ARTICLE
Auteur(s) : Chao‐Chun YANG, Julia Yu‐Yun LEE, WenChieh
CHEN
Department of Dermatology, College of Medicine, National Cheng
Kung University, 138 Sheng‐Li Road, Tainan, Taiwan
Reprints: W. Chen. Fax: (+ 886) 6 2004326 E‐mail:
wchenmail.ncku.edu.tw
Article accepted on 02\06\2003
Pityriasis lichenoides et varioliformis acuta (PLEVA), also
known as Mucha‐Habermann disease, is an uncommon, idiopathic,
acquired dermatosis characterized by erythematous, scaly papules
often accompanied by hemorrhagic and papulonecrotic lesions. A
febrile ulceronecrotic variant of PLEVA, also termed febrile
ulceronecrotic Mucha‐Habermann disease (FUMHD), first described by
Degos in 1966 [1], was more destructive and associated with high
fever and development of large coalescent skin necrosis. Here we
report a 14‐year‐old male case of this variant with unusual
extensive involvement of the intertriginous areas. We also review
the pediatric cases described in the literature.
Case report
A 14‐year‐old boy presented to our clinic with progressive,
extremely painful skin necrosis with oral and genital involvement.
About twenty days previously, he noticed some asymptomatic
scattered erythematous papules over bilateral wrists preceded by
low grade fever (37.7°C), sore throat, nasal congestion and
diarrhea. The rash progressed to trunk and thighs within three days
accompanied by persistent high fever. In the next week, the skin
lesions suddenly became worse and more extensive, evolving to
hemorrhagic bullae and pustules followed by ulceration and
confluent skin necrosis.
Physical examination showed numerous discrete, bean‐sized,
oval‐shaped, partially confluent necrotic papules and pustules with
thick hemorrhagic crusts distributed over neck, trunk, upper
extremities and thighs. There was extensive, nearly complete skin
necrosis with a foul odor and purulent discharge over flexural
sites such as axillae, neck, antecubital and inguinal areas (Fig. 1). Oral and
genital mucosal membranes were also involved with multiple
ulcerations. Laboratory examinations, including hemogram,
biochemistry studies, C‐reactive protein, anti‐streptolysin O,
urine analysis and chest X‐ray were all within normal limits.
Secondary infection with Staphylococcus aureus was
identified from his skin lesion.
.
Serological studies of Epstein‐Barr virus (EBV) capsule antigen
were as follows: IgG 1:320, IgA 1:40, IgM 1:10. Anti‐HIV antibody
was negative. Three skin biopsies taken from papular, pustular and
necrotic skin lesions, respectively, showed similar findings with
variable severity (Fig. 2). The epidermis
showed psoriasiform hyperplasia, hyperkeratosis with mounds of
parakeratosis and necrotic keratinocytes. Diffuse epidermal
necrosis with purulent crust and an infiltrate of lymphocytes in
the epidermis were present in the necrotic and pustular lesions. In
the dermis, there was a superficial and deep, perivascular,
moderately dense to patchy lichenoid lymphohistiocytic infiltrate
obscuring the dermo‐epidermal interface. There was no lymphocytic
atypia. Edema and focal hemorrhage was observed in the papillary
dermis. No evidence of vasculitis was present. Immunostaining
showed that the infiltrating lymphocytes were mostly CD3 +.
Approximately equal number of CD4 + and CD8 + lymphocytes
was observed in the epidermal and dermal infiltrate (Fig. 3). Staining with
CD30 was negative.
.
.
Oral erythromycin 2 g in four equal doses per day, together
with daily intravenous methylprednisolone of 80 mg was
initiated, with the latter soon tapered in steps to oral
prednisolone 30 mg per day within 7 days. Antibiotic
ointment was used topically. Most of the necrotic papules sloughed
off in one week and necrosis over intertriginous areas markedly
re‐epithelized and healed without scar formation. Oral ulceration
healed 9 days after hospitalization. Erythromycin at daily dose of
2 g was maintained for 2 months and no recurrence was
observed at 14‐month follow‐up.
Discussion
FUMHD is a severe form of PLEVA and about 22 cases have
been reported in the literature [2‐8]. It occurs more frequently in
children before 18 years of age, while PLEVA mainly occurs in
young adults in the second and third decades of life [2]. Males
predominated (male\female ∓ 8\3) in the 11 pediatric
cases under the age of eighteen (Table I) [9‐13]. No ethnic differences in the
incidence of PLEVA and FUMHD were known. The disease usually begins
as typical PLEVA, as seen in our patient, and rapidly evolves to
ulceronecrotic form with black oyster shell‐like hemorrhagic crusts
in 2 to 6 weeks [2]. Oral, genital and conjunctival
mucosas can be affected [14]. Associated symptoms include high
fever up to 40°C, malaise, myalgia, arthralgia, gastrointestinal
and central nervous system symptoms [15], interstitial pneumonitis
[10], lymphocytic myocarditis [16], and fatality [4, 16, 17].
Larger skin ulcerations can develop over the trunk and
intertriginous areas and often become secondarily infected [9, 15].
Noteworthy in our case was the extensive skin necrosis over
intertriginous areas with nearly complete detachment of epidermis
over axillae, inguinal areas, skin folds of the neck, abdominal
wall and antecubital areas. Secondary infection with
Staphylococcus aureus led to copious purulent discharge and
putrid smelling from ulcerations. The course of FUMHD usually lasts
several months with a succession of outbreaks until complete
healing or transformation to common PLEVA [2]. A comparison between
pediatric and adult cases showed the pediatric cases had shorter
time transforming to FUMHD, less mucosal involvement, more frequent
occurrence of vasculitis and favorable outcome (Table II). Our patient had rapid healing of
ulcerations within 1 month without residual scars, as opposed
to many previously reported cases displaying atrophic and
dyschromic residual scars [15].
Table I. Pediatric cases of febrile
ulceronecrotic Mucha‐Habermann disease (FUMHD) under the age of
eighteen
| Reference |
Age\Sex |
Distribution |
Possible etiology |
Systemic involvement |
Treatment |
Outcome |
| Kasamatsu et al. [2] |
4\M |
Unknown |
None |
None |
SC, DDS |
Cure |
| Luberti et al. [2] |
12\M |
Unknown |
None |
Arthritis, sepsis |
Antibiotics, SC, ACY |
Cure |
| Hsieh et al. [5] |
8\M |
Trunk, face, extremities, mucosa(‐‐) |
None |
None |
ACY, antibiotics, UVB |
Cure |
| Ricci et al. [6] |
10\F |
Trunk, extremities, mucosa(‐‐) |
EBV |
None |
ACY |
Cure |
| Burke et al. [7] |
12\F |
Trunk, extremities, mucosa(‐‐) |
None |
None |
SC |
Cure |
| Burke et al. [7] |
15\M |
Generalized, oral mucosa(+) |
None |
None |
SC, MET, KAN |
Cure |
| Auster et al. [8] |
7\F |
Generalized |
Adeno‐ virus |
Interstitial pneumonitis |
ERY, OXA, GM |
Cure |
López‐Estebaranz
et al. [9] |
18\M |
Trunk, face, extremities, mucosa(‐‐) |
None |
None |
SC, CIP, AMO, DOX, PUVA, MTX |
Cure |
Fink‐Puches
et al. [10] |
16\M |
Trunk, face, extremities, oral mucosa(+) |
None |
None |
SC, ERY, CIP, MTX |
Cure |
| Maekawa et al. [11] |
16\M |
Trunk, extremities |
None |
None |
ACY, CEF |
Cure |
| Our case |
14\M |
Trunk, extremities, intertriginous areas, mucosa(+) |
EBV |
None |
SC, ERY |
Cure |
Mucosa(+): mucosa involvement was present; Mucosa(‐): no mucosa
involvement; EBV: Epstein‐Barr virus; SC: systemic corticosteroid;
MET: methicillin; KAN: kanamycin; ERY: erythromycin; OXA:
oxacillin; GM: gentamycin; ACY: acyclovir; CIP: ciprofloxacin; AMO:
amoxicillin; DOX: doxycycline; MTX: methotrexate; DDS:
4,4‐diaminodiphenyl sulfone; CEF: cefotiam.
.
Table II. Comparison of pediatric and adult
cases of FUMHD
| Age group |
Patient number |
Age range (years) |
Male: female |
Progression* (range\mean) |
Mucosa (+ \ ‐‐ \NR)** |
Vasculitis (+ \ ‐‐ \NR)** |
Outcome |
Pediatric cases
( 18 year‐old) |
11 |
7 18 |
8:3 |
1 week 7 years\63.3weeks |
3\4\4 |
5\4\2 |
All cured |
Adult cases
(> 18 year‐old) |
12 |
21 82 |
8:4 |
5 days 35 days\ 17.4 days |
6\2\4 |
2\7\3 |
Four expired cases |
* Transformation time from onset of PLEVA to FUMHD
** + \ ‐‐ \NR: mucosa involved\mucosa not
involved\not recorded
.
The etiology of PLEVA or FUMHD remains unclear. Hypersensitive
reaction to some kind of infectious agent was suggested to be the
main cause by some authors [2]. Reactivated EBV infection in a
patient with PLEVA has been reported by Edwards et al. [18],
which was also reflected in our case by presenting high titers of
IgG and IgA with low IgM. Auster et al. reported positive
culture of adenovirus from the urine in a 7‐year‐old girl with
FUMHD and interstitial pneumonitis [10]. Using polymerase chain
reaction and in situ hybridization, Tsai et al.
detected cytomegalovirus infection in the skin biopsy specimen from
a 45‐year‐old male [19]. Immunological processes might contribute
to the pathogenesis of FUMHD. In a 21‐year‐old man with FUMHD
observed by Yanaba et al., a predominantly CD8
+ lymphocyte infiltrate around the dermis and into the
epidermis might suggest a cytotoxic attack of lymphocytes to
altered epidermal antigen perhaps induced by an unknown infectious
agent [7]. While CD8 + lymphocyte predominance was also observed in
PLEVA, CD4 + lymphocytes predominance was usually observed in
pityriasis lichenoides chronica [15]. In our case, both CD8 + and
CD4 + lymphocytes were detected, and their distribution and ratio
showed insignificant difference.
Other febrile conditions associated with large areas of skin
denuding and similar histopathology include Stevens‐Johnson
syndrome\toxic epidermal necrolysis (TEN) and graft‐versus‐host
disease (GVHD). The presence of Nikolski‘s sign and a relatively
scanty infiltrate in the dermis differentiates TEN from FUMHD. The
absence of a transplantation history ruled out the possibility of
GVHD. However, as a preferential accumulation of CD8 + cells
in the inflammatory infiltrate was observed in GVHD, TEN and FUMHD
[7], it seemed different etiologies might induce the same common
final pathogenetic pathway.
Several treatment modalities of FUMHD have been described and it‘s
difficult to evaluate the individual efficacy because of the small
number of patients and the combination therapy in most cases. Among
the 23 reported cases, including ours, systemic corticosteroid
was used in 15 cases, either initially or subsequently.
However, the benefit of prescribing corticosteroid seemed unclear,
especially for the elderly. All four reported fatal cases of FUMHD
received systemic corticosteroid [3, 4, 16, 17]. Tetracycline and
erythromycin, which yield favorable results in PLEVA probably due
to their anti‐inflammatory properties [15], were also commonly used
in cases of FUMHD, although the efficacy still remains to be better
defined. In our case, erythromycin was administered at the
beginning of clinical diagnosis of PLEVA, much earlier than the
further identification of bacterial superinfection. The initial
combination use of high dose corticosteroids seemed to rapidly
bring down the inflammatory component of the FUMHD, while the
prolonged treatment with erythromycin could maintain the
therapeutic effect. Methotrexate (7.5 to 25 mg weekly),
PUVA photochemotherapy, and 4,4‐diaminodiphenyl sulfone have also
been used to treat FUMHD [11, 20]. The effect of acyclovir is
questionable, since in pediatric cases, acyclovir was prescribed
because of the initial clinical impression of varicella [5, 6, 13],
but none of them was eventually proved to be associated with herpes
simplex or varicella‐zoster virus infection.
To summarize, we present a pediatric case of probably EBV‐related
FUMHD with extensive skin necrosis over intertriginous areas,
successfully treated with combination use of systemic
corticosteroid and erythromycin.
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