Are You Confident of the Diagnosis?
What you should be alert for in the history
The history of small or large plaque parapsoriasis (SPP or LPP) is remarkable for its chronic indolent course (sometimes for decades); the lack of symptoms except for possible mild pruritus; and the tendency to improve and even regress fully during summer or exposure to sunlight. As parapsoriasis and specifically LPP is related to mycosis fungoides (MF), ask the patient about a personal or family history of lymphoma. Patients with parapsoriasis may rarely have a history of pityriasis lichenoides.
Characteristic findings on physical examination
On physical examination both SPP and LPP are characterized by patches (or sometimes flat plaques) rather than infiltrated plaques, consistent with the fact that the French term plaque equates to the English term patch. The lesions are variably erythematous and located on sun-protected areas. In dark-skinned patients, the lesions may be hyperpigmented or hypopigmented.
SPP is characterized by monomorphic eruptions composed of round-oval, regularly shaped patches covered by fine scale, measuring 2-6 cm in diameter. The lesions may have a slight atrophic surface. Poikilodermatous changes are rare. The patches are erythematous, sometimes exhibiting salmon or yellowish-red color. In the digitate variant the lesions are characterized by elongated, finger-like patches that may measure anywhere from less than 6 cm to 10 cm or greater along their long axis (Figure 1).
Lesions of SPP are usually located bilaterally, typically on the upper trunk. However, it often involves also the limbs, preferentially the inner aspects of the upper limbs, lower trunk, groin and inner thighs. Lesions can be widespread or more limited in their distribution. The lesions of the digitate variant are typically oriented along the cleavage lines and usually located symmetrically on the sides of the torso.
The patches of LPP resemble SPP, but they are larger and less monomorphic. Most lesions are larger than 6 cm and are located on the trunk and limbs. Specifically, LPP is found on the inner aspects of the upper limbs, lower trunk including buttocks, inframammary areas, and thighs (Figure 2). It is composed of round-oval and/ or irregularly shaped scaly patches, usually with an atrophic surface. In rare cases, the lesions exhibit the clinical triad of poikiloderma vasculare atrophicans; ie, atrophy, hyper- and hypopigmentation, and telangiectasia.
As in the case in SPP, the lesions are variably erythematous, ranging from red-brown to brighter red. In skin of color, they may be hyperpigmented or hypopigmented. Hypopigmented patches can also be seen in children. Since LPP can progress to overt MF, look carefully for the possible presence of lesions suggestive of MF (patches with unusual configuration; more infiltrated plaques, a majority of lesions in double-covered areas), and for the presence of any enlarged lymph node.
“Retiform parapsoriasis” is a variant of LPP. It is typified by widespread ill-defined patches in a net-like pattern.
Lesions of SPP and LPP can be observed in the same patient at the same time. Therefore, look for the possible presence of these two types of lesions in any patient with clinical features of parapsoriasis.
Expected results of diagnostic studies
Histopathological examination (preferably 6 mm in diameter) is the next step in the diagnostic work-up of SPP or LPP. With the exception of emollients, it is essential to stop all topical treatments, especially steroids, at least 2 weeks before biopsy, or else the histopathologic features can be suppressed.
In patients with SPP with uniform lesions, it is usually enough to obtain a single biopsy from a representative lesion. In patients with LPP, especially in those exhibiting size and/or shape variation, it is advised to obtain biopsies from multiple sites to rule out the possibility of MF. Certainly, the presence of any poikilodermatous patch in such a context is highly suspicious for MF and should be biopsied. Also, patches with unusual configuration (arciform or kidney-shaped lesion) should also raise the suspicion for MF and should be biopsied.
The histopathological findings of SPP and LPP are characterized by nonspecific changes with occasional findings that may overlap with patch-stage MF. There is a lymphocytic infiltrate in the superficial dermis. The overlying epidermis demonstrates focal spongiosis and/or psoriasiform acanthosis. Sometimes focal exocytosis of small lymphocytes with or without spongiosis can be seen, but the overall findings failed to meet the minimum histopathological criteria for MF. The infiltrate is composed predominantly of CD4+ T cells. Clonal rearrangement of T cell receptor done by polymerase chain reaction (PCR) is found in lesional skin in variable percentages of both types of parapsoriaisis, although more frequently in LPP.
There are no published recommendations for immunohistochemical and genotypic analysis in parapsoriasis. Currently, most authors maintain that the diagnosis of parapsoriasis is based merely on the correlation between the clinical and histopathological findings. There is no need for any blood or radiologic test in cases with SPP or LPP, although there are no published guidelines.
Usually the clinical diagnosis of SPP is straightforward. The main differential diagnosis is SPP-like MF. According to one large study, 27% of patients with SPP had histopathological findings of early MF. However, whether such patients should be diagnosed as patch- stage MF is still controversial, since the prognostic implication of such cases is unknown.
In patients presenting with a short history of eruption (up to several weeks), pityriasis rosea (PR) may be included in the differential diagnosis. However, SPP is rarely so widespread as PR. Also, the herald patch and the collarette scales covering the lesions, both of which are characteristic of PR, are lacking in SPP. In patients presenting with a short history (up to several months) of eruption, secondary syphilis may be included in the differential diagnosis. Always check the peripheral lymph nodes which are characteristically enlarged in secondary syphilis.
The main and almost the sole differential diagnosis of LPP is MF. In fact, on a clinical ground only it is impossible to differentiate between patch-stage MF and LPP. The final diagnosis is based primarily on the histopathogical findings, namely whether diagnostic for MF or not fulfilling the criteria for this malignancy. Cases exhibiting clinical features of LPP but histopathological findings of MF should be diagnosed as patch-stage MF and not as LPP.
However, it should be remembered that there are no universally accepted minimum criteria for the diagnosis of early MF. Furthermore, definite histopathologic diagnosis by hematoxylin-eosin staining alone may be difficult to make in early MF. The International Society of Cutaneous Lymphoma (ISCL) proposed a diagnostic algorithm for early MF. This incorporates clinical, histopathological, immunohistochemical, and genotypic features. At a total of at least 4 points is necessary for the diagnosis of MF. Therefore, in cases with LPP showing histopathologic features suggestive but not diagnostic to MF, it is advised to order immunohistochemical stainings and TCR gamma gene rearrangement analysis.
Macular granuloma annulare in “bathing trunk” distribution can be misdiagnosed clinically as LPP. However, the fine scales and the atrophic surface that are characteristic of LPP are lacking in granuloma annulare.
Finally, lymphomatoid drug eruption is mentioned in some textbooks as a possible simulator of SPP and LPP. However, such cases are extremely rare. There is one case report on ACE inhibitor- induced digitate dermatosis of 3 years’ duration. The eruption cleared a few months after discontinuation of the drug. Therefore, despite its rarity, it is advised to take a meticulous drug history in patients with parapsoriasis, with special emphasis of the drugs reported in the literature to induce lymphomatoid drug reactions (ACE inhibitors, anticonvulsants, calcium channel blockers, antidepressants, lipid lowering agents, antipsychotics, antihistamines, beta blockers)
Who is at Risk for Developing this Disease?
There is a definite male predominance. Parapsoriasis can affect any age group, although it is rare among children. The peak incidence is the fifth decade. There are no known precipitating factors, such as infections. At present there are no means to predict which PP will progress to MF. Although the prognostic value of a T-cell clone remains controversial, the results of a recent study suggest that the presence of a cutaneous T-cell clone in patients with PP is a predictor of progression to MF.
What is the Cause of the Disease?
Both the etiology and the pathogenesis of parapsoriasis are unknown.
Parapsoriasis is currently viewed as a form of clonal dermatitis, given the detection of T-cell clonality in a fraction of patients with either SPP or LPP. Both types probably represent different stages in a continuum of cutaneous lymphoproliferative disorders. Progression of SPP to biopsy-proven plaques and tumors of MF has been documented in exceedingly rare cases. Therefore, despite the occasional detection of histopathological features of MF in cases with clinical features of SPP, it is still controversial whether they actually represent SPP-like MF or just simulant of MF.
These findings can be detected already at the first evaluation of the patient, or later in the course of the years (in one retrospective study, up to 10% of SPP patients under follow-up). It has been suggested that SPP is an abortive lymphoma in which the neoplastic cell clone never overcomes the host control mechanisms and cannot expand. Currently most authors regard SPP as a dermatitis having little if any potential to evolve to overt MF.
In contrast, long-term follow-up of patients with LPP has documented the development of overt MF in 7.5%-14% of cases. These findings, together with the detection of histopathological findings of MF in a significant percentage of patients with clinical features of LPP (either at the time of the first evaluation or later in the course of the years) indicate that a fraction of cases with LPP actually represents a patch-stage of MF. Controversy still exists as to whether all cases of LPP should be considered as early-stage MF, or only those fulfilling the criteria for the definite diagnosis of MF. In the author’s opinion, LPP lacking the histopathologic findings of MF, or failing to meet the minimum criteria proposed by the ISCL for early diagnosis of MF, should be viewed as a precursor of MF.
Systemic Implications and Complications
SPP or LPP is not associated with any systemic illness. With the exception of the potential risk for LPP to become MF, there are no systemic features of SPP or LPP. Recently, Danish patients with parapsoriasis were found to have a significantly increased risk for subsequent cancers, most notably non Hodgkin’s lymphoma and other haematological malignancies.
Treatment options are summarized in Table I.
|Medical Treatment||Physical Modalities|
|Topical bexarotene||Sun bathingPUVATopical PUVABBUVBUVA+ UVBtargeted phototherapyExcimer laser|
Optimal Therapeutic Approach for this Disease
There is no curative treatment for SPP and LPP. Long periods of complete remission are usually not achieved following discontinuation of treatment. The therapeutic approaches are based on case series and experts’ opinions.
SPP has little if any potential to evolve to overt MF. Therefore the short -term benefit of any treatment should be balanced carefully against the potential for side effects. Taken together, noninterventional strategy is a legitimate first-line approach.
Determine the extent of the eruption, and what effect it is having on patient’s quality of life. In patients with relatively few lesions who require treatment, topical potent to superpotent steroids (e.g,. clobetasol propionate 0.05%) are the first-line treatment. The steroid should be applied every night until disappearance of lesions (usually within 2-3 weeks) and then either to discontinue the treatment or to reduce the frequency of application to once or twice a week as a maintenance therapy.
Narrow band ultraviolet B (NBUVB) is a second-line treatment in such cases. The vast majority of patients will achieve complete response. In one study, all patients achieved complete response after a mean number of 33 exposures. Maintenance therapy is usually not justified. For those with the very localized form of SPP, targeted phototherapy or excimer laser are reasonable options. Bexarotene 1% gel has been found to be beneficial in a small series of patients with overall response of 63%. All patients experienced skin irritation.
In patients with a widespread disease who require therapy, NBUVB is the first-line treatment. Except for psoralen plus UVA (PUVA), other phototherapeutic alternatives appearing in the table are reasonable options. Maintenance therapy can be considered. The tendency of SPP to relapse suggests that patients may require high numbers of UV exposures during their lifetime to keep the disease in remission. Therefore, because of safety considerations, PUVA usually should be reserved for patients who failed other phototherapeutic approaches. In general, sunlight exposure during the safe hours with or without topical steroids is a reasonable alternative to phototherapy in cases with SPP.
Most of the authors believe that patients with LPP that does not meet the criteria for early MF should be treated in order to induce meaningful remission. However, currently there is no evidence that treatment prevents the progression to MF. In one study, there was no significant difference between UV-treated or nontreated patients with respect to the development of MF in either SPP or LPP.
Although the therapeutic options for both types of parapsoriasis are similar, PUVA is given more widely for patients with LPP, due to the nature of the disease. Sunlight exposure during the safe hours with or without topical steroids is a reasonable alternative to phototherapy in cases with LPP with relatively few lesions. LPP that is actually a manifestation of patch-stage MF should be treated accordingly (see relevant chapter).
Explain that SPP and LPP are chronic conditions with indolent course, often with periods of exacerbation and regression. Explain the factors that may affect the appearance of the lesions: sun exposure usually leads to fading of the lesions, while showering with hot water sometimes renders the lesions more prominent, due to dilatation of blood vessels. Explain that in general there is no curative treatment for parapsoriasis. Stress that after discontinuation of treatment, both types usually relapse within months, but sometimes after longer periods.
Make sure that the patient understands that SPP is an inflammatory condition. Reassure the patient that the risk of developing a cutaneous lymphoma with potential for life-threatening outcome is practically nil. Tell the patient that the risk of any treatment should be balanced carefully against the potential side effects, and overtreatment should be avoided. Stress that there is no evidence that treatment may affect the progression to MF. Taken together, explain that therapy is not mandatory.
Explain that LPP is considered as a pre-lymphomatous skin condition. Explain that despite the lack of evidence with respect to the benefit of treatment in preventing progression to MF, all leading authorities recommend treating the eruption. It is important to emphasize the need for periodical follow-up. Explain that repeated biopsies are to be expected in the future, to rule out the development of MF. Reassure the patient that should MF develop, the prognosis for early-stage MF, and specifically patch-stage, is favorable. In case the patient is diagnosed as having patch-stage MF, see the chapter devoted to cutaneous T-cell lymphoma.
Unusual Clinical Scenarios to Consider in Patient Management
In patients with severe sun-damaged skin with or without a history of nonmelanoma skin cancer, the combination of NBUVB and acitretin should be considered. In patients with widespread LPP who are at high risk to develop melanoma, caution should be exercised with phototherapy, especially with PUVA. In general, avoid maintenance treatment with phototherapy. Topical nitrogen mustard is a reasonable alternative option in such cases.
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