DermDx: Infant With Patch of “Raw Skin”

Case #1: Aplasia cutis congenitAplasia cutis congenita (ACC) is a rare congenital condition present at birth characterized by absence of the skin.1 The first description of the condition affecting the extremities dates from 1767, and the first report of skull...

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Case #1: Aplasia cutis congenit

Aplasia cutis congenita (ACC) is a rare congenital condition present at birth characterized by absence of the skin.¹ The first description of the condition affecting the extremities dates from 1767, and the first report of skull involvement was from 1826.² Roughly 80% of cases involve the skin overlying the skull, and 15% to 30% of those cases feature deeper involvement of underlying structures such as the epicranial aponeurosis, the skull itself, or even the dura or cerebrovasculature.³

The incidence of ACC is estimated to be about 3 in 10,000 live births.⁴ However, given the heterogeneity of the disease in terms of severity, the true incidence is likely higher as milder cases are thought to be underreported.⁵ ACC can be an isolated finding, or it can coexist with other syndromic features, such as in Trisomy 13, Adams-Oliver syndrome, Johanson-Blizzard syndrome, and Golt syndrome, among others.^3,6 

The etiology of ACC is thought to be multifactorial. When ACC exists as part of a syndrome, certain genes have been implicated, such as in Adams-Oliver Syndrome.6 For isolated ACC, genetic influence is still likely as both autosomal dominant and recessive inheritance patterns have been described.⁷ Sporadic ACC has several proposed etiologies, mostly related to perinatal insults, including intrauterine infections, vascular insufficiency or placental infarcts, amniotic membrane adhesions, ectodermal dysplasia, neural tube defects, or teratogenic effects.⁸ Several case series have implicated methimazole exposure during pregnancy to ACC, and other drugs such as carbamazepine, misoprostol, and valproic acid also have proposed associations.⁹ Outside of known family history or genetic syndromes, along with exposure to previously discussed teratogens, there are few established risk factors for ACC. However, it has been noted to be more common in females than in males.⁸

Diagnosis of ACC can be difficult given its highly varied presentation. The defect can range from large with associated skull deformities to small atrophic scars present on the extremities.⁷ The morphology of the lesions is also highly variable, with reports ranging from multiple bullous ulcers arranged along blaschkos lines to membranous corporal stellate lesions.^7,10 The hair collar sign (long, dark hair encircling the lesion), midline lesions, and nodular features can be important clues to suggest deeper involvement.⁴ Histologic analysis reveals the absence of structures such as sweat and sebaceous glands, hair follicles, and collagen in the dermis.⁸ The Freiden classification is commonly used to help specify the location of the lesions and any associated syndromes or features.¹¹ 

The diagnosis of ACC is based primarily on clinical features. For larger defects, there is a possibility of making a prenatal diagnosis via ultrasound, although the vast majority of cases are diagnosed postnatally.^5,8 The differential diagnosis includes: neonatal herpes simplex, other developmental defects including atretic cephalocele or heterotopic brain or glial tissues, bullous impetigo, or trauma from forceps, vacuum extractors, or even scalp electrodes.⁷ One must exclude epidermolysis bullosa, a group of genetic bullous disorders characterized by extremely fragile skin.⁷ After diagnosis of ACC, it is important to evaluate for other associated anomalies that could have important management or diagnostic implications.⁷ For example, Adams-Oliver syndrome should be suspected with ACC associated with malformations of the limbs or digits or in a patient with a strong family history.⁷ A patient with coexisting nevus sebaceous or a large pigmented nevi should be evaluated for SCALP syndrome, which would mandate an MRI.¹² As mentioned, large scalp defects or those with concerning features such as the hair collar sign should also raise the possibility of skull and dural involvement.^7,8 

There is no treatment consensus for ACC, but the general goal should be complete and stable coverage of the defect to avoid infectious complications.⁷ The general health of the infant, as well as the size and location of the lesion, should all be taken into consideration when formulating a treatment plan.⁷ For smaller lesions, conservative management with simple dressing changes can be adequate.⁷ Treatment options for more significant lesions range from topical bacitracin, betadine, silver sulfadiazine, or even synthetic biologic skin substitutes.⁷ Larger defects may require surgical interventions, including skin grafting, excision and closure, and tissue expansion.⁷ Common complications include infections, desiccation with bleeding, and delayed healing.⁷ For many cases, atrophic plaques, prominent scars and cicatricial alopecia are common after healing of the defect.⁷ 

The patient described in this case was diagnosed with ACC based on history and clinical examination. A thorough evaluation revealed no associated abnormalities to suggest syndromic ACC. Conservative management with Vaseline and dressing changes was continued. At the 3-month follow-up appointment the patient’s lesion had healed without complications.

Case #2: Cutis marmorata telangiectatica congenita

Cutis marmorata telangiectatica congenita (CMTC) is an uncommon and heterogeneous congenital vascular abnormality that can present with a broad spectrum of morphologies, distribution, and sizes.¹³ The condition closely resembles cutis marmorata, a benign and transient reticular mottling pattern of the skin that is normally seen in newborn infants secondary to dilatation of small superficial vessels in response to cold temperatures.¹⁴ It was first characterized by Van Lohuizen in 1922 and has taken many different names, including Van Lohuizen syndrome, congenital livedo reticularis, and congenital generalized phlebectasia, among others.¹⁵ Although the condition is generally benign, estimates for patients with associated abnormalities range from 20% to 80%.^14,16 CMTC is a relatively rare condition, with roughly 300 reported cases.¹⁵ However, given that the condition is often localized, heterogenous in terms of size, presents with few complications, and can ultimately regress, it is likely to be underreported.¹⁶

The pathogenesis underlying CMTC is currently unknown. One theory postulates that CMTC is due to a failure of mesodermic vessels in an early embryologic stage, while others suggest it is secondary to peripheral neural dysfunction.¹³ Teratogenic or environmental exposures might also play a role, as there have been reports of geo-temporal clustering.¹³ Many have speculated that the disease demonstrates a mosaic pattern of inheritance, as there are no reported cases of whole body involvement.¹⁶ There are also few reported familial cases, which along with the absence of whole body involvement, could be explained by the lethal gene theory.¹³ There are few established risk factors for the development of CMTC. In several case series, a slight preponderance for males has been noted, as has a tendency for infants born to fathers with increased paternal age.¹⁷ 

Clinically, the condition is characterized by the presence of persistent skin changes typical of cutis marmorata type with accompanying telangiectasias.¹⁶ Patients may also display contiguous skin atrophy or ulcerations.¹⁶ In most cases, the lesions tend to involute and can spontaneously and completely resolve later in life.¹⁶ Histologic analysis normally reveals an increase in both the number and size of capillaries and veins, but it has been shown to be inconsistent for diagnosis and is typically not necessary.^18,19 

The differential diagnosis for CMTC includes physiologic cutis marmorata, persistent cutis marmorata, reticular capillary malformations (port-wine stain), and neonatal lupus erythematous.^14,19 Physiologic cutis marmorata should regress after several weeks, and persistent cutis marmorata is a separate diagnosis seen in Down syndrome, de Lange syndrome, and homocystinuria.¹⁴ CMTC can also exist as a feature of certain syndromes; thus, a thorough history and physical should seek to evaluate for other concerning anomalies.¹⁴ Specific syndromes include: macrocephaly-CMTC syndrome (macrocephaly, CMTC, asymmetric of head, face or body, developmental delay) and Adams-Oliver syndrome (ACC, CMTC, abnormalities of hands or feet, neurologic problems).^14,17 Many patients also have associated abnormalities not consistent with named syndromes, including limb length discrepancies, hemangiomas, ocular abnormalities, cardiac malformations, hypospadias, stenotic large vessels, and café au lait spots.^14,19 

Diagnostic criteria for CMTC have been proposed and include demonstration of all 3 major criteria: (1) congenital reticular erythema; (2) absence of venectasia; (3) unresponsive to warming—and 2 or more minor criteria: (1) fading within 2 years; (2) port-wine stain or (3,4,5) ulcerations, atrophy, or telangiectasias within the affected area.¹⁴ As the disorder is self-limiting and tends to regress, treatment is generally not necessary.¹⁸ However, the clinician should have a high index for suspicion in regards to associated abnormalities. It is suggested that after an initial screen for additional anomalies, yearly follow-ups should be done for a minimum of 3 years.¹⁴

A thorough history and physical of this patient revealed no evidence of limb abnormalities, developmental delays, or other concerning features. The patient continued to be followed in the clinic with gradual improvement at each visit.

References 

1. Tincopa Wong O, Pelaez Gutierrez R, Melendez Guevara G, Paoli Razuri C, Sanchez Aznaran N. [Aplasia cutis congenita. Report of 2 cases]. Med Cutan Ibero Lat Am. 1986;14:199-204.
2. Maillet-Declerck M, Vinchon M, Guerreschi P, et al. Aplasia cutis congenita: Review of 29 cases and proposal of a therapeutic strategy. Eur J Pediatr Surg. 2013;23:89-93. doi:10.1055/s-0032-1322539.
3. Silberstein E, Pagkalos VA, Landau D, et al. Aplasia cutis congenita: Clinical management and a new classification system. Plast Reconstr Surg. 2014;134:766e-774e. doi:10.1097/PRS.0000000000000638.
4. Patel DP, Castelo-Soccio L, Yan AC. Aplasia cutis congenita: Evaluation of signs suggesting extracutaneous involvement. Pediatr Dermatol. 2018;35:e59-61. doi:10.1111/pde.13340.
5. Hioki T, Takama H, Makita S, Akiyama M. Infant bald patch: ultrasonographic diagnosis of aplasia cutis congenita. J Eur Acad Dermatology Venereol. 2017;31:e276-e277. doi:10.1111/jdv.14018.
6. Jones KM, Silfvast-Kaiser A, Leake DR, Diaz LZ, Levy ML. Adams-Oliver syndrome type 2 in association with compound heterozygous DOCK6 mutations. Pediatr Dermatol. 2017;34:e249-e253. doi:10.1111/pde.13239.
7. Humphrey SR, Hu X, Adamson K, Schaus A, Jensen JN, Drolet B. A practical approach to the evaluation and treatment of an infant with aplasia cutis congenita. J Perinatol. 2018;38:110-117. doi:10.1038/jp.2017.142.
8. Shrager S, Voin V, Iwanaga J, Tubbs RS, Johnston J. Extreme aplasia cutis congenita involving the skull. Child Nerv Syst. 2017;33:1395-1398. doi:10.1007/s00381-017-3426-x.
9. Cristina R, Sorahaya G, Angela H, Nuria P, Rosalba S, Antonio T. Aplasia cutis congenita and other anomalies associated with ­methimazole exposure during pregnancy. Pediatr Dermatol. 2011;28:743-745. doi:10.1111/j.1525-1470.2011.01572.x.
10. Kwon HS, Lee JH, Bae JM, Kim GM. Case of linear bullous aplasia cutis congenita. J Dermatol. 2017;44:e310-311. doi:10.1111/1346-8138.13972.
11. Perry BM, Maughan CB, Crosby MS, Hadenfeld SD. Aplasia cutis congenita type V: a case report and review of the literature. Int J Dermatol. 2017;56:e118-121. doi:10.1111/ijd.13611.
12. Lam J, Dohil MA, Eichenfield LF, Cunningham BB. SCALP syndrome: Sebaceous nevus syndrome, CNS malformations, aplasia cutis congenita, limbal dermoid, and pigmented nevus (giant congenital melanocytic nevus) with neurocutaneous melanosis: A distinct syndromic entity. J Am Acad Dermatol. 2008;58:884-888. doi:10.1016/j.jaad.2007.09.029.
13. Amitai D Ben, Fichman S, Merlob P, Morad Y, Lapidoth M, Metzker A. Cutis marmorata telangiectatica congenita: ­clinical findings in 85 patients. Pediatr Dermatol. 2000;17:100-104. doi:10.1046/j.1525-1470.2000.01723.x.
14. Levy R, Lam JM. Cutis marmorata telangiectatica congenita: A mimickerof a common disorder. CMAJ. 2011;183. doi:10.1503/cmaj.091749.
15. Kienast AK, Hoeger PH. Cutis marmorata telangiectatica congenita: A prospective study of 27 cases and review of the literature with proposal of diagnostic criteria. Clin Exp Dermatol. 2009;34:319-323. doi:10.1111/j.1365-2230.2008.03074.x.
16. De Maio C, Pomero G, Delogu A, Briatore E, Bertero M, Gancia P. Cutis marmorata telangiectatica congenita in a preterm female newborn: case report and review of the literature. La Pediatr Medica E Chir. 2014;36:578-583. doi:10.4081/pmc.2014.90.
17. Lapunzina P, Gairí A, Delicado A, et al. Macrocephaly-cutis marmorata telangiectatica congenita: Report of six new patients and a review. Am J Med Genet Part A. 2004;130A:45-51. doi:10.1002/ajmg.a.30235.
18. Lunge SB, Mahajan P. Cutis marmorata telangiectatica congenita restricted to both breasts in a young female. Dermatol Pract Concept. 2014;4:89-92. doi:10.5826/dpc.0403a20.
19. Van Schaik SM, Reneman L, Engelen M, Roos YBWEM, Poll-The BT. Strokelike episodes and cutis marmorata telangiectatica congenita. J Child Neurol. 2014;30:129-132. doi:10.1177/0883073813516675