Dermatology Online Journal

Diffuse cutaneous mastocytosis: Report of a severe case with fatal outcome
Maryam Ghiasi MD¹, Alireza Ghanadan MD², Shab Bu Jesri MD¹, Soheyla Sotudeh MD³, Asghar Ramyar MD⁴
Dermatology Online Journal 17 (3): 7

1. Tehran University of Medical Sciences, Department of Dermatology, Razi Hospital, Tehran, Iran
2. Tehran University of Medical Sciences, Department of Pathology, Razi Hospital, Tehran, Iran
3. Tehran University of Medical Sciences, Children’s Medical Center, Tehran, Iran
4. Tehran University of Medical Sciences, Department of Hematology and Oncology, Children’s Medical Center, Tehran, Iran

---

Abstract

Diffuse cutaneous mastocytosis (DCM) is a rare variant of mastocytosis. We describe a case of DCM with a very severe presentation at birth and fatal outcome.

---

Introduction

Mastocytosis is a disorder of mast cell proliferation that occurs in both cutaneous and systemic forms. The most frequent site of organ involvement in patients with any form of mastocytosis is the skin, in which a variety of clinical manifestations have been described. Cutaneous lesions include urticaria pigmentosa, mastocytoma, diffuse cutaneous mastocytosis (DCM), and telangiectasia macularis eruptive perstans [1].

Case report

Figure 1	Figure 2
Figure 1. Diffuse thickening and erythema of the skin Figure 2. Multiple nodules on the face

A three-day-old female neonate presented with a diffuse skin eruption, present since birth. The whole skin was erythematous and very severely thickened. It had a leathery appearance and doughy texture with exaggeration of skin markings. The palms and soles were involved. There were multiple scattered nodules, especially on the face and scalp. Several intact and eroded hemorrhagic bullae (scattered on the back, occiput, and soles) were identified. Darier sign was positive. There was no family history of any significant skin disorder.

Figure 3	Figure 4
Figure 3. Diffuse infiltration of mast cells through the dermis (H&E, x10) Figure 4. Giemsa staining reveals metachromatic granules within mast cells (Giemsa, x100)

Skin biopsy was performed. Confluent infiltration of mast cells was seen in the entire dermis; these exhibited cytoplasmic granules that stained metachromatically with Giemsa. The diagnosis of DCM was made on the basis of the clinical presentation and histological findings. Complete blood count, peripheral blood smear, and chemistry profile were normal. Total tryptase level was 6 ng/ml. There was no lymphadenopathy, but hepatosplenomegaly was evident by ultrasonography. Bone marrow biopsy was performed by a pediatric hematologist and the result was normal. H1 and H2 antagonists were prescribed and parents received counseling about the avoidance of mast cell degranulators. Although bone marrow biopsy was normal, we could not rule out the possibility of systemic disease especially hepatic involvement. We decided to follow up the infant carefully regarding internal organ involvement. Unfortunately, the baby died at the age of one month at home and the exact cause of death was not determined.

Discussion

Mastocytosis is a disorder of mast cell proliferation in body tissues. It usually presents in the skin, but may affect other tissues, especially the bone marrow and gastrointestinal tract. Disease involvement may be primarily cutaneous, as seen most commonly in the pediatric population, or systemic, as is more typical of adult-onset disease [2].

Adult-onset mastocytosis and those cases with associated hematological diseases usually express an activating mutation of the growth factor receptor c-kit. Most cases of childhood-onset mastocytosis, that generally remits, had been thought to lack this mutation [3]. However, Bodemer et al [4] recently presented a large series of childhood cases of mastocytosis in which there was a high rate of somatic mutation leading to c-KIT activation in this pediatric population.

Cutaneous mastosytosis can be divided into 4 different clinical variants: 1) urticaria pigmentosa, 2) solitary mastocytoma, 3) DCM, and 4) telangiectasia macularis eruptive perstans [3]. Frequency of cutaneous mastocytosis clinical presentation in children differs in the literature. Torrelo et al, Azana et al, and Stein found urticaria pigmentosa to be the most common form (58.4-90% of cases) followed by mastocytoma (10-40% of cases), while Hannaford and Rogers reported 51 percent of cases with mastocytoma [5, 6, 7, 8].

Cutaneous mastocytosis may be associated with both local and systemic symptoms, including flushing, blistering, pruritus, shortness of breath, asthma exacerbation, hypotension, and gastrointestinal upset, including acid reflux, peptic ulcer, and diarrhea. These symptoms occur because of the degranulation of mast cells with the release of multiple mediators. The most significant of these mediators is histamine, which can cause local reaction, as well as systemic response [9]. Tryptase is another mediator of mast cells. In general, total tryptase levels are greater than 20 ng/ml in patients with systemic mastocytosis [10].

Differences between adults and children with cutaneous mastocytosis consist not only in frequency of systemic alterations but also mostly in prognosis [3]. The majority of pediatric cases of cutaneous mastocytosis show a good prognosis with gradual resolution of both symptoms and skin lesions [9]. In children, systemic alterations like hematological abnormalities, bone marrow disorder, skeletal lesions, gastrointestinal involvement, and hepatosplenomegaly are rare and, when present, are brief and in most cases undergo spontaneous resolution. In adults, in contrast, these alterations usually have a progressive and chronic course, with increased morbidity and mortality [3].

Diffuse cutaneous mastocytosis is a rare variant of cutaneous mastocytosis. It occurs predominantly in infants. The skin is infiltrated by mast cells in a generalized pattern leaving a thickened, doughy appearance that accentuates skin folds. In the more severe form, blistering may be present. There are varying degrees of erythroderma and pruritus. The combined result of both the infiltration of mast cells and their degranulation products produces edema and a typical leather-grain skin appearance. There may also be nodules or plaques that develop, representing areas of greater mast cell infiltration [9]. Patients with DCM are at a higher risk than other forms of cutaneous mastocytosis and they are more likely to suffer severe complications including hypotension, anaphylaxis, severe diarrhea, and gastrointestinal manifestations because of the much higher concentration of mast cell mediators [1, 7, 9]. However, like other forms of cutaneous mastocytosis, symptom severity will lessen over time and DCM usually resolves spontaneously between the age of 15 months and 5 years [1]. Overall, DCM has a good prognosis; in the follow-up of 18 patients with DCM in the literature there were only three fatal cases [3]. However because of extensive involvement, these patients should be followed closely.

Our case is remarkable for its severe presentation at birth and its fatal outcome. To our knowledge, most cases of DCM present in the first few months of life, but presentation at the time of birth is very rare.

References

1. Soter NA. The skin in mastocytosis. J Invest Derm 1991 Mar; 96(3 suppl): 32S-38S; discussion 38S-39S, 60S-65S. Review. [PubMed]

2. Duckworth AK, Bhatti A, Barnes C. Diffuse cutaneous mastocytosis in fraternal twins. Int J Dermatol 2009 Feb; 48(2): 170-172. [PubMed]

3. Kiszewski AE, Duran-Mckinster C, Orozco-Covarrubias L, et al. Cutaneous mastocytosis in children: a clinical analysis of 71 cases. J Eur Acad Dermatol Venereol 2004 May; 18(3): 285-290. [PubMed]

4. Bodemer C, Hermine O, Palmérini F et al. (2010) Pediatric mastocytosis is a clonal disease associated with D816V and other activating c-KIT mutations. J Invest Dermatol 130:804–15. [PubMed]

5. Torrelo FA, Navarro CL, Escribano ML, Zambrano AZ. Estudios clinicos y de laboratorio: diagnostico, tratamiento y calasificacion de la mastocitosis pediatrica. Estudio de 172 casos. Actas Dermosif 1998; 89: 461-476.

6. Azana JM, Torrelo A, Mediero IG, Zambrano A. Urticaria pigmentosa: a review of 67 pediatric cases. Periatr Dermatol 1994 Jun; 11(2): 102-106. [PubMed]

7. Stein DH. Mastocytosis: a review. Pediatr Dermatol 1986 Nov; 3(5): 365-375. [PubMed]

8. Hannaford R, Rogers M. Presentation of cutaneous mastocytosis in 173 children. Australas J Dermatol 2001 Feb; 42(1): 15-21. [PubMed]

9. Briley LD, Phillips CM. Cutaneous mastocytosis: a review focusing on the pediatric population. Clin Pediatr 2008 Oct; 47(8): 757-761. [PubMed]

10. Schwartz B.Diagnostic value of tryptase in anaphylaxis and mastocytosis. Immunol Allergy Clin North Am 2006 Aug; 26(3): 451-463. [PubMed]

© 2011 Dermatology Online Journal