of the skin lesions showed that the infiltrating cells were monoclonal in origin and were from an aberrant clone. FUMHD is a very rare, febrile variant type of pityriasis lichenoides et varioliformis acuta, and is characterised by necrotic cutaneous ulcerations associated with high fever and systemic manifestations. Including this present case, only 18 cases of FUMHD have been reported. FUMHD can occur in both adults and children, although there are several differences between the manifestations of the disease in the two groups. One major difference is prognosis: all cases resulting in fatality are of the adult type, whereas no fatal cases have been reported among children. The aberrant clone detected by PCR may be responsible for host responses, resulting in the severe symptoms observed in this disorder.