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Clinical Updates

Yoshiki Miyachi, MD, PhD

Skin Diseases First Described by Japanese Dermatologists. Part 1: Papuloerythroderma of Ofuji

Yoshiki Miyachi

Wednesday, January 12, 2011

Papuloerythroderma of Ofuji (PE) was first described as a novel clinical entity by Professor Shigeo Ofuji, Kyoto University, Japan, in 1984 as a peculiar form of erythroderma quite different from ordinary exfoliative dermatitis.1 Initial skin lesions of PE comprise solid lichenoid papules that demonstrate a cobblestone-like appearance and develop into erythroderma. Another important characteristic feature of PE is the so-called "deck-chair sign", sparing skin folds and creases. As one of the co-authors of the first report of PE, I witnessed how and why Ofuji considered these skin manifestations, which did not correspond to any of the known dermatoses, to be specific. As PE is still underdiagnosed and poorly recognized in non-Asian countries, this article reviews the clinical features and possible pathoetiology of PE in order to improve the world-wide recognition of PE.

Why Is It Named PE?

Ofuji noticed several atypical erythroderma cases that were considered different from ordinary exfoliative erythroderma because they began with solid papules that then developed into erythroderma-like lesions. He documented these fairly characteristic cases in Japanese journals pre-1984 and confirmed that nobody had observed or described similar cases before. He then reported four cases as a possible new clinical entity under the name of PE in 1984.1

PE starts with the appearance of flat-topped papules that spread over the body, resulting in a cobblestone-like assembly and confluence which is not observed in idiopathic exfoliative dermatitis (Figure 1). The body is finally and extensively involved, except for the face, forming erythroderma-like lesions. At this point, several other skin diseases, such as sarcoidosis, lichen planus and lymphoma, should be excluded. However, differential diagnosis is not difficult because histopathology always reveals non-specific perivascular infiltration of lymphocytes and histiocytes into the upper dermis, with occasional tissue eosinophilia (Figure 2).

Figure 1. Cobblestone-like assembly of solid papules as an initial lesion of PE.

 

Figure 2. Histopathology of PE. Non-specific perivascular infiltration of lymphocytes and histiocytes is seen in the upper dermis with tissue eosinophilia (hematoxylin and eosin stain).

 

In addition, the axillae, inguinal regions, cubital fossae and the big furrows on the abdomen are clearly spared from the lesions - later termed the "deck-chair sign" (Figure 3).2 The mechanism by which the "deck-chair sign" appears still remains unclear. Possible involvement of ultraviolet light or contact dermatitis seems unlikely. My simple speculation is that some "occlusive dressing effect" of topical corticosteroids may have something to do with this phenomenon because, in skin folds, topical corticosteroids stay longer, penetrate deeper and work better, leading to a stronger clinical effect in interrupting new formation of the rash.

Figure 3. The body is extensively involved with an erythroderma-like appearance. The characteristic sparing of the skin folds is called the "deck-chair sign".

 

 

Systematic Review of The Worldwide Literature

Torchia et al. published an extensive systematic review of the worldwide literature on PE in 2010.3 They reviewed 170 cases of PE and concluded that PE represents a rather monomorphous entity, both clinically and histologically, with the remarkable exception of cutaneous T-cell lymphoma (CTCL).

They suggested the following etiological classification of PE as a result of their analysis:

  1. Primary (idiopathic) PE.
  2. Symptomatic PE secondary to atopic dermatitis, drugs, infections and malignancies.
  3. PE-like CTCL.
  4. Pseudo-PE with the "deck chair sign" in the absence of papules.

Finally, they proposed diagnostic criteria for PE, as shown in Table 1. Using these criteria, we can reach an exact diagnosis of PE, or make a differential diagnosis of secondary PE, PE-like CTCL or pseudo-PE. 

 Table 1. Redrawn from Torchia D et al.3


Necessary Criteria

  1. Erythroderma-like eruption formed by the coalescence of flat-topped, red-to-brown papules with a cobblestone-like appearance
  2. Sparing of skin folds and creases (deck-chair sign)
  3. Itch
  4. Histopathological exclusion of CTCL (and other skin diseases)
  5. Workup and follow-up to exclude a causative link with malignancies, infections, drugs and atopy

Additional Minor Criteria

  • Age greater than 55 years
  • Male gender
  • Peripheral and/or tissue eosinophilia
  • Increased serum IgE
  • Peripheral lymphopenia

Criteria 1-5: primary (idiopathic) papuloerythroderma (Ofuji).
Criteria 1-4: secondary (symptomatic) papuloerythroderma.
Criteria 1,2,3,5: papuloerythroderma-like CTCL.

What To Do When You Encounter A Patient With PE

In such circumstances, one has to exclude the possibility of CTCL, as well as any complicated internal malignancy. Since the synchronous or diachronical coexistence of PE and malignancy was reported in 21.76% of patients, which was much higher than expected, even in such elderly patients, patients should be checked for both solid and hematological malignancies; however, in this study, the majority of PE patients were generally healthy except for skin eruptions.3

Recent reports have indicated that drugs might be causative agents for PE, suggesting that drug-reactive Th2 cells play an important role in its pathogenesis.4 A review of the literature revealed that various drugs can cause drug-induced PE following a mean administration period of 2 years and 3 months.3,4 Despite the chronic type of eruptions, provocation tests but not patch tests were positive in all patients. The authors demonstrated that Th2 cells were a propagating population in drug-induced PE, which is consistent with both the peripheral and tissue eosinophilia seen in most cases.

As for the treatment for PE, there is no evidence-based standard therapy. After excluding underlying causes of PE, mild symptomatic therapies, such as antihistamines for pruritus and topical corticosteroids with or without phototherapy, appear to be reasonable, as most patients are usually otherwise healthy and PE lesions improve slowly after several years.

Conclusions

Although PE is a rare condition and not well-recognized by non-Asian dermatologists, it is very easy to make a diagnosis once you notice certain clinical features. More studies, however, are required to answer the still unresolved questions of why PE is found mainly in men, and rarely in women, and why the 'deck chair sign' occurs.

The following points serve as a take-home message for dermatologists:

  • PE is different from exfoliative erythroderma because it starts as solid lichenoid papules that develop into an erythroderma-like appearance.
  • The "deck-chair sign", eosinophilia and increased IgE are of great help for correct diagnosis.
  • If you find a patient with PE, check carefully for complicated internal malignancies and drugs as possible causative agents.


References

  1. Ofuji S, Furukawa F, Miyachi Y, et al. Papuloerythroderma. Dermatologica. 1984;169:125-130.
  2. Farthing CF, Staughton RC, Harper JI, et al. Papuloerythroderma-a further case with the 'deck chair sign'. Dermatologica. 1986;172:65-66.
  3. Torchia D, Miteva M, Hu S, et al. Papuloerythroderma 2009: two new cases and systematic review of the worldwide literature 25 years after its identification by Ofuji et al. Dermatology. 2010;220:311-320.
  4. Sugita K, Kabashima K, Nakamura M, et al. Drug-induced papuloerythroderma: analysis of T cell populations and a literature review. Acta Derm Venereol. 2009;89:618-622.
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