|Year : 2017 | Volume
| Issue : 1 | Page : 20-22
Livedo reticularis: unfolding the enigma
Madhukara Jithendriya, Anupa M Job
Department of Dermatology, St John’s Medical College, Bangalore, India
|Date of Submission||07-Sep-2016|
|Date of Acceptance||02-Jan-2017|
|Date of Web Publication||2-Jun-2017|
Department of Dermatology, St John’s Medical College, Bangalore, 560034
Source of Support: None, Conflict of Interest: None
Livedo reticularis is a cutaneous pattern caused by the inherent anatomical and physiological property of the superficial vascular networks and in particular the larger medium-sized vessels of the subcutaneous vascular plexi. We present two cases of livedo reticularis who presented to us in a dramatically varied clinical setting, wherein the clue to diagnosis was derived upon through a simple laboratory investigation rarely ordered by a dermatologist.
Keywords: cold agglutinin, livedo reticularis, mycoplasma pneumonia
|How to cite this article:|
Jithendriya M, Job AM. Livedo reticularis: unfolding the enigma. Egypt J Dermatol Venerol 2017;37:20-2
| Introduction|| |
Livedo reticularis (LR) is a striking, macular, violaceous, net-like, patterned erythema of the skin formed by reduced blood flow and lowered oxygen tension at the peripheries of the skin segments. Although most cases of LR are considered to be a completely benign finding related to cold exposure, it may also be found secondarily to several causes such as hematological abnormalities, drugs, infections, malignancies, neurologic abnormalities, endocrine disorders, etc. We describe two cases of LR who presented to us in a dramatically varied clinical setting, wherein the clue to diagnosis was derived upon through a simple laboratory investigation rarely ordered by a dermatologist.
| Case report|| |
Patient 1 was a 58-year-old lady, a known hypertensive and dyslipidemic, on treatment and well under control, who presented to the Dermatology outpatient department with a unique complaint of repeated clotting of her blood sample in EDTA tube, obtained at room temperature in a laboratory by means of venipuncture ([Figure 1]). An initial systemic and cutaneous examination was uneventful; however, upon elicitation, Raynaud’s-like phenomenon and an erythematous-to-dusky rash in a reticular pattern were noted ([Figure 2]). Over the course of time, she developed similar rash even at 37°, which was the then temperature levels in Bangalore. In contrast, patient 2 was a 6-year-old girl, initially evaluated at a local healthcare center for fever and dry cough. Following an inexplicable fulminant deterioration of her clinical condition, she was referred to the intensive care unit of our tertiary center, for suspected sepsis with persistent fever, dry cough, hematuria, epistaxis, and jaundice. On examination, she appeared toxic with generalized LR ([Figure 3]), and at the time of examination the room temperature was kept constant at 23°C. A presumptive diagnosis of rickettsial fever was made and she was treated for the same initially at the ICU with no improvement in her clinical condition.
|Figure 1: EDTA sample of patient (a) and control (b), at room temperature.|
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Complete hemogram of both patients revealed low hemoglobin, increased total leukocyte count with neutrophil predominance, normal platelet count, and elevated erythrocyte sedimentation rate. Peripheral smears in both cases showed RBC clumping and features suggestive of autoimmune hemolytic anemia. Liver function assay showed direct hyperbilirubinemia. Renal function test and blood sugars were normal. Lactate dehydrogenase was also elevated in both. Antiphospholipid antibody and connective tissue disease work up were normal. Cryoglobulins were negative in both patients. Chest radiography and ultrasound of the abdomen and pelvis had no contributory findings. A thorough fever work up was carried out for case 2 (which included the Weil Felix test, Paul Bunnel test, Leptospira IgM assay, and peripheral smear for malaria), which were negative.
On the basis of the above clinical profile and obvious evidence of hemolytic anemia, a cold agglutinin quantitative assay was carried out, which was found to be positive even in dilutions of 1 : 2048, in both cases. Thus, in our first patient, after extensive work up a diagnosis of idiopathic (primary) cold agglutinin disease (CAD) was made and was treated accordingly. However, even in the absence of systemic symptoms, the rash was progressing over months and this triggered off the need for further investigations. A bone marrow biopsy revealed normocellular marrow with trilineage hematopoiesis and plasmacytosis, suggestive of a plasma cell dyscrasia, possibly multiple myeloma. The latter was diagnosed with CAD secondary to infection, possibly Mycoplasma pneumonia, correlating the clinical profile of the child with the high titers of cold agglutinins.
| Discussion|| |
LR is a cutaneous pattern caused by the inherent anatomical and physiological property of the superficial vascular networks and in particular the larger medium-sized vessels of the subcutaneous vascular plexi . Its occurrence with a wide range of clinical conditions, ranging from certain physiological conditions such as cutis marmorata to pathological conditions such as hypercoaguability disorders, infections, neoplasia, medications, and neurological and endocrine abnormalities , presents a diagnostic challenge. However, a systematic approach to understand the cause of LR in a patient may serve as a clue in diagnosing the primary disease, and thereby in its efficient management. CAD is a rare type of autoimmune hemolytic anemia presenting with LR . It can be classified as primary (idiopathic) or secondary (when coexisting with other diseases). When CAD is associated with infections, it tends to follow a transient course, resolving spontaneously on treating the primary illness (acute), whereas when it is found secondarily to malignancies the disease tends to be chronic . In patients with CAD, the thermal amplitude, which is defined as the highest temperature at which the antibody binds to the antigen, appears to be higher, resulting in the precipitation of hemagglutination and activation of the classical complement pathway at temperatures ranging from 28 to 31°C when compared with normal individuals with a lower thermal amplitude of about 1 to 5°C . However, temperature amplitude as high as 37° has rarely been reported. Apart from LR, other cutaneous manifestations of CAD include acral cyanosis, petechiae, and cutaneous necrosis .
Laboratory diagnosis of M. pneumonia heavily relies on the growth of the organism in culture, which may require 3 weeks or longer, as the organism is a slow grower and has fastidious growth requirements. Definitive diagnosis using serological testing requires a seroconversion documented by paired specimens obtained 2–4 weeks apart. Newer modalities such as qualitative real-time PCR assays, although promising, are not readily available, particularly in our Indian set up. A cost-effective cold agglutinin quantitative assay may aid in such a setting as in our patient with a suspected community-acquired pneumonia, as greater the cold agglutinin titer (>1 : 64), in such patients, the more likely the cold agglutinins are due to M. pneumonia ,.
Treatment is directed toward treating the cause in case of CAD associated with infections. However, those with chronic CAD require treatment with immunosuppressants such as cyclophosphamide, fludarabine, and rituximab ,. The conventional treatment for warm autoimmune hemolytic anemia with steroids is not found to be an effective option in treating CAD . The former patient, who was initially diagnosed with idiopathic (primary) CAD was treated with azathioprine 50 mg/day with intermittent steroids, with only partial response. As the thermal amplitude of the patient increased despite treatment, she was re-evaluated. Subsequently, a bone marrow biopsy revealed a plasma cell dyscrasia suggestive of multiple myeloma. She was referred to the hemato-oncologist for further management. The latter, who was diagnosed with CAD manifesting as LR and hemolysis-secondary to M. pneumonia was treated with azithromycin 500 mg once daily for 5 days and was found to have dramatic improvement systemically and resolution of LR.
| Conclusion|| |
In the two patients described in this case series, who presented to us in dramatically different clinical settings, the diagnosis was based mainly on the clinical finding of LR and a subsequent cold agglutinin titer assay. Thus:
- the need for a high index of suspicion is emphasized when dealing with a clinical sign such as LR masquerading as an occult hematological malignancy; and
- cold agglutinin assay should be used as a cost-effective modality in evaluating a patient with LR.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]